Comparison of different heparin locking frequencies in patients with unremoved catheters after continuous renal replacement therapy in the intensive care unit: a prospective, open-label, randomized controlled trial protocol from China

Abstract

Background

To investigate the impact of different heparin locking frequencies on the incidence of catheter dysfunction among patients with unremoved dialysis catheters after continuous renal replacement therapy (CRRT) in the Intensive Care Unit (ICU) of Wuhan, China. The study aims to identify a relatively low-risk locking frequency for catheter dysfunction, evaluate its effects on maintaining catheter patency and preventing catheter-related bloodstream infections (CRBSI), and determine the optimal locking strategy that balances infection risk and catheter functionality. And conduct a cost-effectiveness analysis to assess the economic value of different locking frequencies, including total medical costs.

Methods

This is a prospective, open-label, parallel-group, single-center, superiority randomized controlled trial conducted at Zhongnan Hospital of Wuhan University. A total of 390 eligible patients will be enrolled and randomly assigned in a 1:1 ratio to either the intervention group (n = 195) or the control group (n = 195). Inclusion criteria:① Patients with an unremoved dialysis catheter post-CRRT in the ICU; ② Age ≥ 18 years, regardless of gender; ③ Expected catheter indwelling time ≥ 72 h; ④ Signed informed consent by the patient or their legal representative. Exclusion criteria: ① Pre-existing catheter dysfunction or infection before enrollment; ② Actual catheter removal during the study period; ③ Participation in another interventional study within the past two months.

No stratification variables are used; simple randomization will be applied. Recruitment will be managed by the research team from the Department of Critical Care Medicine at Zhongnan Hospital of Wuhan University, including attending physicians, head nurses, and research nurses. The control group will receive heparin locking every 24 h until catheter removal, while the intervention group will be locked every 72 h. Both groups will use 1000 U/mL heparin solution (0.8 mL heparin + 4.2 mL normal saline) as the locking agent. Primary outcomes: Incidence of catheter dysfunction and catheter survival time. Safety endpoints: Rates of adverse events such as bleeding at the puncture site (persistent oozing, local hematoma), CRBSI, unplanned extubation, and air embolism. Cost-effectiveness outcomes: Total medical costs (including examination fees, treatment fees, material fees, medication fees, nursing labor costs) between the two groups. Outcome assessors and data analysts will be blinded. All analyses will follow the intention-to-treat principle based on randomized allocation, with missing data for primary outcomes excluded.

Discussion

This study represents the first prospective RCT comparing 24-h versus 72-h heparin locking frequencies in ICU patients with unremoved dialysis catheters post-CRRT. The findings are expected to provide high-quality evidence for selecting optimal catheter maintenance strategies, reducing nursing workload, and lowering healthcare costs for patients. In addition to clinical efficacy and safety, the integrated cost-effectiveness analysis will provide evidence for the economic feasibility of optimal locking strategies, supporting resource allocation decisions in clinical practice.

Trial registration {4}

Chinese Clinical Trial Registry. ChiCTR2500107820. September 1, 2025.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13063-026-09475-z.

Strengths and limitations of this study

• This is a randomized controlled trial comparing the efficacy of different catheter locking frequencies in maintaining the patency of temporarily indwelling dialysis catheters in the intensive care unit, while determining the locking frequency with a relatively lower risk of catheter dysfunction.

• This study adopts a prospective, open-label, and parallel-group design.

• This is an assessment of multiple outcomes, such as the incidence of catheter dysfunction, bleeding events (at the puncture site), the incidence of catheter-related bloodstream infections, economic benefits, length of stay in the intensive care unit or total hospital stay, and the incidence of adverse events related to CRRT catheters.

• Due to the nature of the trial, it is impossible to blind participants, clinicians, and nurses.

• This study will be conducted at a single center in central China. Although it will involve three different intensive care units, the applicability of the results to other regions and ethnic groups should still be interpreted with caution.

Protocol version {2}

Version number: V1.0

Version date: July 15, 2025

Version description: This is the initial protocol version for the study. It comprehensively outlines the study design, objectives, methods, participant eligibility, intervention details, outcome measures, statistical analysis plan, and ethical considerations.

Revision history: No revisions have been made to this protocol to date. Any subsequent modifications will be assigned a new version number (e.g., V1.1, V1.2) with a corresponding revision date and detailed description of changes. All revisions will be reviewed and approved by the Trial Steering Committee and the Ethics Committee of Zhongnan Hospital of Wuhan University before implementation, and updated information will be submitted to the Chinese Clinical Trial Registry (ChiCTR2500107820) in a timely manner.

Introduction

Background and rationale {9a}

In the intensive care unit (ICU), continuous renal replacement therapy (CRRT) is an important means of treating critically ill patients (such as those with acute kidney injury, sepsis, and multiple organ failure) [1]. After CRRT treatment, patients' dialysis catheters often need to be temporarily retained for subsequent treatment or monitoring. For example, patients may temporarily retain the dialysis catheter due to repeated illness or the need for continuous drug therapy (such as vasoactive drugs, nutritional support), so as to avoid trauma and complications caused by repeated catheterization.

