Comparison of oxycodone hydrochloride injection versus sufentanil for postoperative analgesia in patients undergoing minimally invasive cardiac valve replacement: study protocol for a single-centre, randomised, double-blind non-inferiority trial

Abstract

Introduction

With the advancement of the ERAS (Enhanced Recovery After Surgery) concept, minimally invasive heart valve replacement surgery has become widely performed due to its advantages of smaller trauma and fewer adverse reactions. However, postoperative pain management remains complex and traditional opioid analgesia is often associated with adverse side effects. Oxycodone, an opioid agonist, has strong analgesic effects with relatively few side effects. This study aims to explore the efficacy and safety of oxycodone hydrochloride injection in multimodal pain management following minimally invasive heart valve replacement surgery.

Methods and analysis

This is a prospective, double-blind, randomised controlled clinical trial designed as a non-inferiority study. The schedule of enrolment, interventions and outcome assessments is summarised in figure 2. The study period is from October 2024 to September 2027, and between 30 April 2026 and 31 October 2026, a total of 130 patients undergoing minimally invasive heart valve replacement surgery will be planned to recruit and randomly assign in a 1:1 ratio to receive either oxycodone hydrochloride injection or sufentanil for postoperative patient-controlled analgesia. The primary outcome is the Numerical Rating Scale pain score during coughing at 24 hours postoperatively. Secondary outcomes include measures of postoperative pain control, analgesic consumption, adverse events and recovery-related indicators. To address the risk of type I error due to multiple secondary outcomes, secondary endpoints are prespecified and categorised into key secondary outcomes and exploratory outcomes with corresponding statistical analysis strategies planned. This protocol is V.2.0, dated 29 December 2025.

Ethics and dissemination

Ethical approval has been obtained from the Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University (XJTU1AF2024LSYY-389-04). The study will be conducted in accordance with the Declaration of Helsinki, and informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed journals, scientific conferences and appropriate public channels.

Trial registration

ChiCTR2400094930.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Blinding of participants and outcome assessors will minimise bias and ensure objective evaluation of postoperative pain.

• The primary outcome focuses on pain during coughing, which is clinically relevant in an Enhanced Recovery After Surgery setting.

• As a single-centre study, the generalisability of the findings may be limited by regional and institutional factors.

• The sample size is powered to assess non-inferiority in analgesic efficacy but is not sufficient to detect differences in rare adverse events.

• Pain intensity is assessed using the Numerical Rating Scale, which is subjective and may be influenced by individual patient perception.

Introduction

Valvular heart disease (VHD) encompasses pathological alterations in heart valves due to various aetiologies, leading to stenosis or regurgitation that disrupts normal cardiac haemodynamics and ultimately results in cardiac dysfunction. As a prevalent cardiovascular disorder, its incidence continues to rise, driven by global population ageing and improved survival rates. In 2021, the global burden of VHD attributed to rheumatic heart disease reached 41 million cases, while degenerative mitral valve disease and calcific aortic stenosis accounted for 24 million and 9 million cases, respectively.¹ Without timely intervention, VHD can lead to severe complications, including malignant arrhythmias, heart failure and sudden cardiac death, significantly impacting patients’ quality of life and survival. Heart valve replacement surgery (HVRS) remains the primary treatment for severe VHD.²

Traditional HVRS requires a median sternotomy with an incision of approximately 20 cm, which is associated with substantial surgical trauma and a high incidence of perioperative complications. Recently, minimally invasive HVRS has emerged as an alternative approach, aligning with the principles of Enhanced Recovery After Surgery (ERAS). This technique integrates evidence-based perioperative optimisation strategies, including preoperative preparation, intraoperative management, postoperative rehabilitation and comprehensive nursing care. By mitigating the surgical stress response, minimally invasive HVRS aims to reduce complications, shorten hospital stays and lower the risk of readmission and mortality, thereby promoting faster recovery.^{3 4} Compared with conventional sternotomy, minimally invasive HVRS employs a 4–5 cm right anterolateral intercostal incision, preserving chest wall integrity and stability. This approach offers several advantages, including reduced surgical trauma, less intraoperative bleeding, diminished postoperative pain, fewer perioperative complications—such as bleeding, acute kidney injury and new-onset atrial fibrillation—and accelerated recovery.⁵,⁸ Notably, approximately 30% of patients with clear surgical indications for HVRS decline surgery due to advanced age and high surgical risk.⁹ Minimally invasive HVRS, with its reduced surgical burden and expedited recovery, presents a viable option for elderly and high-risk patients and is increasingly being adopted as the preferred treatment modality for VHD.

