Endotracheal Tube Repositioning Frequency for Preventing Oral Mucosal Pressure Injuries in Intensive Care Units: A Randomised Controlled Trial Study Protocol

ABSTRACT

Background

Endotracheal tubes (ETTs) exert sustained pressure and friction on the oral mucosa, placing mechanically ventilated intensive care unit (ICU) patients at increased risk of mucosal membrane pressure injuries (MMPIs).

Aim

To compare the effect of 4‐h and 8‐h ETT repositioning intervals on the prevention of oral MMPIs in adult ICU patients receiving invasive mechanical ventilation (MV).

Methods

This study is designed as an analyst‐blinded, parallel‐group randomised controlled trial. Adult ICU patients receiving invasive MV via an oral ETT and with Acute Physiology and Chronic Health Evaluation System (APACHE II) scores ≤ 24 will be randomised (1:1) to either 4‐h or 8‐h ETT repositioning intervals, with stratification by APACHE II score (≤ 20 and 21–24). The primary outcome is the development of oral MMPIs during a 14 day follow‐up period or until extubation, tracheostomy, transfer or death, assessed using the Reaper Oral Mucosa Pressure Injury Scale–TR. Secondary outcomes include the timing, severity, and anatomical location of MMPIs.

Results

The primary hypothesis is that a 4‐h ETT repositioning interval will significantly reduce the incidence of oral MMPIs compared to an 8‐h interval. It is anticipated that more frequent repositioning will better preserve mucosal integrity and improve patient comfort. These results are expected to provide evidence‐based guidance for standardizing nursing‐led ETT care protocols in ICU.

Relevance for Clinical Practice

By examining ETT repositioning intervals in relation to disease severity, this study may support more standardised and patient‐centred preventive strategies and contribute to safer, more efficient nursing care in intensive care settings.

Trial Registration

The Clinical Trial Registration number (Unique Protocol ID) is NCT07390162.

Impact Statement

• What is known about the topic

  • ○
    Endotracheal tube (ETT)‐related oral mucosal membrane pressure injuries (MMPIs) are a significant patient safety concern in intensive care units (ICUs), with incidence rates reported as high as 49%.
  • ○
    International guidelines recommend regular repositioning of medical devices to prevent PIs, but they do not provide specific, evidence‐based intervals for ETT repositioning.
  • ○
    Current ETT repositioning practices in ICUs are often inconsistent and largely based on local nursing routines or expert consensus rather than high‐quality clinical trial data.
• What this paper adds

  • ○
    This study protocol outlines what is, to the best of our knowledge, among the first randomised controlled trials to directly compare the efficacy of 4‐h versus 8‐h ETT repositioning intervals in preventing oral MMPIs.
  • ○
    By integrating APACHE II‐based stratification, the study examines how disease severity modifies the effectiveness of repositioning frequency, supporting a more individualised approach to nursing care.
  • ○
    The findings will provide robust evidence to help standardise ICU nursing protocols, potentially balancing patient safety with nursing workload by identifying optimal, evidence‐based repositioning schedules.

Abbreviations

APACHE II

Acute Physiology and Chronic Health Evaluation II

DRPI

Device‐Related Pressure Injury

ETT

Endotracheal Tube

ICU

Intensive Care Unit

MDRPI

Medical Device‐Related Pressure Injury

MMPI

Mucosal Membrane Pressure Injury

MV

Mechanical Ventilation

OAG

Oral Assessment Guide (Eilers')

PI

Pressure Injury

RASS

Richmond Agitation‐Sedation Scale

ROMPIS

Reaper Oral Mucosa Pressure Injury Scale

1. Introduction

Intensive care units (ICUs) rely heavily on medical devices for life support; however, medical device‐related pressure injuries (MDRPIs), particularly mucosal membrane pressure injuries (MMPIs), remain a significant patient safety concern [1, 2, 3]. These injuries are associated with substantial clinical consequences, including pain, infection risk and prolonged recovery [4, 5, 6, 7, 8, 9, 10, 11]. Among them, endotracheal tube (ETT)‐related oral injuries are common, early‐onset complications in mechanically ventilated patients, yet evidence‐based prevention strategies, particularly regarding repositioning frequency, remain limited [12, 13, 14, 15, 16].