Explanation for the choice of comparator {9b}

Some previous studies have explored the impact of the composition of catheter locking solutions (such as heparin concentration and antibiotic selection) on infection and thrombosis, but there has been less focus on the frequency of catheter locking [2, 3]. Two previous retrospective studies (with sample sizes of 86 and 112, respectively) reported a pooled estimated risk of catheter-related infection at 15.3%, when the locking interval was extended beyond 72 h. While this estimate reflects local clinical conditions in Chinese ICUs, the evidence level remains low due to small sample sizes and potential selection bias. [4, 5]. In China, the 24-h catheter locking protocol is commonly used in ICUs [6, 7], but in actual practice, problems such as poor compliance and strained nursing resources exist. The traditional protocol (24-h locking) can theoretically reduce the risk of infection, but frequent operations may increase the chance of contamination, the risk of catheter damage, catheter dysfunction, and the nursing burden. Some foreign scholars [8] believe that for catheters in CRRT patients, the indwelling time should not exceed 7 days if the catheter is placed in the femoral vein, and should not exceed 3 weeks if placed in the internal jugular vein or subclavian vein. Therefore, some scholars suggest that reducing the frequency of catheter locking may reduce catheter-related infections and catheter function damage caused by frequent operations. For example, with high-concentration heparin or undiluted heparin, the locking frequency can be once every 2–3 days [9, 10]. However, there is currently no high-quality research to clarify the advantages and disadvantages of the two locking frequencies, and there is a lack of unified standards in clinical practice. Essentially, there is insufficient advice and evidence to determine the locking frequency with a relatively lower risk of catheter dysfunction.

In this trial, we will compare the efficacy and safety of two catheter locking frequencies, which have drawn significant attention, on catheter function in patients with unremoved dialysis catheters after CRRT treatment in the intensive care unit.

Objectives {10}

The primary objectives of this study are: to compare the incidence of catheter dysfunction and catheter survival time between 24-h and 72-h heparin locking frequencies in patients with unremoved dialysis catheters after CRRT in the ICU. The secondary objectives are: to compare the incidence of catheter-related bloodstream infections (CRBSI), length of ICU stay, total hospitalization duration, medical costs, number of CRRT re-treatments, changes in coagulation function, rates of puncture site bleeding events, and other catheter-related adverse events (such as unplanned extubation and air embolism) between the two groups. This will allow for an evaluation of the safety and cost-effectiveness of different locking frequencies, ultimately aiming to identify the optimal strategy that balances infection risk and catheter patency.

Methods

Patient and public involvement {11}

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Trial design {12} and Trial setting {13}

This study is a prospective, open-label, parallel-group, single-center, superiority randomized controlled trial conducted at Zhongnan Hospital of Wuhan University from September 2025 to August 2026. A total of 390 eligible patients will be enrolled and randomly assigned in a 1:1 ratio to either the intervention group or the control group using a simple randomization method. It aims to compare the impact of catheter locking once every 24 h versus once every 72 h (after the initial locking at the end of CRRT treatment) on the incidence of catheter dysfunction in ICU patients with unremoved dialysis catheters after CRRT treatment. This study will be designed as a prospective, open-label, parallel-group trial. The study protocol will be developed in accordance with the Intervention Trial Checklist [11]. A flowchart of the study process is shown in Fig. 1.

Fig. 1.

Flowchart of the research process

Characteristics of the people who are needed for the trial

Table 1

Table 1.

Characteristics of the people who are needed for the trial

Characteristic	The people we would expect to see included
Age	≥ 18 years old, with no upper age limit
Sex	Male and female, no gender restrictions
Gender	Male and female
Race, ethnicity and ancestry	Han ethnicity
Socioeconomic status	No specific restrictions, covering patients with different types of medical insurance (employee medical insurance, resident medical insurance, new rural cooperative medical scheme, etc.) and self-paying patients
Geographic location	Recruitment sites: Three ICU wards in Zhongnan Hospital of Wuhan University, Wuhan City, Hubei Province, China; Study coordination site: Wuhan City, Hubei Province, China; All patients are hospitalized, without distinction between urban and rural origins
Other characteristics relevant to the trial	Patients requiring CRRT treatment with dialysis catheter indwelling time ≥ 72 h; presenting with indications for CRRT such as acute kidney injury, sepsis, multiple organ failure, etc.; without a history of catheter dysfunction or infection (prior to enrollment)

Eligibility criteria for participants {14a}

In this study, all critically ill patients in the ICU requiring CRRT support will undergo eligibility assessment. The inclusion criteria are as follows: ① Patients in the ICU whose dialysis catheters remain unremoved after CRRT treatment; ② Aged ≥ 18 years, regardless of gender; ③ Expected catheter indwelling time ≥ 72 h; ④ Informed consent signed by the patient or their family members. The exclusion criteria are as follows: ① Patients with catheter dysfunction or infection before enrollment; ② Patients whose temporary catheters are actually removed during the trial after enrollment; ③ Patients who have participated in other intervention studies within 2 months.

Eligibility criteria for sites and those delivering interventions {14b}

Eligible sites

The study is conducted at three intensive care units (ICUs) of Zhongnan Hospital of Wuhan University, which are equipped with qualified CRRT facilities, professional medical teams, and standardized clinical nursing management systems to ensure the implementation of the study protocol.

Eligibility for intervention deliverers

The research team responsible for delivering interventions consists of 2 attending physicians, 3 head nurses, and 5 specially trained research nurses from the Department of Critical Care Medicine of Zhongnan Hospital of Wuhan University. All members have received systematic training on the study protocol, including catheter locking procedures, frequency requirements, outcome assessment standards, and data collection methods, and have passed the competency assessment to ensure standardized implementation of the intervention.

Who will take informed consent? {32a}

Informed consent will be obtained by specially trained research nurses or attending physicians from the research team. Before obtaining consent, the researchers will use plain language to fully inform eligible patients or their authorized family members of the study’s purpose, specific procedures, expected benefits, potential risks, right to withdraw, and confidentiality measures. They will also answer any questions raised by the patients or their family members in detail to ensure that they fully understand the study content before voluntarily signing the written informed consent form.