Postoperative pain remains a significant challenge in anaesthesia management following minimally invasive HVRS, as it can exacerbate stress responses and anxiety in patients. If inadequately managed, persistent pain may contribute to complications such as infection and thrombosis, increasing overall perioperative risk. Therefore, effective postoperative analgesia is a crucial component of ERAS protocols.¹⁰,¹³ Multimodal analgesia strategies typically combine intercostal nerve blocks with intravenous patient-controlled analgesia (PCA). Among opioid analgesics, sufentanil is commonly administered via PCA due to its potent analgesic properties mediated through μ-opioid receptor activation. However, its use is associated with respiratory depression and dose-dependent adverse effects such as nausea, vomiting and sedation, which may hinder postoperative recovery.^{14 15} Furthermore, its active metabolite, nor-sufentanil, retains pharmacological activity, increasing the risk of cumulative adverse effects.

Oxycodone is a semisynthetic opioid analgesic that primarily exerts its analgesic effects through activation of the μ-opioid receptor and has been widely used for the management of moderate-to-severe postoperative pain.^{16 17} Following intravenous administration of 10 mg oxycodone, peak plasma concentrations are reached within several minutes, with a terminal half-life of approximately 3.5 hours, which facilitates clinical use and dose titration.^{18 19} In terms of safety, the analgesic effect of oxycodone is mainly mediated by the parent compound, while its active metabolites are present at relatively low plasma concentrations (approximately 2%) and are generally considered to contribute minimally to its overall analgesic effect.²⁰ Oxycodone possesses moderate lipophilicity, which may reduce drug accumulation and potentially lower the risk of opioid-related adverse effects. Compared with some potent opioids, oxycodone has a relatively lower affinity for the μ-opioid receptor, which may be associated with a more favourable respiratory safety profile. Importantly, opioid-related adverse effects can be effectively reversed with naloxone when necessary.²¹ In addition, studies in thoracic, abdominal, orthopaedic and gynaecological surgery have suggested that, compared with potent opioids such as sufentanil and fentanyl, oxycodone may be associated with a lower incidence of certain opioid-related adverse effects, including nausea, vomiting, pruritus, dizziness and headache.²²,²⁴ Furthermore, the use of oxycodone for preventive analgesia has shown potential advantages in suppressing postoperative cough, visceral pain and inflammatory responses, and may be superior to sufentanil in certain surgical settings. Previous studies have also indicated that oxycodone may attenuate perioperative oxidative stress and inflammatory cascades, which could be associated with enhanced postoperative recovery.^{25 26} However, the analgesic efficacy and safety of oxycodone in minimally invasive HVRS have not been fully investigated. Therefore, the present study aimed to evaluate the efficacy and safety of intravenous oxycodone for postoperative analgesia in patients undergoing minimally invasive HVRS.

Patient and public involvement

Patients or members of the public were not involved in the design, conduct, reporting or dissemination plans of this research. The research questions, study outcomes and methodology were determined by the investigators based on current clinical practice needs and evidence gaps. The study protocol, consent forms and patient information sheets were reviewed and approved by the institutional ethics committee prior to implementation. The results will be disseminated to participants and the public through academic publications and presentations.

Methods and analysis

Study design and setting

This prospective, double-blind, randomised controlled trial will be conducted in the cardiac surgery intensive care unit (CCU) at the First Affiliated Hospital of Xi'an Jiaotong University. All personnel involved in the study are certified professionals accredited by the hospital. The protocol is reported in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Study flow see figure 1. The overallstudy design, interventions, and assessment schedule are shown in figure 2.

