NCT07434427

Comparison of the Efficacy and Safety of Intravenous Buprenorphine Administered Via PCA System Versus Oxycodone in the Management of Postoperative Pain After Video-Assisted Thoracoscopic Surgery

Comparison of the Efficacy and Safety of Intravenous Buprenorphine Administered Via PCA System Versus Oxycodone in the Management of Postoperative Pain After Video-Assisted Thoracoscopic Surgery - A Prospective, Randomized Clinical Trial

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 200 (estimated)
• Sponsor: Medical University of Silesia · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn whether intravenous buprenorphine administered via a patient-controlled analgesia (PCA) system provides effective and safer postoperative pain control than intravenous oxycodone PCA in adults undergoing video-assisted thoracoscopic surgery (VATS). It will also evaluate the overall tolerability of buprenorphine in the early postoperative period and explore longer-term pain outcomes. The main questions it aims to answer are: Does buprenorphine PCA provide pain control that meets predefined targets during the first 48 hours after VATS (both at rest and during respiratory rehabilitation/mobilization), compared with oxycodone PCA? Does buprenorphine PCA reduce clinically relevant respiratory safety events (e.g., apnea or oxygen desaturation requiring intervention) and excessive sedation, compared with oxycodone PCA? What opioid-related adverse effects (e.g., nausea/vomiting, pruritus, constipation, hypotension) occur with buprenorphine PCA versus oxycodone PCA? Does buprenorphine PCA affect time to first patient-initiated analgesic demand and total opioid consumption within 48 hours? Does the choice of PCA opioid influence quality of recovery and the incidence of persistent postoperative pain at follow-up? Researchers will compare buprenorphine PCA to oxycodone PCA (both as part of standardized multimodal analgesia and perioperative care, including serratus anterior plane block) to determine whether buprenorphine provides non-inferior analgesia with a superior safety profile. Participants will: Be randomly assigned (double-blind) to receive buprenorphine PCA or oxycodone PCA for 48 hours after surgery, alongside standard multimodal analgesia Receive standardized general anesthesia for VATS with one-lung ventilation and an ultrasound-guided serratus anterior plane block at the end of surgery Have pain scores (NRS) recorded at multiple time points over 48 hours, at rest and during rehabilitation, and complete recovery questionnaires (QoR-15) early after surgery Be monitored regularly for vital signs, sedation level (RASS), respiratory events, and other adverse effects, with total opioid use recorded Provide satisfaction ratings at discharge and be followed after discharge to assess persistent postoperative pain/hyperalgesia at 1, 3, and 6 months