Additional consent provisions for collection and use of participant data and biological specimens {32b}

The study only collects clinical data and biological specimens (such as blood samples for laboratory tests) that are necessary for outcome assessment, and all data and specimens are used exclusively for this study’s research purposes. Participants’ personal information (such as name, medical record number) will be de-identified and linked only by a unique research code to ensure data confidentiality. No additional biological specimens will be collected beyond the routine clinical tests, and no ancillary studies using the collected data or specimens will be conducted without additional informed consent. After the study is completed, the de-identified data will be stored securely in accordance with relevant regulations, and the biological specimens will be disposed of in accordance with clinical medical waste management standards or retained for future research only if additional informed consent is obtained from the participants or their legal representatives.

Intervention and comparator description {15a}

Enrolled patients will be randomly divided into two groups: ① Control group: After locking the catheter at the end of CRRT treatment, the catheter will be locked once every 24 h until the catheter is removed; ② Experimental group: After locking the catheter at the end of CRRT treatment, the catheter will be locked once every 72 h until the catheter is removed. The locking solution used in both groups is heparin 1000u/ml (0.8 ml heparin + 4.2 ml Normal Saline (NS)).

Tube sealing procedure

In this study, all inserted catheters will be temporary hemodialysis catheters. These catheters are not intended for routine blood sampling or drug administration, but solely for CRRT treatment. Vascular access will be established using 11.5 Fr (internal jugular vein)/12 Fr (femoral vein) temporary double-lumen dialysis catheters. The oXiris® or M100 hemofilter (Gambro Industries/Fresenius Medical Care) will be selected based on clinical indications. Before each treatment, the closed circuit will be pre-filled and heparinized with 1000 mL of 0.9% sodium chloride solution containing 100 mg of heparin; the blood flow rate during blood priming will be 80 ml/min, and the blood flow rate during treatment will be maintained between 120 and 150 ml/min; the specified treatment dose will be 30–35 ml/kg/hour. When the catheter is no longer needed (recovery of renal function, withdrawal of treatment, or death) or a new temporary catheter needs to be replaced (catheter dysfunction, catheter-related bloodstream infection, or catheter-related thrombosis), the attending physician and senior nurse for each patient will independently/jointly decide whether to remove the catheter.

All included patients in the intensive care unit with unremoved dialysis catheters after CRRT treatment will undergo catheter locking operations in accordance with the following procedures, as shown in Figs. 2 and 3:

Fig. 2.

Flowchart of CRRT Catheter Locking Procedure

Fig. 3.

Schematic Diagram of CRRT Catheter Locking Operation

Criteria for discontinuing or modifying allocated intervention/comparator {15b}

① If participants experience any of the above-mentioned adverse events during the study, they may withdraw from the study at any time and continue to receive appropriate symptomatic treatment. ② If participants voluntarily request to withdraw from the study during the research process, they can exit the research project and continue treatment according to their condition. ③ If participants die, are discharged from the hospital, or transferred to another department due to changes in their condition, the study will be terminated.

Strategies to improve adherence to intervention/comparator {15c}

Conduct specialized training for nurses to clarify the locking procedure and frequency requirements; use color-coded labels to differentiate groups, set electronic reminders in the nursing system to avoid omissions; verify daily locking records, conduct weekly random checks, and promptly correct non-compliant operations.

Concomitant care permitted or prohibited during the trial {15d}

Permitted concomitant care: Treatment of underlying diseases, emergency care for complications, and routine nursing (such as dressing changes and catheter disinfection); medications related to primary diseases and symptomatic treatments that comply with clinical guidelines.

Prohibited concomitant care: Unauthorized changes in locking solution or adjustments to locking frequency; using study catheters for non-CRRT purposes such as blood drawing or drug administration; using additional anticoagulant drugs without approval.

Ancillary and post-trial care {34}

All participants will receive standardized ICU routine care during the trial, including underlying disease management and catheter care (e.g., dressing changes, disinfection) per clinical guidelines; after the trial, a summary of catheter maintenance records will be provided to the clinical team to guide subsequent care. For adverse events confirmed to be directly related to the study intervention, necessary medical treatment will be promptly provided, with associated medical expenses covered by the study fund (LCHLYJ202306), and no additional financial compensation will be offered as the intervention aligns with routine clinical care risks, which will be communicated during informed consent.

Outcomes {16}

The specific details of the outcome measures in this study are presented in Table 2.

Table 2.

