Pilot Trial: Postoperative Opioid-free Analgesia

Opioid-free Analgesia After Outpatient General Surgery: A Pilot Randomized Controlled Trial

North America is facing an opioid epidemic fueled by surgeons, who are the second largest subgroup of physicians involved in opioid prescribing. Surgery often serves as the initial event for opioid-naïve patients to obtain a prescription for opioids and spiral into misuse and addiction. From the perspective of perioperative care clinicians, the answer to the opioid crisis may be using opioid-free analgesia. However, the number of comparative studies in this field is limited and existing small trials do not reflect current standards of care in North America. Lack of evidence means that the decision to prescribe opioids after outpatient surgery largely depends on surgeon preference and healthcare culture. Hence, there is an urgent need for a robust randomized controlled trial (RCT) to guide clinical decision-making. The feasibility and optimal design of this RCT should be informed by a pilot trial. The overarching goal of this pilot RCT is to investigate the feasibility of conducting a full-scale RCT to assess the comparative-effectiveness of opioid versus opioid-free analgesia after outpatient general surgery.

Study Overview

• Status: Completed
• Conditions: Breast Surgery; Abdominal Surgery; Outpatient Surgery
• Intervention / Treatment: Drug: Opioid analgesics; Drug: Non-opioid analgesics

Detailed Description

This study will be a pragmatic, parallel, two-group, assessor-blind, pilot RCT. The investigators aim to recruit 80 adult patients at two tertiary hospitals in Montreal. Eligibility criteria will span outpatient procedures in abdominal and breast surgery. Patients are randomized on a 1:1 ratio to treatment with either opioid (standard care) or without opioid (only non-opioid analgesics). Patients will be followed up for 3 months after surgery; postoperative day (POD) 1 to POD 7 and at 2, 3 and 4 weeks after surgery, and at 3 months. Assessments will include postoperative pain, physical and mental function, adverse drug events, prolonged opioid use and opioid misuse. Feasibility outcomes will include the number of patients screened, consented and randomized, adherence with treatment and completion of follow-up. Data from this pilot study will inform the calculation of sample size requirements for the full-scale RCT. An embedded qualitative study will be conducted to help optimize trial design based on clinicians' and patients' perspective.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Adult patients (>18 yo) undergoing outpatient surgery

• Abdominal surgery (i.e. cholecystectomies, hernia repairs, ovarian cystectomies, salpingectomies)
• Breast surgery (i.e. lumpectomies, partial and complete mastectomies, axillary node dissections)

Exclusion Criteria:

All patients

• Intraoperative or early postoperative complications (i.e. diagnosed in the Post-Anesthesia Care Unit (PACU)) that require postoperative hospital stay
• Contraindications to any of the drugs used in the trial
• Difficult to be reached after surgery
• Inability to provide written informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Opioid analgesia	Drug: Opioid analgesics; Current standard of care in the participating centers Prescription of around-the-clock non-opioid analgesics (acetaminophen and/or NSAIDs/COX-2) and a supply of opioids to be used as a rescue in case of breakthrough pain. The specific round-the-clock analgesia and rescue opioid regimens will be determined by the patient's primary surgeon considering the surgical procedure, comorbidities and patient's preference.
Active Comparator: Opioid-free analgesia	Drug: Non-opioid analgesics; Prescription of around-the-clock non-opioid analgesics (acetaminophen alone or combined with NSAIDs/COX-2). The specific non-opioid analgesia regimens will be determined by the patient's primary surgeon considering the surgical procedure, comorbidities and patient's preference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Screened Participants Who Were Eligible to Participate in the Study	At least 70% of patients undergoing the outpatient general surgery procedures of interest (screened participants) are eligible to be randomized.	4 months
Percentage of Surgeons Agreeing and Adhering to Patient Randomization	At least 90% of the surgeons who agreed to have their patients randomized comply with the agreement (i.e. not change their minds).	4 months
Percentage of Eligible Patients Agreeing to Participate	At least 50% of eligible patients agree to participate in the study and are randomized.	4 months
Percentage of Randomized Patients Complying With Allocated Treatment	At least 80% of the randomized patients comply with their allocated treatment (i.e. will take their pain medications as prescribed).	4 months
Percentage of Randomized Patients Completing the 30-day Postoperative Outcome Assessment	At least 80% of the randomized patients complete outcome assessment at 30 days after surgery.	4 months
Percentage of Missing Data Among All Questionnaires Distributed to Patients Who Completed the Assessments	Among all questionnaires distributed to patients who complete outcome assessments, the proportion of missing data (i.e. non-response to questionnaires) is less than 10%.	4 months
Percentage of Missing Data Among All Questionnaire Items Distributed to Patients Who Completed the Assessments	Among patients who complete outcome assessments, the proportion of missing data is less than 10% (i.e. non-response to specific questionnaire items).	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain	Measured using the Brief Pain Inventory Short-Form, which addresses pain severity and interference in the last 24 hours. Scores range from 0 to 10; higher scores represent worse pain outcomes.	30 days.
Time to Stopping Pain Medication	The time to the first report of stopping the use of pain medication.	30 days.
Postoperative Health Status	Measured using the PROMIS-29 questionnaire, which assesses 7 domains of health (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain interference). Norm-based scores are calculated for each domain, such that a score of 50 represents the mean of the general population (standard deviation=10). Higher scores represent more of the domain being measured.	Weeks 1, 2, 3 and 4 after surgery.
Opioid Side-effects	Measured using the Perioperative Opioid-Related Symptom Distress Scale, which records symptom distress due to common adverse effects experienced by patients who receive opioids to relieve postoperative pain. The reported rates indicate the number of reported events per period of evaluation.	Postoperative days 1 to 7, weeks 2, 3 and 4 after surgery
Rate of Opioid Misuse	Measured using the Prescription Opioid Misuse Index, which includes questions regarding excessive dose, frequency of use, need for early refills, feeling high from the medication, taking the medication due to stress and obtaining prescriptions from multiple physicians. Scores range from 0 to 6; an affirmative answer to >1 question indicates the patient exhibits prescription opioid misuse.	4 weeks
Postoperative Complications Classification	Graded by severity using the Dindo-Clavien classification. This system grades complications according to the therapy needed for treatment (grades I to IV, best to worse). Grade I: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Grade II: Complications requiring drug treatments other than those allowed for Grade I complications; this includes blood transfusion and total parenteral nutrition (TPN) Grade III: Complications requiring surgical, endoscopic or radiological intervention Grade IIIa - intervention not under general anaesthetic Grade IIIb - intervention under general anaesthetic	30 days.
Rate of Unplanned Healthcare Utilization	Emergency department visits, hospital readmissions.	30 days.
Rate of Adverse Drug Events	Obtained from spontaneous patient reporting (Trigger question "Did you have any significant medical problem related or unrelated to your surgery since the last study assessment?"). Events were coded using the MedDRA coding dictionary, graded by severity according to the Common Terminology Criteria for Adverse Events (CTCAE) and assessed for potential causality using the WHO/UMC system.	30 days after surgery
Rate of Prolonged Opioid Use	Filling of opioid prescriptions up to 3 months after surgery.	3 months
Comprehensive Complication Index at 30-day	Measured using the Comprehensive Complication Index score at 30 after surgery. The score ranges from 0 to 100; higher scores indicate greater severity of complications.	30 days

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Society of American Gastrointestinal and Endoscopic Surgeons

Publications and helpful links

General Publications

• Do U, El-Kefraoui C, Pook M, Balvardi S, Barone N, Nguyen-Powanda P, Lee L, Baldini G, Feldman LS, Fiore JF Jr; McGill Better Opioid Prescribing Collaboration; Alhashemi M, Antoun A, Barkun JS, Brecht KM, Chaudhury PK, Deckelbaum D, Di Lena E, Dumitra S, Elhaj H, Fata P, Fleiszer D, Fried GM, Grushka J, Kaneva P, Khwaja K, Lapointe-Gagner M, McKendy KM, Meguerditchian AN, Meterissian SH, Montgomery H, Rajabiyazdi F, Safa N, Touma N, Tremblay F. Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial. JAMA Netw Open. 2022 Jul 1;5(7):e2221430. doi: 10.1001/jamanetworkopen.2022.21430.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Actual): September 20, 2020
• Study Completion (Actual): December 3, 2020

Study Registration Dates

• First Submitted: January 30, 2020
• First Submitted That Met QC Criteria: January 31, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Postoperative Pain; Surgery; Analgesia; Opioids; Postoperative Period; Pain Management
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Narcotics; Analgesics, Opioid; Analgesics; Analgesics, Non-Narcotic
• Other Study ID Numbers: MUHC REB 2020-5965

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No