Figure 1. Study flow diagram illustrating participant screening, enrolment, randomisation, intervention allocation, follow-up and analysis. PCA, patient-controlled analgesia.

Figure 2. Participant timeline showing enrolment, randomisation, interventions and outcome assessments throughout the study period. NRS, Numerical Rating Scale; PCA, patient-controlled analgesia; PONV, postoperative nausea and vomiting; QoR-15, Quality of Recovery-15.

Eligibility criteria

• Inclusion criteria: Patients scheduled to undergo minimally invasive HVRS at the hospital, aged 18–85 years, with a body mass index of 18–30 kg/m² and classified as American society of Anesthesiologists (ASA) physical status, will be eligible. Additionally, participants must demonstrate understanding and willingness to use PCA and provide informed consent. Enrolment will include patients admitted to the CCU between 30 April 2026 and 31 October 2026.

• Exclusion criteria: Patients will be excluded if they present with chronic pain syndrome, a history of severe postoperative nausea and vomiting (PONV) or drug abuse, psychiatric disorders, opioid allergies or prolonged opioid use. Additional exclusion criteria include severe dysfunction of the liver and kidneys (include Child-Turcotte-Pugh >9 and preoperative dialysis required), cognitive impairment affecting PCA use. Patients who withdraw from the study during follow-up will also be excluded.

• Exit criteria:

  1. Patients undergoing unplanned reoperation after minimally invasive heart valve replacement will be excluded from the study.

  2. Patients with endotracheal intubation for more than 24 hours postoperatively will be withdrawn from the study.

Recruitment

Participants will be recruited from admission until the time of surgery, the planned recruitment date is between 30 April 2026 and 31 October 2026. Patients scheduled for minimally invasive HVRS and anticipated to be admitted to the CCU postoperatively will be screened for eligibility. Study personnel will contact potential candidates and their legally authorised representatives (in accordance with the laws of the People’s Republic of China) before surgery for an initial screening assessment. If patients meet all inclusion criteria, the study objectives, benefits and risks will be thoroughly explained. Written informed consent will be obtained from the patient or their legally authorised representative. For critically ill patients unable to provide consent personally, their legally authorised representative will provide consent in compliance with legal requirements.

Randomisation and blinding

Randomisation will be performed prior to surgery once eligibility is confirmed. An independent statistician will generate a computer-based randomisation sequence using a 1:1 allocation ratio to assign participants to either the oxycodone group (A group) or the sufentanil group (B group). Allocation concealment will be ensured using opaque, sealed envelopes prepared according to the randomisation schedule by personnel not involved in participant recruitment, clinical care or outcome assessment. The envelope corresponding to each participant will be opened only after enrolment to determine treatment allocation.

This study is double-blind. Patients, investigators involved in patient care and intervention administration, outcome assessors, data collectors and statistical analysts will all remain blinded to group allocation throughout the study. To maintain blinding, PCA will be delivered using identical pumps prepared in an indistinguishable manner. Routine unblinding will occur only after database lock. Emergency unblinding may be performed if knowledge of the allocated treatment is required for patient safety. Statistical analysts will all remain blinded to treatment allocation throughout the study.

Non-inferiority margin

The non-inferiority margin (δ) was prespecified as a 1-point absolute difference on the 0–10 Numerical Rating Scale (NRS). This margin was primarily informed by the minimal clinically important difference (MCID) for acute postoperative pain. Previous studies have reported that the MCID for acute postoperative pain is approximately 1 point on the visual analogue scale (VAS), representing the smallest change in pain intensity perceived as clinically meaningful by patients and the high correlation between VAS and NRS scores reported in the literature,²⁷ the use of a 1-point difference on the NRS as the non-inferiority margin is considered clinically reasonable. In addition, acute postoperative analgesic interventions typically reduce pain intensity by approximately 3–4 points on the NRS. Therefore, a non-inferiority margin of 1 point represents a conservative and clinically acceptable difference, corresponding to approximately 25–33% of the expected analgesic effect.²⁸ From a methodological perspective, a 1-point NRS non-inferiority margin has also been adopted in previous non-inferiority randomised controlled trials involving postoperative pain management and PCA,²⁹ further supporting the appropriateness of this margin.