Outcome measures

Outcome measures	Measured Variables	Analytic Indicator	Summary Method	Time Point of Measurement	Clinical Relevance	Cut-off Value and Rationale
Primary Outcomes
Incidence of Catheter Dysfunction	Catheter function status (normal/dysfunctional)	Proportion of patients experiencing catheter dysfunction in both groups	Count data are expressed as "n (%)"	From the time of first catheter locking after CRRT completion until catheter removal or study end (whichever occurs first), daily assessments will be conducted using standardized procedures (refer to the catheter locking protocol for details)	Catheter dysfunction is one of the most common complications in patients with indwelling dialysis catheters after CRRT. It primarily manifests as poor blood flow and thrombosis, which can directly lead to interruption of subsequent treatment, increase the risk of re-catheterization and associated trauma or infection, while also exacerbating the patient's medical burden and discomfort. Therefore, it serves as a core indicator for evaluating the effectiveness of catheter locking strategies	Definition Criteria: Based on the Chinese Expert Consensus on Nursing for Critical Care Blood Purification (2021) [6] and relevant high-quality studies [12], catheter dysfunction is defined as meeting any of the following conditions: ① During non-CRRT periods: Inability to successfully aspirate 20 mL of blood within 6 s, or failure to withdraw a mixture of locking solution and blood (3–4 mL) within 1 s; ② When resuming CRRT: Inability to maintain a target blood flow rate of 120–150 mL/min, arterial pressure < − 200 mmHg, venous pressure > 200 mmHg, transmembrane pressure > 300 mmHg, or more than three pressure alarms per hour Rationale: These thresholds have been validated in multicenter clinical trials and objectively reflect catheter patency and functional status, demonstrating strong clinical applicability and feasibility
Catheter Survival Time	Duration from the first catheter locking after CRRT completion to catheter dysfunction or removal (in hours)	Distribution of catheter survival time in both groups	Survival data are presented as median (P25, P75)	The exact timings of initial catheter locking, onset of catheter dysfunction, and catheter removal will be precisely recorded	Catheter survival time directly reflects the impact of locking strategies on catheter lifespan. A longer survival duration reduces the need for re-catheterization, lowers risks of catheter-related complications such as infection and bleeding, decreases healthcare resource utilization, and provides important guidance for optimizing clinical nursing protocols	No specific cut-off value; actual survival duration will be compared between groups
Secondary Outcomes
Catheter-related bloodstream infection (CRBSI) incidence rate	CRBSI occurrence status (yes/no)	Proportion of patients with confirmed CRBSI in both groups	Count data are expressed as "n (%)"	Daily monitoring during the trial period until 48 h after catheter removal (high-risk window for CRBSI)	Catheter-related bloodstream infection (CRBSI) is one of the most serious complications associated with indwelling vascular catheters. It can lead to severe consequences such as sepsis and multiple organ failure, significantly increasing patient mortality and length of hospital stay, making it a key indicator for assessing the safety of catheter locking strategies	Definition Criteria: In accordance with the Guidelines for Prevention and Control of Catheter-Related Infections (2021) [13], catheter-related bloodstream infection (CRBSI) is defined as isolation of the same pathogen from both catheter tip culture and at least one peripheral blood culture within 48 h after catheter removal, with identical antimicrobial susceptibility profiles, while excluding other identifiable sources of infection Rationale: This definition represents a standardized criterion in domestic clinical infection control, enabling precise differentiation between catheter-related and non-catheter-related bloodstream infections, thereby ensuring objectivity in outcome assessment
Length of ICU Stay	Duration from ICU admission to ICU discharge (in days)	Length of ICU stay in both groups	Continuous data with non-normal distribution are presented as median (P25, P75)	Record dates of ICU admission and transfer out, then calculate duration	Length of ICU stay serves as a comprehensive measure reflecting disease severity and treatment efficacy. By influencing the incidence of catheter-related complications, locking strategies indirectly affect how long patients remain in the ICU. This data provides valuable insights for optimizing healthcare resource allocation	No specific cut-off values; actual length of ICU stay will be compared between groups
Total Length of Hospital Stay	Duration from hospital admission to hospital discharge (in days)	Total length of hospitalization in both groups	Count data, expressed as "n (%)" (stratified by event occurrence) and mean ± standard deviation for normally distributed data	Record dates of hospital admission and discharge, then calculate duration	Total hospitalization duration directly correlates with medical costs and patient outcomes. Comparing this metric between groups allows evaluation of how locking strategies impact overall treatment progress, highlighting the health economic value of the study	No specific cut-off values; actual total hospitalization duration will be compared between groups
Medical Expenses	Total medical costs related to the current illness during hospitalization (in CNY), including examination fees, treatment fees, material fees, medication fees, etc	Total medical costs and breakdown of expenses in both groups	Continuous data: normally distributed variables are shown as mean ± standard deviation; non-normally distributed variables are reported as median (P25, P75)	Extract and summarize medical cost details from the inpatient billing system upon patient discharge	Medical expenses are a core component of health economic evaluations. Differences in costs between the two locking frequencies can inform clinical decisions toward cost-effective care strategies, thereby reducing financial burden on both patients and insurance systems	No specific cut-off values; actual medical costs will be compared between groups
