Acetaminophen vs Placebo for Postoperative Analgesia After Abdominal Surgery
Comparison of Placebo and Acetaminophen on Postoperative Opioid Consumption in Non-Cardiac Abdominal Surgery
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Detailed Description:
Postoperative pain remains a major clinical challenge despite advances in analgesic pharmacology and surgical technique, contributing to delayed mobilization, prolonged hospital stay, and increased morbidity. Oral acetaminophen is widely used as part of multimodal analgesia regimens, but high-quality evidence supporting its independent analgesic effect - as distinct from placebo response - remains limited, particularly after major abdominal surgery.
This is a prospective, multicenter, randomized, double-blind, placebo-controlled trial enrolling adults undergoing elective non-cardiac abdominal surgery under general anesthesia, with an expected surgical duration of at least 2 hours and a planned hospital stay of at least 48 hours. Prior to the main trial, each participating site will enroll a minimum of 10 pilot patients to confirm proper implementation of the analgesic protocol.
Eligible patients will be randomized 1:1 using a web-based system (REDCap) with random-sized blocks to receive either oral acetaminophen 1000 mg or matching placebo tablets. The first dose will be administered 30 minutes before surgery, followed by repeat dosing every 6 hours for 48 hours postoperatively. All patients will receive a standardized intraoperative analgesic protocol (fentanyl 1.5 mcg/kg at induction; tramadol 2 mg/kg approximately 30 minutes before anticipated completion of surgery), with postoperative rescue analgesia provided via patient-controlled analgesia (tramadol; demand dose 10 mg, lockout 6 minutes, continuous baseline 10 mg/h) and per-patient-request dosing (tramadol 1 mg/kg for pain score >4).
The joint primary outcomes are (1) total opioid consumption (expressed as IV morphine milligram equivalents) and (2) average postoperative pain score (0-10 visual analog scale), both assessed over the first 48 postoperative hours. Acetaminophen will be considered superior to placebo only if it demonstrates both statistical superiority on opioid consumption and statistical noninferiority on pain score (noninferiority margin of 1 point), tested jointly at an overall one-sided alpha of 0.025. Opioid consumption will be analyzed using a linear regression model on log-transformed values; pain score will be analyzed using a repeated-measures linear regression model with an autoregressive correlation structure.
Secondary outcomes include patient-reported satisfaction with postoperative pain management at 24 and 48 hours. Exploratory outcomes include a composite measure of opioid-related side effects (Opioid-Related Symptom Distress Scale, ORSDS), capturing nausea, vomiting, constipation, sedation, dizziness, and related symptoms.
Based on a sample size calculation incorporating group sequential interim analyses (planned at each 25% of enrollment), a maximum of 1504 patients (752 per group) will be enrolled to achieve approximately 90% overall power at the 0.025 significance level. An internal pilot analysis at 25% enrollment will re-evaluate sample size assumptions based on observed variability in opioid consumption.
Data will be collected from electronic medical records at each participating site and centrally coordinated and analyzed at the trial coordinating center.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Ayşenur Dostbil
Study Contact Backup
- Name: Yasin Tire
- Phone Number: +905055367970
- Email: dryasintire@hotmail.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Written informed consent
- Age ≥ 18 years
- ASA physical status I, II, or III
- Scheduled for elective non-cardiac abdominal surgery with expected surgery duration ≥ 2 h-hours
- General anesthesia
- Planned hospital stay of at least 48 hours
Exclusion Criteria:
- Pregnant or nursing (breastfeeding) women
- Neurologic deficit or chronic pain disease
- Planned use of regional anesthesia techniques for postoperative pain
- Emergency surgery
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Acetaminophen
Arm 1: Acetaminophen (Arm Type: Experimental) Participants will receive oral acetaminophen 1000 mg, administered 30 minutes before surgery and every 6 hours postoperatively for 48 hours. |
Intervention 1: Acetaminophen (Type: Drug) Oral acetaminophen 1000 mg tablet, administered 30 minutes before surgery and every 6 hours postoperatively until 48 hours after surgery. Other Name(s): Paracetamol Intervention 2: Placebo (Type: Other / Drug) Oral placebo tablet, visually identical to the acetaminophen tablet, administered on the same schedule (30 minutes before surgery and every 6 hours postoperatively until 48 hours after surgery).
Other Names:
|
|
Placebo Comparator: Placebo
Participants will receive a matching placebo tablet, administered 30 minutes before surgery and every 6 hours postoperatively for 48 hours.
|
Intervention 1: Acetaminophen (Type: Drug) Oral acetaminophen 1000 mg tablet, administered 30 minutes before surgery and every 6 hours postoperatively until 48 hours after surgery. Other Name(s): Paracetamol Intervention 2: Placebo (Type: Other / Drug) Oral placebo tablet, visually identical to the acetaminophen tablet, administered on the same schedule (30 minutes before surgery and every 6 hours postoperatively until 48 hours after surgery).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Total Postoperative Opioid Consumption
Time Frame: 48 hours after surgery
|
Cumulative opioid consumption during the first 48 postoperative hours, expressed as intravenous morphine milligram equivalents (MME).
Tramadol consumption will be converted using a potency equivalence factor of 0.15 relative to morphine.
|
48 hours after surgery
|
|
Average Postoperative Pain Score
Time Frame: 48 hours after surgery
|
Average postoperative pain intensity assessed using a 0-10 Visual Analog Scale (VAS), with 0 indicating no pain and 10 indicating the worst pain.
Pain will be assessed every 30 minutes during the first 2 hours in the recovery area, then approximately every 6 hours thereafter until 48 hours postoperatively.
|
48 hours after surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Patient Satisfaction with Postoperative Pain Management
Time Frame: 24 and 48 hours after surgery
|
Patient-reported satisfaction with postoperative pain management, assessed at 24 and 48 hours postoperatively using the question: "How do you rate your pain management?" on a 0-10 scale, where 0 = very bad and 10 = excellent.
|
24 and 48 hours after surgery
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Composite Opioid-Related Symptom Distress
Time Frame: 48 hours after surgery
|
Composite score of opioid-related side effects assessed using the Opioid-Related Symptom Distress Scale (ORSDS), evaluating 12 symptoms (nausea, vomiting, constipation, difficulty passing urine, difficulty concentrating, drowsiness, dizziness, confusion, fatigue, itchiness, dry mouth, and headache) across three dimensions (frequency, severity, bothersomeness), each scored 0-4.
The composite ORSDS is the mean of all 12 symptom-specific scores, with possible scores ranging from 0 to 4.
|
48 hours after surgery
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Study Aceta
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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