Sample size

This study is designed as a non-inferiority trial comparing oxycodone hydrochloride injection with sufentanil for postoperative analgesia in patients undergoing minimally invasive HVRS. The primary outcome is the NRS pain score during coughing at 24 hours postoperatively, analysed as a continuous variable. As no previous studies have reported coughing-related NRS scores in this specific surgical population, the SD required for sample size estimation was informed exclusively by data obtained under sufentanil-based postoperative analgesia. This included an unpublished internal retrospective study (20 patients, all receiving serratus anterior plane block and sufentanil PCA) and published thoracoscopic surgery studies reporting the distribution of postoperative pain scores during activity or coughing. Although some of these studies presented results graphically without providing exact numerical values, the overall range of pain score distributions was comparable to that observed in our retrospective analysis.^{30 31} In addition, retrospective analyses in related surgical settings have explicitly reported SD of postoperative pain scores in the range of approximately 1.6–1.7.³² Assuming a common SD of 1.6, a one-sided significance level of 0.025, and a power of 90%, allowing for an anticipated dropout rate of 15%, the final target sample size was set at 130 participants, with 65 patients in each group.

Intervention

Patients will be randomised on entering the operating room before surgery commencement.

• Anaesthesia management: Anaesthesia protocols will be standardised to minimise variability. Prior to induction, patients will receive penehyclidine hydrochloride (0.5 mg) and dexamethasone (5 mg). Preoperative ultrasound-guided anterior serratus muscle plane block will be performed at the level of the third intercostal space on the anterior axillary line, using ropivacaine with a concentration of 0.5% and a volume of 20 mL. Intravenous anaesthesia induction will include midazolam (0.02 mg/kg), etomidate (0.2–0.3 mg/kg), sufentanil (0.5 µg/kg) and rocuronium (0.6 mg/kg). Anaesthesia maintenance will be achieved with propofol (3–6 mg/kg/hour), remifentanil (0.1–0.3 μg/kg/min), atracurium besylate (0.1 mg/kg/hour) and dexmedetomidine (0.2–0.7 μg/kg/hour), supplemented with sevoflurane (0.5–1%). If the patient’s heart rate suddenly increases and blood pressure rises during the operation, it is considered as insufficient analgesia after excluding the causes of shallow anaesthesia, surgical stimulation, insufficient blood volume, hypoxaemia, carbon dioxide retention, vasoactive drugs, etc, and an additional 0.1 µg/kg of sufentanil is administered. The Bispectral Index will be maintained between 40 and 60, with heart rate and blood pressure fluctuations kept within 25% of baseline values. Ventilator settings will include a tidal volume of 6–8 mL/kg, a respiratory rate of 12–20 breaths/min and an end-tidal CO₂ concentration maintained between 35 and 45 mm Hg. Anticoagulation will be achieved with heparin to maintain an activated clotting time (ACT) above 480 s. All patients require cardiopulmonary bypass (CPB), the same ultrafiltration system (Dideco) will be used. CPB management will involve maintaining a body temperature of 34°C, mean perfusion pressure between 60 and 80 mm Hg and a pump flow rate of 2.0–2.4 L/min/m². Hypothermic circulatory arrest at 20°C will be employed with antegrade cerebral perfusion. Patients will be rewarmed to 36–37°C before CPB separation. Heparin reversal with protamine sulfate (1 mg per 100 units of heparin) will be administered to restore ACT to within 10% of baseline. Ondansetron (4 mg) will be administered 15 min before the end of anaesthesia. Postoperatively, all patients will be transferred to the CCU for standard postoperative care.