Number of Re-administrations of CRRT	Number of additional CRRT treatments received by the patient from enrollment until discharge or study end	Distribution and mean number of additional CRRT treatments in both groups	Count data are expressed as "n (%)"	Document each instance of CRRT initiation until hospital discharge or study completion	The number of additional CRRT treatments reflects renal recovery and clinical stability. By maintaining catheter patency, effective locking strategies reduce treatment interruptions or re-initiation needs, indirectly demonstrating better disease control	No specific cut-off values; actual number of additional CRRT treatments will be compared between groups
Coagulation Function	Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-dimer (D-Dimer)	Changes in coagulation function parameters from baseline to the end of the study in both groups	Count data are expressed as "n (%)"	Assessed at baseline (pre-randomization), every 3 days during the trial, and until catheter removal	Both groups use heparin-based locking solutions; thus, changes in coagulation parameters directly reflect heparin’s effect on hemostasis. Monitoring these markers helps determine whether frequent locking increases bleeding risk, providing critical safety data for strategy implementation	No specific cut-off values; actual coagulation function parameters will be compared between groups
Incidence of Catheter Adverse Events	Occurrence status of unplanned extubation and air embolism (yes/no)	Proportion of patients experiencing the aforementioned adverse events and overall incidence rates in both groups	Continuous data with non-normal distribution are presented as median (P25, P75)	Continuous real-time surveillance and documentation throughout the trial until catheter removal	Unplanned extubation and air embolism represent severe adverse events linked to catheter management, potentially leading to clinical deterioration or death. Their occurrence rates serve as important indicators of procedural safety and nursing quality	Unplanned extubation: Defined according to the Critical Care Nursing Practice Guidelines as catheter dislodgement due to patient self-action or accidental causes without healthcare provider approval, or premature removal due to catheter dysfunction or other unintended reasons Air embolism: Diagnosed based on clinical symptoms (e.g., dyspnea, chest pain, altered consciousness) combined with imaging confirmation
Bleeding Events at the Puncture Site	Occurrence status of persistent oozing at puncture site and local hematoma (yes/no)	Proportion of patients with bleeding events in both groups	Count data, expressed as "n (%)" (stratified by event occurrence) and mean ± standard deviation for normally distributed data	Monitored post-each locking procedure and during daily assessments until catheter removal	Bleeding at the puncture site is a common safety endpoint related to heparin locking. Frequent locking may elevate local trauma risk; comparing incidence between groups helps evaluate the advantage of less frequent locking in minimizing hemorrhagic complications	Persistent oozing: Defined as bleeding at the puncture site lasting > 10 min post-locking procedure, or spontaneous oozing persisting > 24 h under normal conditions Local hematoma: Defined as subcutaneous hematoma at the puncture site with diameter > 2 cm, or progressive enlargement of the hematoma Rationale: These criteria are derived from the Standards for Intravenous Therapy Nursing Techniques [14], allowing objective distinction between minor bleeding and clinically significant hemorrhagic events
Reasons for Catheter Removal	Specific reasons for catheter removal (renal function recovery, catheter dysfunction, CRBSI, patient discharge, death, other)	Composition ratio of various reasons for catheter removal in both groups	Continuous data: normally distributed variables are shown as mean ± standard deviation; non-normally distributed variables are reported as median (P25, P75)	Reasons for catheter removal are jointly recorded by attending physician and senior nurse at time of removal	Analyzing the distribution of reasons for catheter removal indirectly reflects the effectiveness of each locking strategy in preserving catheter function and reducing infection risks, offering evidence-based guidance for optimizing catheter maintenance practices	No specific cut-off values; actual reasons for catheter removal will be analyzed and compared between groups
Medical Expenses	Nursing labor cost for catheter locking care (calculated as: locking frequency × average time per procedure × nursing hourly rate); Other direct medical costs (including expenses for locking consumables, treatment of adverse events, hospitalization fees, etc.)	Mean nursing labor cost for catheter locking care and mean total medical costs in both groups;	Nursing labor cost and total medical costs: Data with non-normal distribution are presented as "median (P25, P75)"	Catheter locking care time: The duration of each locking procedure was recorded in real time after every session and used to calculate nursing labor costs based on the frequency of locking and the hospital’s standard hourly nursing rate (as defined by the department) Total medical cost: Summarized from the hospital billing system upon patient discharge, with detailed breakdowns for adverse event-related treatments also calculated accordingly	The nursing labor cost for catheter locking care is a core component of the cost-effectiveness analysis, directly reflecting differences in resource consumption between the two locking frequencies (24-h vs. 72-h). By integrating total medical costs with health outcomes (measured as QALYs), this approach enables precise quantification of the economic value of different locking strategies, thereby providing robust data to support clinical decisions toward "high-efficiency and low-consumption" nursing protocols	There is no specific cutoff value; the cost-effectiveness of catheter removal in each group will be analyzed and compared