1.1. Background

MDRPIs constitute a substantial proportion of all pressure injuries in ICU patients, with reported incidence ranging widely from 0.9% to 59.1%, of which 15.3%–63.7% involve mucosal tissues [4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]. Endotracheal tubes (ETTs) are a major contributor to oral MMPIs due to sustained pressure and friction on vulnerable mucosal surfaces, with reported incidence rates between 7% and 49% [12, 13, 14, 15, 16]. These injuries often develop early during mechanical ventilation and are associated with pain, infection risk, increased workload and reduced patient comfort [17, 18, 19, 20, 21].

The development of oral MMPIs is multifactorial. Disease severity, reflected by APACHE II and SOFA scores, has been consistently associated with increased risk [7, 12, 22]. Additional intrinsic and extrinsic factors including haemodynamic instability, nutritional status, vasopressor use, ETT fixation method, oral care frequency and repositioning intervals further contribute to mucosal vulnerability [17, 23, 24, 25, 26, 27, 28].

Among modifiable factors, ETT repositioning frequency represents a key nursing intervention. Although international guidelines recommend regular device repositioning, they provide limited evidence‐based guidance regarding optimal intervals for ETT management [3, 29]. Existing recommendations are largely based on expert consensus, and empirical evidence remains scarce. A limited number of studies suggest that more frequent repositioning may reduce MMPI incidence; however, these findings are not derived from robust randomised controlled trials [30, 31, 32, 33].

In clinical practice, ETT repositioning is often guided by local routines rather than standardised protocols, resulting in variability in care delivery [27]. Furthermore, no previous randomised studies have examined whether repositioning frequency should be adapted according to disease severity [3, 12, 13, 16, 21, 29, 30, 34].

Therefore, this study aims to evaluate the effect of two clinically relevant ETT repositioning intervals (4‐h vs. 8‐h) on oral MMPIs prevention, while incorporating APACHE II‐based stratification to explore potential differences according to patient severity.

1.2. Aim

The primary aim of this study is to evaluate the effect of 4‐h versus 8‐h ETT repositioning intervals on the prevention of oral MMPIs in adult ICU patients receiving invasive mechanical ventilation. Secondary aims include identifying the anatomical locations of MMPI development (e.g., upper lip, lower lip and oral commissures) and examining whether the effect of repositioning frequency varies according to disease severity, stratified by APACHE II score subgroups (≤ 20 and 21–24).

1.3. Originating Hypotheses of the Study

Hypothesis 1

The incidence of oral MMPIs differs between patients receiving 4‐h and 8‐h ETT repositioning in the ICUs.

Hypothesis 2

The effect of ETT repositioning frequency on oral MMPIs development differs according to disease severity, stratified by APACHE II score subgroups (≤ 20 vs. 21–24).

2. Methods

2.1. Design

This study follows Consolidated Standards of Reporting Trials (CONSORT) guidelines [35] and is designed as a two‐arm, parallel‐group, analyst‐blinded randomised controlled trial comparing 4‐ and 8‐h ETT repositioning intervals (File S1). Participants will be allocated (1:1) using stratified randomisation based on APACHE II score (≤ 20 vs. 21–24).

2.2. Setting

The study will be conducted in three tertiary anaesthesia ICUs of a training and research hospital in Ankara, Türkiye, between May 2026 and January 2028. Units have similar organisational structures (Table 1).

TABLE 1.

Structural and clinical characteristics of the intensive care units.

Intensive care clinic	Bed capacity	Number of nurses
Anaesthesia ICU (Block B)	2 isolation–8 standard beds	20 nurses
Anaesthesia ICU (Block H)	2 isolation–10 standard beds	24 nurses
Anaesthesia ICU (Block K)	4 isolation–10 standard beds	28 nurses

Abbreviation: ICU, intensive care unit.