Detailed description

This prospective, randomized, double-blind clinical trial is designed to compare the efficacy and safety of intravenous buprenorphine delivered via a patient-controlled analgesia (PCA) system versus intravenous oxycodone PCA for the management of postoperative pain after video-assisted thoracoscopic surgery (VATS). The study will be conducted at the Department of Anesthesiology and Intensive Care, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, and will enroll 200 adult patients aged 18-75 years who are scheduled for elective VATS, have an ASA physical status of I-III, are expected to use a PCA device postoperatively, and provide written informed consent. Prior to randomization, baseline assessment will include age, sex, height, body mass index (BMI), noninvasive arterial blood pressure (systolic, diastolic, and mean), relevant comorbidities (including arterial hypertension, diabetes mellitus, ischemic heart disease, and chronic pain), current analgesic medications, use of psychoactive substances, preoperative pain intensity measured with the Numerical Rating Scale (NRS; 0-10), ASA classification, and confirmation of the patient's ability to appropriately use the PCA pump after surgery. Pain will be evaluated using NRS (0 = no pain; 10 = worst imaginable pain). After eligibility confirmation, patients will be randomized (computerized REDCap system) to one of two treatment arms-OXY or BUPRE-under a double-blind design in which both the patient and the assessor recording pain outcomes remain unaware of the allocated opioid. All participants will receive standardized perioperative analgesia and anesthetic care. As preemptive analgesia administered 30 minutes before incision, patients will receive paracetamol 1.0 g intravenously (Paracetamol Biofarm, Poland) and metamizole 1.0 g intravenously (Pyralgia, Polpharma, Poland). General anesthesia will be performed with double-lumen endotracheal intubation and controlled one-lung ventilation (OLV) tailored to the requirements of VATS. If premedication is required, midazolam 1-2 mg IV will be administered approximately 10 minutes before induction. Standard monitoring will include 3-5 lead ECG, noninvasive blood pressure measurement every 5 minutes, pulse oximetry (SpO₂), capnography (EtCO₂), depth of anesthesia monitoring (BIS), and neuromuscular transmission monitoring (Train-of-Four, TOF). Invasive arterial blood pressure monitoring (arterial line) will be used in prolonged procedures or in patients with increased hemodynamic risk, and arterial blood gas analysis (ABG) will be performed after initiation of OLV and whenever clinically indicated by intraoperative changes. Induction of anesthesia will be achieved with propofol 1.5-2.5 mg/kg IV, fentanyl 1-2 µg/kg IV, and rocuronium 0.6 mg/kg IV to facilitate tracheal intubation. Following loss of consciousness and adequate neuromuscular blockade, a double-lumen tube will be placed, and correct positioning will be confirmed after lateral decubitus positioning and after initiation of OLV. Maintenance anesthesia will use sevoflurane 0.8-1.2 MAC in an air/oxygen mixture with FiO₂ 0.8-1.0, with continued neuromuscular blockade using rocuronium 0.15 mg/kg administered every 20-45 minutes as required. Intraoperative fluid therapy will consist of balanced crystalloid solutions (e.g., Plasmalyte or Optilyte) at 1-4 ml/kg/h according to a goal-directed fluid therapy protocol. Hemodynamic management will include treatment of hypotension with ephedrine 5-10 mg IV or a norepinephrine infusion titrated to maintain mean arterial pressure (MAP) above 70 mmHg. Mechanical ventilation will be delivered in PCV-VG mode. During two-lung ventilation, tidal volume will be set at 6-8 ml/kg predicted body weight (PBW) with PEEP of 5 cmH₂O. During OLV, tidal volume will be reduced to 4-6 ml/kg PBW with PEEP 5-8 cmH₂O and FiO₂ 1.0, and the respiratory rate will be adjusted to maintain EtCO₂ between 35 and 45 mmHg. If hypoxemia occurs, predefined interventions will include alveolar recruitment maneuvers, application of CPAP to the nonoperative lung, or intermittent periods of two-lung ventilation. To provide regional chest wall analgesia, an ultrasound-guided serratus anterior plane block will be performed on the operative side at the end of surgery, prior to transfer to the post-anesthesia care unit (PACU). Using a high-frequency linear probe (6-13 MHz) and a 50-100 mm block needle, the anesthesiologist will identify the latissimus dorsi muscle, serratus anterior muscle, and ribs at the level of the 4th-6th intercostal space in the mid-axillary or posterior axillary line. After skin disinfection and negative aspiration, a small test injection (1-2 ml) will be used to confirm correct fascial plane separation, followed by injection of 20-30 ml of local anesthetic-either 0.25% bupivacaine or 0.375% ropivacaine-selected according to body weight. Depending on patient anatomy and clinician preference, the injection may be performed in the superficial plane (between latissimus dorsi and serratus anterior) or the deep plane (between serratus anterior and the ribs), aiming to cover dermatomes Th2-Th9 of the lateral and anterior chest wall. After surgery, patients will be transferred to the PACU under full vital sign monitoring. Neuromuscular blockade will be reversed with either sugammadex 2 mg/kg or neostigmine 0.04 mg/kg combined with atropine 0.02 mg/kg. Extubation will be performed once predefined criteria are met, including appropriate conscious response and effective spontaneous ventilation, with EtCO₂ below 45 mmHg and SpO₂ above 95%. In the PACU, multimodal analgesia will be continued with paracetamol 1 g IV every 6 hours, metamizole 2.5 g IV every 12 hours, and dexketoprofen 50 mg IV every 8 hours. The PCA pump containing the assigned study opioid will be