Harms {17}

During the clinical research on patients, the following adverse events may occur:

• (1) Persistent bleeding at the puncture site: Use sterile gauze or cotton balls to press vertically above the puncture point (proximal end) with a force sufficient to effectively block blood flow for 5–10 min. In case of arterial bleeding, the pressing time needs to be extended to more than 15 min. At the same time, depending on the specific situation, blood routine tests and transfusion of red blood cell suspension, platelets or other blood products should be performed if necessary.

• (2) Catheter-related bloodstream infection (CRBSI): Once CRBSI is suspected, all intravascular catheters will be removed as soon as possible unless there are absolute contraindications (such as being completely dependent on the access to maintain life without alternative options). The catheter tip and subcutaneous segment will be retained for quantitative culture to confirm the diagnosis. If the patient is hemodynamically unstable or a new access cannot be established immediately, the catheter can be temporarily retained but the dressing should be replaced after strict disinfection, and empirical anti-infection treatment should be initiated simultaneously. Meanwhile, antibiotic anti-infection treatment should be administered if necessary according to the situation.

Participant timeline {18}

These data will be collected throughout the study period, and the data collection time is shown in Table 3.

Table 3.

Schedule of Trial Data Collection (Participant timeline)

	Study phase
	Recruitment	Baseline assessment	Allocation	Intervention	Outcome evaluation
TIMEPOINT	-t1	t0			t1
ENROLMENT
Eligibility screening	X
Informed consent	X
Random grouping
Allocation			X
Interventions
24-h catheter locking				X
72-h catheter locking				X
Assessment
Demographics and medical history		X
Disease treatment-related information		X
Laboratory test results		X
Catheter dysfunction				X	X
Catheter survival time					X
Length of ICU stay					X
Total length of hospital stay					X
Medical expenses					X
Number of re-administrations of CRRT					X
Changes in coagulation function					X
Catheter adverse events (unplanned catheter slippage, air embolism)				X	X
Bleeding events (at the puncture site)				X	X
Catheter-related bloodstream infection				X	X
Reasons for catheter removal					X
Cost-effectiveness		X		X	X

CRRT Continuous Renal Replacement Therapy

Sample size {19}

As stated in the preface, frequent operations may increase the risk of contamination, catheter damage, catheter dysfunction, and nursing burden. Since the incidence of intravascular catheter-related infections is extremely low in clinical practice, a very large sample size would be required to provide evidence for it. To ensure the conduct of the study, we have chosen catheter dysfunction as the primary outcome measure. Therefore, our hypothesis is that the 72-h catheter locking frequency group has a significantly better effect in reducing the incidence of catheter dysfunction compared with the 24-h catheter locking frequency group among ICU patients whose dialysis catheters remain unremoved after CRRT treatment. Based on previous studies [12] and our clinical experience, we used the 21% incidence of catheter dysfunction reported in the literature as the incidence of catheter dysfunction in the control group. In addition, prior to this trial, we conducted a pilot study and found that the incidence of catheter dysfunction was 11.1% when using the 72-h catheter locking frequency. We performed the sample size calculation using G-Power V.3.1 [15] with an α value of 0.05 and a power of 80%. Therefore, we need a total of 354 participants (177/group). Considering a potential 10% loss rate, we determined that 390 participants should be recruited for this study (195/group).

Recruitment {20}

Recruitment Scope: Three ICUs in Zhongnan Hospital of Wuhan University, screening eligible patients who retain dialysis catheters after CRRT.

Recruitment Method: The research team screens patients daily, explains the study to eligible individuals or their families, and obtains informed consent.

Timeline: Recruitment will begin on September 1, 2025, with enrollment of 390 cases completed by August 2027, and monthly progress monitoring.

Avoiding Duplication: Verification through electronic medical records ensures that patients have not participated in other intervention studies within two months.

Assignment of interventions: randomization

Sequence generation {21a} and type of randomisation {21b}

Patients who meet the inclusion and exclusion criteria will be randomly assigned to the experimental group or the control group in a 1:1 ratio using the statistical software SPSS V.23.0 based on the principle of simple randomization to generate a random number table.

Allocation concealment mechanism and implementation {22} and Implementation {23}

The generated random sequence will be sealed in opaque envelopes, which will be safely stored by the project leader and distributed to the research implementers after registration.

Who will be blinded {24a}, How will be blinding be achieved {24b}, Procedure for unblinding if needed {24c}

Not applicable. This study is an open-label trial, where participants, clinicians, and nurses cannot be blinded, and there is no "unblinding" scenario, so it is not applicable.

Plans for assessment and collection of outcomes {25a}

All baseline assessments will be completed before randomization to ensure objective and balanced baseline data, including three categories of information collected via standardized methods: ① General personal data: age (years), gender (Male/Female), body mass index (BMI, kg/m²), Acute Physiology and Chronic Health Evaluation score (APACHE II, 0–71 points; higher scores indicate more severe condition), Sequential Organ Failure Assessment score (SOFA, 0–24 points; ≥ 15 points suggest poor prognosis), age-adjusted Charlson Comorbidity Index (aCCI, 0–37 points; higher scores indicate greater comorbidity burden), mechanical ventilation status (Yes/No), and comorbidities (Hypertension/Diabetes Mellitus/Coronary Heart Disease/Malignant Tumor); ② Disease treatment-related information: reasons for CRRT initiation (Acute kidney injury/sepsis/multiple organ failure/severe electrolyte disturbance/other), CRRT vascular access placement site (internal jugular vein/femoral vein/subclavian vein), history of surgery within three months before CRRT (Yes/No), CRRT anticoagulation method (unfractionated heparin/low molecular weight heparin/citrate/nemostat/no anticoagulation), CRRT initiation time, and duration of the first CRRT treatment (hours); ③ Laboratory test results: creatinine (μmol/L), blood urea nitrogen (mmol/L), hemoglobin (g/L), platelets (× 10⁹/L), hematocrit (%), coagulation time (s), total calcium (mmol/L), pH value, procalcitonin (ng/mL), and lactic acid (mmol/L). Outcome indicators (e.g., catheter dysfunction, CRBSI, coagulation function changes) will be collected per the predefined time points using standardized assessment tools and electronic medical record extraction, with outcome assessors blinded to group allocation to ensure data accuracy.

Plans to promote participant retention and complete follow-up {25b}

To ensure full follow-up of participants until catheter removal or study end, the following measures will be implemented: ① Assign dedicated research nurses to track each participant’s progress, conduct daily checks on catheter status and outcome indicators, and record data in real time to avoid omissions; ② For participants transferred within the hospital or discharged early, the research team will coordinate with the receiving department or follow up via medical record review to complete outcome data collection; ③ Regularly communicate with the clinical team to timely grasp participants’ condition changes (e.g., death, withdrawal of treatment) and record relevant information as required; ④ Establish a standardized data tracking system, with the principal investigator conducting weekly reviews to identify and address follow-up obstacles promptly; ⑤ For participants who withdraw voluntarily, the research team will document the reason for withdrawal and collect available outcome data up to that point to maximize data completeness.

Data management {26}

The implementers of this study are responsible for data collection and entry, and the principal investigator is responsible for data review, monitoring, and storage.

Confidentiality {33}

All personal and clinical data of participants will be de-identified with unique research codes, and stored securely in password-protected systems accessible only to the research team. Paper records (if any) will be kept in locked cabinets, and data will not be disclosed to third parties without authorization. After the study, data will be retained in accordance with regulatory requirements to ensure privacy protection throughout the process.