All nurses who implemented the intervention in the study were registered nurses holding a bachelor's degree and having at least 1 year of experience in an ICU; this ensures consistency in the implementation of the study intervention. Nursing organisation follows a total patient care model with a standardised nurse‐to‐patient ratio of 1:2.

2.3. Participants

2.3.1. Inclusion Criteria

Patients will be eligible for inclusion if they meet all of the following criteria:

• age ≥ 18 years;

• receiving invasive MV via an oral ETT;

• absence of tissue loss or PI in the oral mucosa at the time of ICU admission;

• duration of endotracheal intubation ≤ 24 h at the time of enrolment;

• APACHE II score ≤ 24;

• provision of written informed consent by a first‐degree relative or legal representative.

2.3.2. Exclusion Criteria

Patients meeting any of the following criteria will not be included in the study:

• Non‐invasive respiratory support: Patients receiving non‐invasive MV support via face mask or nasal cannula (CPAP or BiPAP), as ETT‐related mucosal pressure does not occur.

• Pre‐existing artificial airway: Patients with a tracheostomy prior to study enrolment due to anatomical differences and the inability to apply standard ETT securement methods.

• Oncological conditions: Patients receiving active chemotherapy, due to increased mucositis risk and impaired tissue healing.

• Neurological and behavioural factors: Patients with recurrent seizures, an uncontrolled biting reflex or those who bite the ETT, as these increase the risk of mechanical trauma.

• Positional constraints: Patients managed in the prone position as this limits standard ETT securement and mucosal assessment.

• Severe neurological impairment: Patients with conditions significantly affecting pain perception and tissue response.

• Pre‐existing mucosal injury: Patients with oral MMPIs of Stage 2 or higher at baseline assessment.

2.3.3. Withdrawal Criteria

Patients will be withdrawn from the study under the following circumstances:

• Withdrawal of consent: The patient's legal representative withdraws consent after enrolment.

• Airway change: The patient is extubated or converted to tracheostomy during follow‐up, as the intervention is no longer applicable.

• Transfer or death: The patient dies or is transferred to another unit/hospital before completion of the follow‐up period.

• Protocol non‐adherence or incomplete data: Due to clinical circumstances (e.g., emergency surgery and prolonged imaging), two consecutive interventions cannot be performed, or essential physiological data are missing.

2.4. Recruitment

Eligible patients will be consecutively screened at ICU admission. Written informed consent will be obtained from legal representatives prior to enrolment. Patients regaining capacity will provide confirmatory consent. Participants will be followed for up to 14 days or until extubation, tracheostomy, transfer or death.

2.5. Standard Care and Intervention

2.5.1. Standard Care

Standard ICU care includes routine oral care every 2 h, monitoring of ETT position and cuff pressure, and standardised gauze‐based fixation methods. Ventilator‐associated pneumonia prevention measures are applied according to institutional protocols. Detailed procedures are provided in File S2.

2.5.2. Intervention

The intervention consists of standardising ETT repositioning frequency while maintaining all other aspects of care unchanged. Participants will be allocated to either a 4‐h or 8‐h repositioning group, with fixation sites alternated between right, midline and left lip regions. Identical fixation techniques will be used in both groups. The intervention will continue for up to 14 days or until extubation, tracheostomy, ICU discharge or death.

2.5.2.1. RASS‐Based Communication and Monitoring Algorithm

Sedation level will be assessed using the Richmond Agitation‐Sedation Scale (RASS) during ETT repositioning [36, 37, 38, 39, 40]. Responsive patients (RASS ≥ −2) will be informed and assessed for comfort, whereas repositioning in deeply sedated patients (RASS < −2) will follow standard ICU practice.

2.5.2.2. Standardisation Across Intervention Groups

Intervention standardisation will be ensured through structured staff training, written protocols and ongoing monitoring of adherence by the research team. All routine procedures, including ETT fixation and oral care, will be performed according to existing ICU protocols. The only difference between groups will be the predefined ETT repositioning interval (4‐h vs. 8‐h). This approach aims to ensure consistency in care delivery while minimising potential confounding and maintaining internal validity.

