Pilot Trial: Postoperative Opioid-free Analgesia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Outpatient Surgery, Abdominal Surgery, Breast Surgery

Intervention / Treatment
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* Drug: Opioid analgesics
* Drug: Non-opioid analgesics


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will be a parallel, two-group, assessor-blind, pilot randomized trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Opioid analgesia<br> | Drug: Opioid analgesics<br>* 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.<br>|
| Active Comparator: Opioid-free analgesia<br> | Drug: Non-opioid analgesics<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility: Rate of eligibility | At least 70% of patient undergoing the outpatient general surgery procedures of interest are eligible to be randomized. | 4 months | 
| Feasibility: Rate of acceptability of the trial by surgeons | At least 90% of the surgeons who agreed to have their patients randomized will comply with the agreement (i.e. not change their minds). | 4 months | 
| Feasibility: Rate of recruitment (acceptability of the trial by patients) | At least 50% of eligible patients agree to participate in the study and are randomized. | 4 months | 
| Feasibility: Rate of treatment compliance | At least 80% of the randomized patients comply with their allocated treatment (i.e. will take their pain medications as prescribed). | 4 months | 
| Feasibility: Rate of follow-up compliance | At least 80% of the patients randomized complete outcome assessment at 30-days after surgery. | 4 months | 
| Feasibility: Rate of missing questionnaire data | Among patients who complete outcome assessments, the proportion of missing data is less than 10% (i.e. non-response to questionnaires or 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. Scores range from 0 to 4; higher scores represent worse symptoms. | Postoperative days 1 to 7, weeks 2, 3 and 4 after surgery | 
| Rate of opioid misuse | Measured using the Prescription Opioid Abuse 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 (index) | Classified according to Clavien-Dindo and transformed into the Comprehensive Complication Index. Scores range from 0 (no complication) to 100 (death). | 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 will be 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. | 
| Rate of prolonged opioid use | Filling of opioid prescriptions up to 3 months after surgery. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioids, Surgery, Postoperative Period, Postoperative Pain, Analgesia, Pain Management