Statistical methods

All analyses will be performed using SPSS 23.0 (IBM Corp., Armonk, NY, USA). The statistical analysis of this study will strictly adhere to the research objectives, employing appropriate statistical methods for primary and secondary outcome measures as detailed below:

Statistical methods for primary and secondary outcomes {27a}

Primary Outcome Measures Analysis: ①Catheter Dysfunction Rate: The χ² test will compare differences between groups, calculating risk ratios (RR) and 95% confidence intervals. ②Catheter Survival Time: Kaplan–Meier method will plot survival curves, log-rank test will compare inter-group differences, and Cox proportional hazards regression model will analyze the association between locking frequency and catheter dysfunction onset time.

Secondary Outcome Measures Analysis: ①Count Data (e.g., CRBSI incidence, adverse event rates) will undergo inter-group comparisons via χ² test or Fisher's exact test, calculating RR and 95% confidence intervals. ②Continuous Data (e.g., ICU length of stay, total hospitalization time, medical expenses) will be compared using independent samples t-test or rank-sum test based on distribution type. ③Coagulation Function Changes: Repeated measures ANOVA will compare coagulation function indicators (prothrombin time, activated partial thromboplastin time, etc.) at different time points between groups.

Analysis population {27b}

An Intention-to-Treat (ITT) principle will be adopted, including all patients randomly assigned to either the intervention or control group in the primary analysis. Samples with missing data for the primary outcome measure will be excluded, while missing data for secondary outcome measures will be handled using corresponding methods (see "Handling of Missing Data {27c}" below).

Handling of Missing Data {27c}

①For primary outcome measures, complete case analysis will be used. ②For secondary outcome measures, if missing rate < 20%, multiple imputation (generating 5 imputed datasets, pooling results) will be employed. If missing rate ≥ 20%, missing status will be described, and sensitivity analysis will assess impact.

Methods for additional analyses {27d}

Baseline Descriptive Statistics: ①Categorical variables (e.g., gender, types of comorbidities, CRRT anticoagulation methods) will be presented as numbers (%). Group comparisons will use the χ² test or Fisher's exact test. ②Continuous variables with normal distribution (e.g., age, BMI, APACHE II score) will be expressed as mean ± standard deviation (mean ± SD). Inter-group comparisons will use independent samples t-test, and intra-group comparisons will use paired t-test. ③Continuous variables with non-normal distribution (e.g., ICU length of stay, total hospitalization time, medical expenses) will be reported as medians (P25, P75). Group comparisons will use the rank-sum test.

Confidence intervals

95% confidence intervals will be provided for all primary outcome measures (catheter dysfunction rate, catheter survival time) and key secondary outcome measures (CRBSI incidence, occurrence rate of puncture site bleeding events, etc.) to enhance result reliability and clinical interpretability.

Multiple comparisons handling

To control Type I error due to multiple secondary outcome measures, Bonferroni correction will be applied. The adjusted α level is set at 0.05/9 = 0.0056 (for 9 secondary outcomes), determining statistical significance for inter-group differences.

Adverse event reporting

Adverse events will be categorized by type (puncture site bleeding, CRBSI, unplanned extubation, etc.), calculating incidence, timing, and severity per group. Descriptive statistics will present results, with inter-group comparisons using χ² test or Fisher's exact test.

Cost-effectiveness analysis

A cost-effectiveness analysis will be conducted from the healthcare system perspective. Direct medical costs will be extracted from the hospital’s inpatient billing system, including detailed breakdowns of CRRT-related consumables, heparin locking materials, nursing labor costs (calculated based on locking frequency and time per operation), examination fees (e.g., coagulation function tests, infection screening), treatment costs for adverse events (e.g., CRBSI anti-infection therapy, bleeding management), and hospitalization expenses (ICU and general ward stays). Subcomponent costs—including nursing labor cost for catheter locking care, expenses for locking consumables, and treatment costs for adverse events—are described using "median (P25, P75)" to reflect their distribution characteristics, consistent with the reporting of total medical costs. This approach is adopted because healthcare cost data typically exhibit non-normal distributions. Between-group comparisons were performed using the Mann–Whitney U test (a rank-sum test) to analyze differences in both subcomponent costs and total medical costs between the two groups.

Interim analyses {28b}

An interim analysis will be conducted by the Data Monitoring Committee when half of the recruitment is completed (195 cases). The focus will be on evaluating the primary outcome measure (the incidence of catheter dysfunction) and the incidence of serious adverse events. If differences between the two groups reach a preset threshold or serious safety risks arise, they shall be reported as required and the research protocol adjusted accordingly.

Protocol and statistical analysis plan {5}

The complete trial protocol has been integrated into this report, covering the study design, objectives, interventions, and oversight. The statistical analysis plan (SAP) is also detailed in {27d}. Subsequent revisions to the SAP will be documented, approved by the trial steering committee, made publicly available, and reported to the ethics committee and clinical trial registry. The final SAP will be publicly accessible via the Chinese Clinical Trial Registry after the study's completion.