• Experimental group: oxycodone hydrochloride injection: Following surgery, the study drug will be administered via a PCA pump, with dosage individualised based on patient weight and physiological parameters, adhering to the protocol’s specified range. 50 mg of oxycodone is added to physiological saline to prepare a total of 100 mL of experimental solution. The parameters set for the PCA pump include the initial loading dose of 1–3 mL (the dosage of oxycodone is 0.5–1.5 mg), PCA dose of 2–4 mL (the dosage of oxycodone is 1–2 mg), the locking time of 10 min and the continuous infusion rate of 1–2 mL/hour (0.5–1 mg/hour). The target pain relief goal is an NRS score between 0 and 3, where 0 represents no pain and 10 represents the worst pain imaginable.

• Control group: sufentanil citrate injection: The control group will receive sufentanil via PCA immediately postoperatively, with doses individualised per-protocol (PP). 100 μg of sufentanil was added to physiological saline to prepare a total of 100 mL of experimental solution. The parameters set for the PCA pump include the initial loading dose of 1–3 mL (the dosage of sufentanil is 1–3 μg), PCA dose of 2–4 mL (the dosage of sufentanil is 2–4 μg), the locking time of 10 min and the continuous infusion rate of 1–2 mL/hour (1–2 μg/hour). The target pain relief goal is an NRS score between 0 and 3.

• Emergency management in the experimental group: If the NRS score remains ≥4 despite reaching the maximum PCA dose (2 mg per dose) and continuous infusion rate (1 mg/hour), intravenous remifentanil (0.03–0.05 μg/kg/min) may be administered for supplemental analgesia. If pain persists, subcutaneous morphine hydrochloride (5 mg) will be given. No additional analgesics will be permitted except for predefined rescue analgesia. For severe PONV, rescue treatment with ondansetron (4 mg) will be provided.

Outcome measures

Primary outcome: The primary outcome is the NRS pain score during coughing at 24 hours postoperatively.

Secondary outcomes: As this study includes a relatively large number of secondary outcomes, several outcomes were prespecified as key secondary outcomes, while the remaining outcomes were designated for exploratory analyses.

The key secondary outcomes include

• The area under the curve (AUC) of NRS scores at rest and during activity between 24 and 48 hours postoperatively.

• NRS scores at 36 and 48 hours postoperatively, assessed at rest and during activity.

• Total consumption of the study drug and rescue analgesics within 48 hours after surgery.

• The incidence of moderate-to-severe pain and the maximum pain intensity within 48 hours postoperatively.

• The total number of PCA button presses and the number of effective presses.

• The incidence of PONV and the dosage of antiemetic drugs.

The exploratory secondary outcomes include

• Quality of Recovery-15 (QoR-15) scores at 24 and 48 hours postoperatively.

• Anaesthesia duration.

• Time to extubation.

• Time to first postoperative flatus and defecation.

• Time to removal of urinary and drainage catheters.

• Total length of hospital stay.

• The incidence of respiratory depression, hypoxaemia, hypotension and allergic reactions within 48 hours postoperatively.

• The dosage of vasoactive drugs administered within 48 hours after surgery.

Data collection and management

Primary outcome

Postoperative pain intensity will be assessed using the 11-point NRS (0=no pain, 10=worst imaginable pain). Pain assessments will be performed by trained study personnel who are blinded to group allocation. Patients will be instructed preoperatively on the use of the NRS. At 24 hours after surgery, patients will be asked to cough, and the corresponding NRS score will be recorded in the electronic case report form (eCRF).

Key secondary outcomes were assessed as follows

• Postoperative pain at predefined time points: Pain intensity at rest and during movement was assessed using the NRS at 24, 36 and 48 hours after surgery. The AUC of NRS scores at rest and during movement between 24 and 48 hours postoperatively was calculated using the trapezoidal method. Patients who experienced an NRS score ≥4 at any time within 48 hours after surgery were classified as having moderate-to-severe pain, and the incidence of moderate-to-severe pain as well as the maximum NRS score during the first 48 postoperative hours were recorded.

• Analgesic consumption: Total consumption of study medication and rescue analgesics within 48 hours after surgery was automatically recorded by the PCA device and verified against medication administration records.

• PCA use patterns: The total number of PCA button presses and the number of effective demands within the first 48 postoperative hours were extracted from the PCA pump records.