initiated according to randomization, and prior to leaving the PACU, each patient will receive written information and verbal reinforcement regarding correct PCA use. Transfer to the thoracic surgery ward will occur after achieving at least 9 points on the Aldrete score in two consecutive assessments. The standardized postoperative analgesic regimen will continue on the ward, maintaining multimodal therapy with paracetamol 1 g IV every 6 hours, metamizole 2.5 g IV every 12 hours, dexketoprofen 50 mg IV every 8 hours (if not contraindicated), and PCA with the allocated opioid for a total duration of 48 hours. All patients will have been trained preoperatively on PCA device operation, and they will be monitored for clinical response and adverse events during the PCA period; after 48 hours, the PCA will be discontinued and analgesia will proceed according to standard multimodal protocols. The investigational opioid regimens are standardized in both groups. In the buprenorphine arm (Group BUPRE), intravenous buprenorphine will be prepared as 1 mg in 50 ml of 0.9% sodium chloride, with a PCA bolus dose of 0.02 mg (1 ml), a lockout interval of 15 minutes, a maximum hourly dose of 0.08 mg, and a maximum potential daily dose of 1.92 mg. In the oxycodone arm (Group OXY), intravenous oxycodone will be prepared as 40 mg in 40 ml of 0.9% sodium chloride, with a PCA bolus dose of 1 mg (1 ml), a lockout interval of 15 minutes, a maximum hourly dose of 4 mg, and a maximum daily dose of 96 mg. During the immediate postoperative period and throughout the first 48 hours, predefined monitoring and outcome collection will be performed. Heart rate will be recorded every 4 hours, and noninvasive arterial blood pressure (SBP, DBP, MAP) will be measured every 4 hours. Pain intensity will be assessed using NRS at 2, 6, 12, 24, and 48 hours after surgery, both at rest and during respiratory rehabilitation procedures and mobilization. Quality of recovery will be evaluated using QoR-15 on postoperative days 1 and 3. Time to first patient-initiated analgesic intervention will be recorded as the interval from completion of anesthesia and discontinuation of anesthesiologist-administered opioids at NRS ≤2 to the first PCA bolus request. Total opioid consumption over 48 hours will be documented and expressed in milligrams and morphine milligram equivalents (MME). Safety and tolerability outcomes will be captured systematically. Excessive sedation/drowsiness will be assessed using the Richmond Agitation-Sedation Scale (RASS), with RASS ≤ -1 considered excessive sedation. Constipation, postoperative nausea and vomiting (PONV), and pruritus will be documented. Respiratory disturbances will be assessed every 4 hours, with apnea defined as at least a 90% reduction in respiratory amplitude lasting at least 10 seconds and/or any episode of cyanosis; clinically significant respiratory depression will be defined as apnea episodes, respiratory rate below 8 breaths per minute, or SpO₂ below 92% requiring intervention. Hypotension will be recorded when MAP falls below 70 mmHg. At hospital discharge, overall satisfaction with analgesic treatment will be assessed using a Likert scale, and length of hospital stay will be recorded. Longer-term follow-up will evaluate persistent postoperative pain and/or hyperalgesia at 1, 3, and 6 months after surgery using NRS and structured pain questionnaires, to explore potential differences in chronic postsurgical pain outcomes between the two opioid strategies. The primary endpoint is the comparative assessment of efficacy and safety of buprenorphine PCA versus oxycodone PCA within the first 48 postoperative hours in the context of multimodal analgesia after VATS, operationalized as achieving effective pain control (mean NRS ≤3 at rest and ≤4 during rehabilitation and mobilization), maintaining adequate respiratory safety (no clinically significant respiratory depression requiring intervention), and demonstrating a reduced incidence of opioid-related adverse effects. Secondary endpoints include time to first PCA bolus, cumulative opioid consumption (including MME), NRS profiles across repeated time points, QoR-15 scores on postoperative days 1 and 3, incidence of opioid-related adverse events (PONV, pruritus, constipation, excessive sedation, respiratory depression/apnea, hypotension), frequency of excessive sedation events defined by RASS ≤ -1, length of hospitalization, patient satisfaction with analgesia, and the prevalence and intensity of chronic postsurgical pain at follow-up. Statistical analysis will follow the intention-to-treat principle. Quantitative variables will be analyzed using Student's t-test or the Mann-Whitney U test depending on distribution, categorical variables using chi-square or Fisher's exact test, and repeated NRS measurements using repeated-measures ANOVA. Statistical significance will be set at p \< 0.05. The projected study period extends from anticipated bioethics approval on January 15, 2026, through completion of recruitment and data analysis by December 31, 2027.

Conditions

• Acute Postoperative Pain
• Chronic Postoperative Pain
• Toracosurgery
• Video-assisted Thoracis Surgery (VATS)

Interventions

Type	Name	Description
DRUG	Group B (Buprenorphine)	Intravenous buprenorphine administered via PCA pump (1 mg / 50 ml 0.9% NaCl): bolus dose: 0.02 mg (1 ml solution), lockout interval: 15 minutes, maximum hourly dose: 0.08 mg, maximum potential daily dose: 1.92 mg.
DRUG	Group O (Oxycodone)	Intravenous oxycodone administered via PCA pump (40 mg / 40 ml 0.9% NaCl): bolus dose: 1 mg (1 ml solution), lockout interval: 15 minutes, maximum hourly dose: 4 mg, maximum daily dose: 96 mg.

Timeline

• Start date: 2026-02-01
• Primary completion: 2027-05-01
• Completion: 2027-11-01
• First posted: 2026-02-25
• Last updated: 2026-02-25