2.6. Outcomes and Measures (Follow‐Up Period)

The primary outcome is the incidence of ETT‐related oral MMPIs during the 14‐day follow‐up period, defined as the first occurrence of a pressure‐related lesion (Stages 1–3) on the oral mucosa attributable to the ETT or its fixation device.

Secondary outcomes include MMPI characteristics (stage, anatomical location and time of occurrence) and lesion progression during follow‐up. Adverse events potentially related to ETT repositioning—such as unplanned extubation, device dislodgement, oral bleeding, secretion accumulation and fixation‐related injury—will be prospectively recorded.

Patient comfort indicators, including pain, agitation and delirium, will be assessed using validated tools (NRS or BPS, RASS and CAM‐ICU) (Table 2). Sedation bolus administration associated with repositioning will also be documented.

TABLE 2.

Outcome measurement and assessment protocol.

Outcome/indicator	Assessment tool/data source	Frequency/timing	Person entering data
Oral MMPIs (primary outcome)	Standardised oral inspection/ROMPIS‐TR/OAG	Every 12 h and at clinical change; ROMPIS‐TR assessment once daily	Bedside ICU nurse (event)/principal investigator (verification)
Pain/discomfort	Numeric Rating Scale (NRS) or Behavioural Pain Scale (BPS)	Every 4–8 h per unit routine and as needed	Bedside ICU nurse (event)/principal investigator (verification)
Agitation/sedation level	RASS	Every 4–8 h per unit routine and as needed	Bedside ICU nurse (event)/principal investigator (verification)
Delirium	CAM‐ICU	Once per shift (e.g., twice daily) per unit routine	Bedside ICU nurse (event)/principal investigator (verification)
Adverse events related to repositioning (e.g., unplanned extubation, device dislodgement, oral bleeding, secretion accumulation, fixation‐related skin injury)	Prospective event log + clinical chart review	Continuously monitored or recorded at the time of occurrence	Bedside ICU nurse (event)/principal investigator (verification)
Sedation bolus during/immediately after repositioning	Medication administration record	Each occurrence (during or immediately after repositioning)	Bedside ICU nurse (event)/principal investigator (verification)

Abbreviations: BPS, behavioural pain scale; CAM‐ICU, confusion assessment method for the ICU; ICU, intensive care unit; MMPIs, mucosal membrane pressure injuries; NRS, numeric rating scale; RASS, Richmond agitation‐sedation scale; ROMPIS‐TR, Reaper Oral Mucosa Pressure Injury Scale—Turkish version.

All assessments will be performed daily by trained ICU nurses using the ROMPIS‐TR. MMPI staging and assessment criteria are presented in Table 3.

TABLE 3.

Reaper Oral Mucosa Pressure Injury Scale‐TR.

Stage	Description
Stage 1	Redness and demarcation of the lip and buccal mucosa, with no visible destruction or loss of epithelial tissue, ulceration or blisters. Non‐blanchable erythema on the corners of the mouth.
Stage 2	Destruction and differentiation of buccal mucosa, as manifested by blisters, soft coagulum or clotting on mucosal tissue; superficial loss of non‐keratinised epithelial tissue; or damage to the epidermal and dermal layers of the mouth, without evidence of damage to the underlying fascia
Stage 3	Loss of mucosal and sub‐mucosal tissue as evidenced by damage to/exposure of fascia and underlying muscle in the lips or corners of the mouth.

2.6.1. Follow‐Up Rationale and Duration

The follow‐up period is defined as up to 14 consecutive days of mechanical ventilation, or until extubation, tracheostomy, ICU discharge or death, whichever occurs first. This duration reflects commonly accepted thresholds for prolonged mechanical ventilation and tracheostomy decision‐making [41, 42, 43, 44, 45].

Oral MMPI assessments will be performed daily throughout follow‐up. The first occurrence of MMPI will be used for time‐to‐event analysis; however, follow‐up will continue to capture additional lesions and progression in severity. This approach enables comprehensive evaluation of both MMPI incidence and overall lesion burden.