• PONV: The number of episodes of nausea and vomiting and the use of antiemetic medications within 48 hours after surgery were documented by nursing staff based on patient reports and medical records.

Exploratory secondary outcomes included

• QoR: Postoperative recovery quality was assessed at 24 and 48 hours after surgery using the validated QoR-15 questionnaire.

• Time-related outcomes: Anaesthesia duration, time to extubation, time to first postoperative flatus and defecation, time to removal of urinary catheter and surgical drains, and total length of hospital stay were obtained from clinical records.

• Safety outcomes: The incidence of respiratory depression, hypoxaemia, hypotension and allergic reactions within 48 hours after surgery, as well as the use of vasoactive medications, were recorded based on clinical monitoring data and adverse event reports.

Plans to promote participant retention and complete follow-up

Postoperative pain is primarily an acute outcome that occurs during the early postoperative period. Therefore, this study focused on pain-related outcomes within the first 48 hours after surgery which minimises the risk of loss to follow-up. All outcome assessments are integrated into routine postoperative clinical care to reduce participant burden. Study personnel will emphasise the importance of completing all scheduled assessments to participants and clinical staff. Data will be collected according to the intention-to-treat (ITT) principle. All randomised participants will be included in the primary analysis according to their allocated group. For participants who discontinue the intervention or deviate from the protocol after randomisation, all available data up to the time of withdrawal or deviation will be retained and included in the analysis, along with documentation of the reasons for discontinuation.

Data management

Before the commencement of the study, an eCRF will be established, which will feature password-protected access to ensure data security. Original data will be archived following the guidelines set out in the good clinical practice for clinical trials. The data lock will be implemented only after all quality assurance processes have been completed, ensuring that the data set is finalised and ready for analysis.

Statistical analysis

Statistical analyses will include descriptive and inferential analyses.

A one-sided test will be applied for the primary non-inferiority analysis, while all other analyses will be conducted using two-sided tests. All analyses will be performed using SAS software (V.9.4). Unless otherwise specified, a two-sided p value <0.05 will be considered statistically significant.

Analysis populations and missing data

• The primary analysis will be conducted in the ITT population, including all randomised participants analysed according to their assigned groups. A PP analysis will be performed as a sensitivity analysis to assess robustness.

• Missing data will be handled using multiple imputation where appropriate. Complete-case analyses may be conducted as supplementary sensitivity analyses if the proportion of missing data is minimal.

Descriptive analysis

Continuous variables will be summarised as mean±SD for normally distributed data, or median (IQR) for non-normally distributed data. Categorical variables will be presented as frequencies and percentages.

Primary outcome analysis (non-inferiority)

• The primary outcome is the NRS pain score during coughing at 24 hours postoperatively, analysed as a continuous variable. The between-group difference will be estimated as Δ=mean(NRS_oxycodone − NRS_sufentanil), along with its 95% CI. Non-inferiority will be concluded if the upper bound of the 95% CI for Δ is less than the predefined non-inferiority margin (δ=1 NRS point). The primary analysis will use an independent samples t-test. If distributional assumptions are violated, appropriate robust methods will be applied.

• As a sensitivity analysis, a linear regression model adjusting for prespecified covariates (age, ASA class and duration of surgery) will be used.

Key secondary outcomes

Predefined key secondary outcomes will be analysed as confirmatory outcomes. Each outcome will be analysed using statistical models appropriate to its data type:

• Continuous outcomes: linear regression or non-parametric tests.

• Binary outcomes: logistic regression.

• Count outcomes: Poisson or negative binomial regression, as appropriate.

To control the family-wise type I error rate across key secondary outcomes, Holm-Bonferroni adjustment will be applied.

Exploratory outcomes

Exploratory outcomes will be analysed descriptively. No adjustment for multiple comparisons will be applied, and results will be interpreted as hypothesis-generating.

Protocol amendments

Following peer review, several modifications were made to the original study protocol prior to initiation of participant recruitment.

