## Protocol Section
### Identification Module
**NCT ID:** NCT04254679

**Brief Title:** Pilot Trial: Postoperative Opioid-free Analgesia

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

#### Organization Study ID Info
**ID:** MUHC REB 2020-5965
#### Organization
**Class:** OTHER
**Full Name:** McGill University Health Centre/Research Institute of the McGill University Health Centre
### Status Module
#### Completion Date
**Date:** 2020-12-03

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-02-24

**Type:** ACTUAL

**Last Update Submit Date:** 2021-02-22

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2020-09-20

**Type:** ACTUAL

#### Start Date
**Date:** 2020-01-29

**Type:** ACTUAL

**Status Verified Date:** 2021-02

#### Study First Post Date
**Date:** 2020-02-05
**Type:** ACTUAL
**Study First Submit Date:** 2020-01-30
**Study First Submit QC Date:** 2020-01-31
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Society of American Gastrointestinal and Endoscopic Surgeons

#### Lead Sponsor

**Class:** OTHER

**Name:** McGill University Health Centre/Research Institute of the McGill University Health Centre

#### Responsible Party

**Investigator Affiliation:** McGill University Health Centre/Research Institute of the McGill University Health Centre

**Investigator Full Name:** Julio F Fiore Jr

**Investigator Title:** Assitant Professor (McGill)

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Outpatient Surgery

- Abdominal Surgery

- Breast Surgery

**Keywords:**

- Opioids

- Surgery

- Postoperative Period

- Postoperative Pain

- Analgesia

- Pain Management

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** This study will be a parallel, two-group, assessor-blind, pilot randomized trial.

##### Masking Info

**Masking:** SINGLE

**Masking Description:** Patient-reported outcomes and treatment adherence data will be collected via self-administered electronic questionnaires distributed using REDCap (http://project-redcap.org/) and completed by patients via smartphone, tablet or personal computer. Electronic outcome data will be transmitted directly to the REDCap database and verified by a blinded assessor. Adherence data will be verified by unblinded study staff. Patients who are not computer savvy, have limited access or prefer non-electronic assessment will complete the questionnaires via telephone interviews with a blinded assessor; in this case, data will be recorded in paper forms and subsequently transferred to the REDCap database. Outcome data that are not patient-reported (e.g. postoperative complications, unplanned healthcare utilization, chronic opioid use), will be obtained from medical records by a blinded assessor.

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 81

**Type:** ACTUAL

**Phases:**

- PHASE2

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Opioid analgesics

**Label:** Opioid analgesia

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: Non-opioid analgesics

**Label:** Opioid-free analgesia

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Opioid analgesia

**Description:** 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.

**Name:** Opioid analgesics

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Opioid-free analgesia

**Description:** 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.

**Name:** Non-opioid analgesics

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** At least 70% of patient undergoing the outpatient general surgery procedures of interest are eligible to be randomized.

**Measure:** Feasibility: Rate of eligibility

**Time Frame:** 4 months

**Description:** At least 90% of the surgeons who agreed to have their patients randomized will comply with the agreement (i.e. not change their minds).

**Measure:** Feasibility: Rate of acceptability of the trial by surgeons

**Time Frame:** 4 months

**Description:** At least 50% of eligible patients agree to participate in the study and are randomized.

**Measure:** Feasibility: Rate of recruitment (acceptability of the trial by patients)

**Time Frame:** 4 months

**Description:** At least 80% of the randomized patients comply with their allocated treatment (i.e. will take their pain medications as prescribed).

**Measure:** Feasibility: Rate of treatment compliance

**Time Frame:** 4 months

**Description:** At least 80% of the patients randomized complete outcome assessment at 30-days after surgery.

**Measure:** Feasibility: Rate of follow-up compliance

**Time Frame:** 4 months

**Description:** 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).

**Measure:** Feasibility: Rate of missing questionnaire data

**Time Frame:** 4 months

#### Secondary Outcomes

**Description:** 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.

**Measure:** Postoperative pain

**Time Frame:** 30 days.

**Description:** The time to the first report of stopping the use of pain medication.

**Measure:** Time to stopping pain medication

**Time Frame:** 30 days.

**Description:** 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.

**Measure:** Postoperative health status

**Time Frame:** Weeks 1, 2, 3 and 4 after surgery.

**Description:** 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.

**Measure:** Opioid side-effects

**Time Frame:** Postoperative days 1 to 7, weeks 2, 3 and 4 after surgery

**Description:** 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.

**Measure:** Rate of opioid misuse

**Time Frame:** 4 weeks

**Description:** Classified according to Clavien-Dindo and transformed into the Comprehensive Complication Index. Scores range from 0 (no complication) to 100 (death).

**Measure:** Postoperative complications (index)

**Time Frame:** 30 days.

**Description:** Emergency department visits, hospital readmissions.

**Measure:** Rate of unplanned healthcare utilization

**Time Frame:** 30 days.

**Description:** 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.

**Measure:** Rate of adverse drug events

**Time Frame:** 30 days.

**Description:** Filling of opioid prescriptions up to 3 months after surgery.

**Measure:** Rate of prolonged opioid use

**Time Frame:** 3 months

### Eligibility Module

**Eligibility Criteria:** 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

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Montreal

**Country:** Canada

**Facility:** McGill University Health Centre

**State:** Quebec

**Zip:** H3G 1A4

### References Module

#### References

**Citation:** 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.

**PMID:** 35849399

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M13069

- Name: Pain, Postoperative

- Relevance: LOW

- As Found: Unknown

- ID: M13066

- Name: Pain

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Ancestors

- ID: D000009294

- Term: Narcotics

- ID: D000002492

- Term: Central Nervous System Depressants

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Analg

- Name: Analgesics

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Antipy

- Name: Antipyretics

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

### Intervention Browse Module - Browse Leaves

- ID: M4032

- Name: Analgesics

- Relevance: HIGH

- As Found: Buprenorphine

- ID: M2340

- Name: Acetaminophen

- Relevance: LOW

- As Found: Unknown

- ID: M4033

- Name: Analgesics, Opioid

- Relevance: HIGH

- As Found: SVT

- ID: M20786

- Name: Analgesics, Non-Narcotic

- Relevance: HIGH

- As Found: Tcells

- ID: M12245

- Name: Narcotics

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000000701

- Term: Analgesics, Opioid

- ID: D000000700

- Term: Analgesics

- ID: D000018712

- Term: Analgesics, Non-Narcotic

### Misc Info Module

#### Submission Tracking

- Estimated Results First Submit Date: 2024-03-22

##### Submission Infos

- MCP Release N: Unknown

- Release Date: 2024-03-22

- Reset Date: Unknown

- Unrelease Date: Unknown

- Unrelease Date Unknown: Unknown

- Version Holder: 2024-05-24