2.6.2. ROMPIS‐TR Validity, Reliability and Administration

The Reaper Oral Mucosal Pressure Injury Scale (ROMPIS) was developed to assess device‐related oral MMPIs [46]. The Turkish version (ROMPIS‐TR) has been psychometrically validated in ICU settings, demonstrating high internal consistency and strong content validity (Table 4). In the present study, ROMPIS‐TR assessments will be conducted daily by trained ICU nurses following standardised procedures to ensure consistent and reliable outcome measurement.

TABLE 4.

Content validity indices and chance‐corrected agreement (Modified Kappa) for ROMPIS‐TR (Davis technique, n = 7 experts).

Item (stage)	E1	E2	E3	E4	E5	E6	E7	Agreements (3–4)	I‐CVI	P c	κ*	Interpretation
Stage 1	4	4	3	3	4	3	4	7	1.00	0.008	1.00	Excellent
Stage 2	2	4	3	3	3	4	3	6	0.86	0.055	0.85	Excellent
Stage 3	2	4	4	3	3	4	3	6	0.86	0.055	0.85	Excellent
S‐CVI/Ave									0.91			Excellent

Note: I‐CVI: Item‐level Content Validity Index; P _c , probability of chance agreement, calculated as [N!/(A!(N − A)!)] × 0.5 ^N (where N = 7 number of experts, A: number of agreements); κ*: Modified Kappa coefficient, calculated as (I − CVI − P _c )/(1 − P _c ); Interpretation criteria for κ*: > 0.74 = Excellent; 0.60–0.74 = Good; 0.40–0.59 = Fair.

2.6.3. Baseline Variables and Risk Factors

Baseline demographic and clinical variables will be collected to characterise the study population and explore factors associated with oral MMPIs development. A predefined set of intrinsic and extrinsic risk factors, identified from the literature, will be recorded (Table 5). Data will be obtained using a structured form based on ICU records and current evidence.

TABLE 5.

Intrinsic and extrinsic risk factors examined for oral mucosal membrane pressure injury development.

Intrinsic risk factors	Values
Age	Years
Gender	Male/female
Smoking history	Non‐smokers/smoking cigarette
Body mass index (BMI)	kg/m2
Chronic disease status and type	Present/absent
Intensive care unit admission diagnosis	Diagnosis
Vasopressor support, steroid support, antibiotic drugs support and type	Present/absent
APACHE II/SOFA/RASS score	Score (numeric)
Nutrition status
Nasogastric tube/intravenous	NG/IV
Enteral nutrition/parenteral nutrition	EN/PN
Laboratory results
Total protein	g/dL
Albumin	g/dL
CRP	mg/L
WBC	mcL
pH‐pO2‐pCO2	%
Haemoglobin	gr/dL
Blood glucose level	mg/dL
Extrinsic risk factors
ETT repositioning time (4–8 h)	Hours
ETT fixation method	Ribbon gauze (traditional method)
Oral care frequency	Hours
ETT number, depth, location	Number/deep/right–left‐middle
MV mode and values	SIMV‐CPAP/FiO2‐peep‐PSV pressure

Note: Primary outcome: Oral‐MMPI (Absent/Present): The nurse's responsibility is oral mucosa assessment. The oral mucosal PI assessment was limited to the knowledge of the nurse. The nurses who evaluated redness and graze, cyanosis and dehiscence were not observed here (ROMPIS‐TR). ROMPIS‐TR was used to assess the oral mucosa.

Abbreviations: APACHE II, acute Physiology and Chronic Health Evaluation II; BMI, body mass index; CPAP, continuous positive airway pressure; CRP, C‐reactive protein; EN, enteral nutrition; ETT, endotracheal tube; FiO₂, fraction of inspired oxygen; Hb, haemoglobin; ICU, intensive care unit; MMPI, Mucosal membrane pressure injury; MV, mechanical ventilation; NG, nasogastric; pCO₂, partial pressure of carbon dioxide; PEEP, positive end‐expiratory pressure; pH, potential of hydrogen; pO₂, partial pressure of oxygen; PSV, pressure support ventilation; RASS, Richmond Agitation‐Sedation Scale; ROMPIS‐TR, Reaper Oral Mucosa Pressure Injury Scale—Turkish version; SIMV, synchronised intermittent mandatory ventilation; SOFA, Sequential Organ Failure Assessment; WBC, white blood cell count.

