Pilot Trial: Postoperative Opioid-free Analgesia

Phase 2

Completed

Conditions: Outpatient Surgery
Breast Surgery
Abdominal Surgery

Interventions: Drug: Non-opioid analgesics
Drug: Opioid analgesics

Registration Number: NCT04254679

Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 81

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Opioid-free analgesia	Non-opioid analgesics	-
Opioid analgesia	Opioid analgesics	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Postoperative Pain	30 days.	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.
Time to Stopping Pain Medication	30 days.	The time to the first report of stopping the use of pain medication.
Postoperative Health Status	Weeks 1, 2, 3 and 4 after surgery.	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.
Opioid Side-effects	Postoperative days 1 to 7, weeks 2, 3 and 4 after surgery	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.
Rate of Opioid Misuse	4 weeks	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.
Postoperative Complications Classification	30 days.	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
Rate of Unplanned Healthcare Utilization	30 days.	Emergency department visits, hospital readmissions.
Rate of Adverse Drug Events	30 days after surgery	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.
Rate of Prolonged Opioid Use	3 months	Filling of opioid prescriptions up to 3 months after surgery.
Comprehensive Complication Index at 30-day	30 days	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.