The primary outcome was revised from the rate of effective analgesia at rest at 24 hours postoperatively (a dichotomous outcome) to the NRS score during coughing at 24 hours postoperatively. This change was made to improve clinical relevance within an ERAS framework and to avoid loss of information associated with dichotomisation.

As a consequence of this change, the sample size calculation and statistical analysis plan were updated accordingly.

In addition, secondary outcomes were reclassified into key secondary outcomes and exploratory outcomes to better address multiplicity and reduce the risk of type I error. These amendments were implemented prior to recruitment, and no participants were enrolled under the original protocol. The trial registry has been updated to reflect the revised protocol.

Ethics and dissemination

This study has been approved by the Ethics Committee of the First Affiliated Hospital of Xi‘an Jiaotong University (approval number: XJTU1AF2024LSYY-389-04). The study will be conducted in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants prior to enrolment; where participants are unable to provide consent, consent will be obtained from their legally authorised representatives in accordance with Chinese law. The participant informed consent form is provided as online supplemental file 1.

Any important modifications to the study protocol will be submitted to the institutional ethics committee for approval prior to implementation. Approved amendments will be updated in the trial registry and reflected in the protocol manuscript as appropriate. Substantive protocol amendments have been approved by the ethics committee, and the trial registry has been updated accordingly to reflect the revised protocol.

The findings of this trial will be disseminated through peer-reviewed journal publications and presentations at national and international scientific conferences and will be made available to patients and the public through appropriate channels. The study protocol, informed consent materials and key findings will be available from the corresponding author on reasonable request. Following completion of the trial, the dataset and statistical code will be shared on reasonable request.

Patient and data safety monitoring

In addition to routine intensive care monitoring, full-time certified physicians and certified nurses will be responsible for patient observation. The internal medical advisory team of the research team will be available 24 hours a day to provide any drug-related consultations. All serious adverse events and non-serious adverse events (including unexpected events) will be recorded in the study database and reported to the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University as required. Regular audits will be conducted by an independent data monitoring committee on a quarterly basis to ensure the integrity, accuracy and reliability of the data collected.

Harm

Oxycodone hydrochloride injection is an approved drug, and its safety and efficacy have been validated. Adverse events will be monitored during its use. The investigators will record all adverse events, including severe hypotension and respiratory depression. If any of these adverse events occur, the bedside physician can suspend the participant’s involvement in the study and unblind the participant. In such cases, the event that led to the suspension of the study will be recorded and reported to the Institutional Review Board of the First Affiliated Hospital of Xi'an Jiaotong University within 24 hours.

Discussion

Although previous studies have explored postoperative analgesic strategies involving oxycodone and other opioid agents, existing evidence has primarily focused on thoracic and abdominal surgical procedures. Evidence regarding postoperative analgesia in patients undergoing minimally invasive cardiac valve replacement remains limited. Minimally invasive cardiac valve surgery, an increasingly adopted technique, is associated with reduced surgical trauma and faster recovery and is consistent with the principles of ERAS. Effective postoperative pain control is a key component of ERAS pathways, highlighting the need for appropriate analgesic strategies in this patient population. Oxycodone hydrochloride has pharmacological characteristics, including dual µ- and K-opioid receptor agonism and relatively low lipid solubility, which may offer potential advantages for postoperative pain management, particularly for visceral pain. However, high-quality clinical evidence supporting its use in minimally invasive cardiac valve surgery is currently lacking. This trial is therefore designed to systematically evaluate the efficacy and safety of oxycodone hydrochloride injection compared with sufentanil in this specific surgical setting, with the aim of providing methodologically robust data to inform postoperative analgesic strategies. This study has several limitations. First, as a single-centre trial, the generalisability of the findings may be limited, and results may not fully represent outcomes across different institutions or patient populations. Second, postoperative pain will be assessed using the NRS, which relies on patients‘ subjective perceptions and may be influenced by individual variability, potentially introducing measurement bias. Third, the planned sample size is not sufficient to reliably detect rare opioid-related adverse events. Future multicentre studies with larger sample sizes may be required to further evaluate the safety profile and external validity of the findings.