2.6.4. Oral Assessment Protocol (Secondary Measure and Secondary Outcomes)

Oral cavity condition will be assessed using an adapted version of the Eilers Oral Assessment Guide (OAG) for intubated patients [47] (Figure 1). In this version, the ‘voice’ and ‘swallowing’ domains are excluded, and the remaining six domains are scored on a three‐point scale, with lower scores indicating better oral health [48].

FIGURE 1.

Eilers' Oral Assessment Guide (OAG) [47].

OAG assessments will be performed daily by trained ICU nurses concurrently with ROMPIS‐TR evaluations to provide complementary information on overall oral health status. The OAG has demonstrated strong validity and reliability in previous studies, including Turkish clinical populations [49].

Outcome assessments will be conducted at a standardised time each day. To enhance reliability, an independent verification process will be implemented, with the principal investigator performing regular cross‐checks and resolving discrepancies using predefined criteria.

2.6.5. Secondary Outcomes

Secondary outcomes will include:

1. Time to first MMPI development during the follow‐up period.

2. Maximum MMPI severity, classified according to ROMPIS‐TR staging.

3. Anatomical distribution of MMPI lesions associated with ETT placement.

2.6.6. Safety Considerations and Potential Complications

Unplanned extubation is the most critical potential complication associated with ETT repositioning. To minimise this risk, repositioning will be performed using standardised procedures, with patient cooperation obtained when feasible. Cuff pressure and tube position will be carefully monitored during each procedure.

ETT securement will be performed using a standardised manual gauze‐based fixation technique, which may reduce mucosal irritation compared with adhesive devices (Figure 2).

FIGURE 2.

Standardised ETT fixation method using manual ribbon gauze and mucosal protective swabs.

Patient tolerance will be assessed during repositioning, and adjustments will be made if discomfort occurs. Potential adverse events, including oxygen desaturation or tube displacement, will be monitored throughout the study.

The intervention does not involve additional pharmacological or invasive procedures; however, relevant clinical parameters and patient comfort indicators will be recorded.

2.6.7. Intervention Adherence and Protocol Deviations

To account for real‐world clinical variability, a maximum flexibility of ±15 min will be allowed for repositioning intervals.

Situations preventing intervention delivery (e.g., emergency procedures and imaging delays) will be documented in detail. Missed or delayed repositioning events will be recorded and incorporated into statistical analyses as adherence‐related variables.

2.6.8. Outcome Recording and Follow‐Up Continuation

The occurrence of the first oral MMPIs will be defined as the primary outcome for time‐to‐event analysis. However, follow‐up will continue after the first MMPI event. Additional lesions occurring in different anatomical regions, as well as progression in lesion severity, will be systematically recorded until the end of the follow‐up period. This approach enables a comprehensive assessment of both MMPI incidence and total lesion burden.

2.6.9. Lesion Management

Upon detection of an MMPI, standard ICU wound care protocols will be initiated. Appropriate local treatments will be applied based on lesion stage. To relieve pressure on affected tissues, the ETT position and repositioning strategy may be adjusted according to clinical need.

2.6.10. Study Flow

The overall study process, including eligibility, randomisation, follow‐up and outcome assessment, is summarised in Figure 3.

FIGURE 3.

Research process Flowchart.

2.7. Sample Size Calculation

Sample size was calculated using G*Power (version 3.1.9.7) based on the primary outcome of MMPI incidence. Assuming a difference between groups (41.5% vs. 26.0%), with α = 0.05 and 80% power, 115 patients per group were required (n = 230). Allowing for 10% attrition, the final sample size was set at 254 participants. Details of the power analysis are presented in Figure 4.

FIGURE 4.

Power analysis graph.