Oversight and monitoring

Composition of the coordinating centre and trial steering committee {3d}

A Trial Steering Committee was established for this study, consisting of five members. Among them, three are independent members (not involved in the implementation or data collection of this study): A professor from the Department of Critical Care Medicine at Zhongnan Hospital of Wuhan University (primarily responsible for reviewing the scientific validity of the trial design); A professor of statistics from the School of Public Health at Wuhan University (primarily responsible for reviewing the statistical analysis plan); An ethics expert from the Zhongnan Hospital Medical Ethics Committee at Wuhan University (primarily responsible for overseeing the ethical aspects of the trial). The remaining two members are core members of the research team (corresponding authors: Professor Zhao Xiangyang and Professor Jin Li), who are responsible for coordinating the progress of the trial. The committee meets every three months to review the trial progress, data quality, adverse events, and other relevant matters, ensuring the scientific rigor and ethical compliance of the study.

Composition of the data monitoring committee, its role and reporting structure {28a}

The Data Monitoring Committee, composed of the Ethics Committee and the Scientific Research Department of Zhongnan Hospital of Wuhan University, is in charge of data monitoring, interim review, and final review to ensure the quality of research data. In addition, all adverse events are recorded in detail, properly handled, and followed up until they are properly resolved or the patient's condition is stable.

Frequency and plans for auditing trial conduct {29}

Serious adverse events and unanticipated events are reported to the Ethics Committee and the competent authorities (Medical Affairs Department, Nursing Department) in a timely manner in accordance with regulations (in 24 h). The principal investigator regularly conducts cumulative reviews of all adverse events and, if necessary, convenes investigator meetings to assess the risks and benefits of the study.

Protocol amendments {31}

Protocol amendments must be proposed by the investigator, stating the reasons for revision, content details, and impact on the study. Amendments can only be implemented after review by the trial steering committee and approval from the ethics committee. Revised content will be promptly updated in research documents, communicated to all researchers, and reported to the clinical trial registry as required.

Dissemination policy {8}

The results of this trial will be presented at domestic and international scientific conferences, and the final manuscript will be published in peer-reviewed journals.

Discussion

The most challenging aspect during the implementation of the trial is that the dropout rate in the 72-h group will be very high. Based on previous clinical experience, we have found that only patients with acute kidney injury or sepsis may undergo CRRT treatment multiple times, but the interval between treatments may be interrupted due to changes in the patient's condition. Therefore, we may need to conduct comprehensive communication and cooperation with multiple ICU wards to include as many required samples as possible. The principal researchers will regularly monitor the progress of participant enrollment, compliance with the study protocol, and the overall progress of the research, and make appropriate adjustments according to the actual situation of the study.

This study is scientific, innovative, and feasible. To our knowledge, this will be the first prospective, randomized controlled trial to compare the impact of 24-h and 72-h catheter locking frequencies on the incidence of catheter dysfunction in patients whose dialysis catheters remain unremoved after CRRT treatment in the intensive care unit. It will also evaluate the effects of different catheter locking frequencies on maintaining catheter patency and catheter-related bloodstream infections, aiming to identify a catheter locking strategy that can better balance the risk of infection and the maintenance of catheter patency. We hope that the results of the trial will support the selection of catheter locking frequencies for patients with unremoved dialysis catheters after temporary CRRT treatment and the development of future catheter care. Ultimately, it will reduce the nursing burden and the cost for patients.

However, there are still some limitations of this trial that need to be considered. First, due to the nature of the intervention and practical considerations, patients, clinicians, and nurses will not be blinded during the study. Nevertheless, we will carefully design our recruitment, randomization, allocation, outcome assessment, data collection, and analysis methods to minimize bias. Second, this study will be conducted in central China, and the catheter maintenance methods may be inconsistent with those in other regions of China or the world. This means that the research results need to be interpreted cautiously with regard to regional differences. In the future, we will further expand the study to more regions to verify our research findings.

Trial Status

This study is currently underway. Patient recruitment commenced on September 1, 2025, and is ongoing. It is projected to complete all recruitment by August 2027.

Authors’ contributions {3a}

Yanting Zhang, Jing Ma, Chang Liu, Zhaoyang Li, Jin Li and Xinbo Ding designed the trial. Yanting Zhang and Jing Ma drafted the manuscript. Zhaoyang Li, Jin Li and Xinbo Ding provided critical revision of the manuscript. Other authors also participated in the discussions and assisted in improving the research plan. They also carefully reviewed and approved the final paper manuscript.

Funding {7a}

This study was supported by the Clinical Nursing Research Program of Zhongnan Hospital of Wuhan University in 2023 (LCHLYJ202306).

Data availability {6}

The data sets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate {30}

This study will adhere to relevant regulations such as the Declaration of Helsinki of the World Medical Association and the Methods for Ethical Review of Biomedical Research Involving Humans issued by the National Health and Family Planning Commission of the People's Republic of China. It has been approved by the Medical Research Ethics Committee of Zhongnan Hospital of Wuhan University (approval number: 2025199 K) and registered at the Chinese Clinical Trial Registry with the registration number: ChiCTR2500107820. Before each participant is enrolled in the study, researchers will fully and comprehensively inform the participant or their agent of the purpose, procedures, and potential risks of the study. A written informed consent form will be signed, and participants will be informed that their participation is entirely voluntary, they have the right to withdraw from the study at any time without facing any bias, and their medication, care, and rights will not be affected. During the study, the personal privacy and data confidentiality of the subjects will be protected, and access to such information will be restricted to the research team only.

Consent for publication

Not Applicable. The study focuses on comparing clinical intervention effects and analyzing anonymized clinical data, with no individual participant’s identifiable information, personal images, or sensitive private content included in the planned publication. All data used for reporting will be de-identified and aggregated, so specific consent for publication from participants or their legal representatives is not required.

Competing interests {7b}

The authors report no conflicts of interest in this work.