Acetaminophen vs Placebo for Postoperative Analgesia After Abdominal Surgery

August 22, 2026 updated by: Yasin Tire, MD, Konya City Hospital

Comparison of Placebo and Acetaminophen on Postoperative Opioid Consumption in Non-Cardiac Abdominal Surgery

This study investigates whether oral acetaminophen, when added to standard pain management, reduces opioid use and pain after major abdominal surgery, compared to a placebo (inactive pill). Patients undergoing planned abdominal surgery under general anesthesia will be randomly assigned to receive either acetaminophen or a placebo tablet before surgery and every 6 hours afterward for 48 hours, in addition to their usual pain medication. Researchers will measure how much opioid pain medication patients need, how much pain they report, and how satisfied they are with their pain control during the first two days after surgery. The goal is to determine whether oral acetaminophen provides a genuine benefit beyond placebo in reducing opioid use while maintaining adequate pain control.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1504

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Ayşenur Dostbil

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Acetaminophen

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
Placebo Comparator: Placebo
Participants will receive a matching placebo tablet, administered 30 minutes before surgery and every 6 hours postoperatively for 48 hours.
Drug: Acetaminophen

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Konya City Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Erzurum Regional Training & Research Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 5, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 15, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 27, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 22, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 25, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Study Aceta

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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