2.8. Randomisation

Participants will be randomly assigned (1:1) to 4‐h or 8‐h ETT repositioning using a computer‐generated sequence. The allocation sequence will be generated prior to recruitment. Stratified block randomisation will be applied based on APACHE II score (≤ 20 vs. 21–24) using Random Allocation Software (version 2.0). Allocation concealment will be ensured using sequentially numbered, opaque, sealed envelopes (SNOSE), prepared centrally. Group allocation will be implemented by an independent staff member not involved in patient care or outcome assessment. Outcome assessors and data analysts will remain blinded to group allocation.

2.9. Blinding and Bias Prevention

2.9.1. Impossibility of Caregiver Blinding

Due to the nature of the intervention, blinding of bedside nurses is not feasible. To minimise performance bias, standardised training will be provided, and adherence to the protocol will be monitored.

2.9.2. Blinded Outcome Assessment and Analysis

This study follows a Prospective Randomised Open, Blinded Endpoint (PROBE) design. Outcome assessors and data analysts will remain blinded to group allocation, and analyses will be conducted using anonymised data.

2.9.3. Objective Outcome Measures

The primary outcome will be assessed using the validated ROMPIS‐TR scale based on predefined clinical criteria. Standardised clinical documentation will support objective evaluation.

2.9.4. Standardised Documentation and Data Quality Assurance

Clinical data will be recorded using standardised case report forms and periodically verified to ensure completeness, consistency and accuracy.

2.10. Statistical Analysis

All analyses will be performed using IBM SPSS Statistics (version 30.0). Data will be checked for completeness and consistency prior to analysis.

2.10.1. Analysis Population and Missing Data

Analyses will follow the intention‐to‐treat principle. A per‐protocol analysis will be conducted as a sensitivity analysis. Missing data will be assessed, and appropriate methods (e.g., complete‐case or multiple imputation) will be applied as needed.

2.10.2. Descriptive Statistics

Baseline characteristics will be summarised using appropriate descriptive statistics. Continuous variables will be reported as mean ± standard deviation or median (interquartile range), and categorical variables as frequencies and percentages.

2.10.3. Primary Outcome Analysis

MMPI incidence will be compared between groups using the chi‐square test. Effect estimates (relative risk, absolute risk difference and 95% confidence intervals) will be reported. Multivariable logistic regression will be used to adjust for repositioning interval and APACHE II category.

2.10.4. Secondary Outcome Analysis

Time‐to‐event analysis will be conducted using Kaplan–Meier methods and compared using the log‐rank test. Other outcomes will be analysed descriptively.

2.10.5. Statistical Significance

A two‐sided p value < 0.05 will be considered statistically significant.

2.11. Ethics Statement

The study protocol was approved by the Hacettepe University Clinical Research Ethics Committee (approval no. 2012‐KAEK‐15/2452), and institutional permission was obtained prior to initiation. The trial was prospectively registered at ClinicalTrials.gov (ID: NCT07390162). The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

Written informed consent will be obtained from legal representatives prior to enrolment. If participants regain decision‐making capacity, consent will be reconfirmed directly.

All data will be anonymised and stored in secure, password‐protected systems accessible only to the research team. Participation will not affect standard clinical care, and participants or their representatives may withdraw at any time without consequences.

3. Discussion

To the best of our knowledge, this protocol represents one of the first randomised controlled trials to directly compare 4‐h and 8‐h ETT repositioning intervals for the prevention of oral MMPIs in adult ICU patients. Although the burden of these injuries is well recognised, current evidence remains insufficient to establish standardised repositioning intervals in clinical practice [5, 27]. This study aims to address this gap by generating high‐quality evidence within a clinically feasible framework.

Previous research has demonstrated that higher APACHE II and SOFA scores are associated with increased risk of oral MMPIs development [12, 22, 24]. However, no randomised study has examined whether repositioning frequency should be adapted according to disease severity. By stratifying patients based on APACHE II scores (≤ 20 vs. 21–24), this study will explore whether the effectiveness of repositioning varies across levels of physiological vulnerability, supporting a more individualised approach to ETT management.

In many ICUs, repositioning practices are guided by local routines rather than evidence‐based recommendations [27]. By comparing 4‐h and 8‐h intervals aligned with both clinical recommendations and routine nursing workflows, this study evaluates not only effectiveness but also feasibility [30]. If less frequent repositioning proves non‐inferior, it may reduce nursing workload without compromising patient safety, particularly in high‐acuity or resource‐limited settings.

The methodological rigour of the protocol further strengthens its contribution. The use of validated tools (ROMPIS‐TR and adapted OAG) ensures standardised outcome assessment, while stratified randomisation, allocation concealment and blinded outcome analysis reduce potential bias. In addition, independent verification of MMPI assessments enhances measurement reliability.

The intervention is also aligned with patient‐centred care principles. Sleep disruption is a significant issue in critically ill patients, contributing to impaired recovery and increased delirium risk [50, 51, 52]. In line with the cluster care approach [53], ETT repositioning is synchronised with routine care (e.g., suctioning and oral care) to minimise additional sleep interruption. While local practices such as frequent oral care and less frequent cuff pressure monitoring reflect current standards, optimisation may be required in light of emerging evidence [30, 54, 21].

From an ethical perspective, the study balances potential benefits and risks. Identifying an optimal repositioning interval may reduce mucosal injury, while risks such as unplanned extubation will be mitigated through standardised procedures and monitoring.

Overall, this trial is expected to provide clinically relevant evidence to guide ETT repositioning practices and support the development of standardised, evidence‐based and severity‐informed airway management strategies in ICU settings.

3.1. Strengths and Limitations

This study has several strengths that enhance its clinical relevance and scientific rigour. Its prospective, randomised controlled design provides high‐level evidence in an area where standardised protocols are lacking. A key strength is the use of stratified randomisation based on disease severity (APACHE II), enabling evaluation of whether repositioning effectiveness varies according to physiological vulnerability. The study also focuses on a common but under‐researched nursing intervention with direct implications for patient safety. Standardisation of the ETT fixation method and the use of validated assessment tools (ROMPIS‐TR), together with independent verification, further strengthen measurement reliability and internal validity.

Several limitations should be considered. The single‐setting design may limit generalisability to ICUs with different organisational structures or patient populations. ETT cuff pressure is assessed using manual palpation rather than manometry, which may introduce measurement variability. Although the follow‐up period is set at 14 days, late‐onset MMPIs may not be fully captured. In addition, adherence to repositioning intervals may be affected by the high‐acuity ICU environment. Finally, exclusion of patients with very high disease severity (APACHE II > 24) may limit applicability to the most critically ill populations.

3.2. Implications and Recommendations for Practice

This study may provide evidence to guide optimal ETT repositioning intervals and support standardisation of ICU nursing practices. Stratified analyses based on APACHE II scores may inform more individualised, risk‐based approaches to airway management. If less frequent repositioning is shown to be effective, this may improve workflow efficiency without compromising patient safety. The findings may also inform future multicentre studies and guideline development.

3.3. Expected Results

This study is expected to determine whether 4‐h ETT repositioning reduces the incidence of oral MMPIs compared with 8‐h repositioning. It is hypothesised that more frequent repositioning will better preserve mucosal integrity and reduce pressure‐related complications. In addition, exploratory analyses may identify clinical and patient‐related factors associated with MMPI development. The findings are expected to inform evidence‐based, standardised approaches to ETT management in ICU settings.

Author Contributions

Study conception and design: E.O., F.K., N.D. Methods prepared: E.O., F.K., N.D. Drafting of the article: E.O., F.K. Critical revision of the article: E.O., F.K.

Funding

The authors have nothing to report.

Ethics Statement

The Clinical Research Ethics Committee of Hacettepe University approved the study on 15.04.2025 (No. 2012‐KAEK‐15/2452). The Clinical Trial Registration number (Unique Protocol ID) is NCT07390162.

Consent

The relatives of the patients were informed about the study, and written informed consent was obtained for each patient.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

File S1: CONSORT 2025 checklist: Updated guideline for reporting randomised trials, providing details on the methodological standards followed in this protocol.

File S2: Routine nursing care clinical practices and ETT management: Detailed procedures regarding the standardised ICU oral care and endotracheal tube management protocols applied in the study units.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.