Postoperative Analgesia Intervention With Non-opioid Alternatives (PAIN-Alt) Trial - Breast Surgery

NCT06507345 | Recruiting DMC

• 1 other identifier: 2024-10253
• Study Type: interventional
• Target: 540
• Locations: 1 country
• Sites: 1

Brief Summary

North America is experiencing a crisis of opioid use and abuse, partially caused by excessive prescribing by doctors. People often receive their first opioid prescription for pain treatment after outpatient breast surgery (i.e., surgery to remove all or parts of the breast(s), where patients leave the hospital the same day). Many patients misuse these drugs and become addicted. Additionally, many of the opioid pills prescribed to patients are left unused and may be misused by family members, friends, or other community members. To prevent this problem, surgeons can avoid prescribing opioids by prioritizing opioid-free analgesia (i.e., pain treatment using only non-opioid interventions). Prescribing only non-opioid pain medications after surgery is very common in many countries outside of North America; however, few studies have assessed whether opioid-free analgesia is as effective as opioid analgesia after breast surgery. Therefore, the main question driving this study is: For patients who undergo outpatient breast surgery, is pain treatment without opioids as good as pain treatment with opioids? The proposed trial will compare two groups of patients: one group will receive opioids to treat pain after surgery, while the other group will receive only non-opioid medications. The impact of these different medication strategies will be measured on pain intensity, pain interference with daily activities, medication side effects, and other outcomes. An expert team of scientists, surgeons, pain specialists, nurses, and patients has been assembled to maximize the success of this study. The results will provide important information to guide surgeons' decisions to prescribe (or not to prescribe) opioids. If opioid-free analgesia is found to be effective, doctors may be able to substantially reduce opioid prescribing after breast surgery and prevent more people from misusing opioids.

Conditions

Post Operative Pain; Opioid Analgesic Adverse Reaction; Surgery; Postoperative Pain; Breast Disease

Keywords

Surgery; Postoperative analgesia; Breast surgery; Opioids; Postoperative pain; Postoperative care

Outcome Measures

Primary Outcomes (2)

• Pain intensity

  Pain intensity will be measured using the Brief Pain Inventory-Short Form (BPI), a self-reported pain questionnaire developed by the World Health Organization (WHO). In this questionnaire, pain intensity is measured across four domains (worst, least, on average, and currently). Aggregated scores of pain intensity range from 0-10, with higher scores representing worse outcomes.

  Postoperative days 1 to 7.

• Pain interference

  Pain interference will be measured using the Brief Pain Inventory-Short Form (BPI), a self-reported pain questionnaire developed by the World Health Organization (WHO). In this questionnaire, pain interference is measured across seven domains (mood, work, general activity, walking, relationships, enjoyment of life, and sleep). Aggregated scores of pain interference range from 0-10, with higher scores representing worse outcomes.

  Postoperative days 1 to 7.

Secondary Outcomes (9)

• Adverse drug events

  Up to 30 days after surgery.

• Time to stopping pain medication

  Up to 30 days after surgery.

• Physical and Mental Health Status

  Postoperative weeks 1, 2, 3, and 4, postoperative month 3 and 6.

• Opioid misuse

  Postoperative weeks 1, 2, 3, and 4, postoperative month 3 and 6.

• Satisfaction with pain management

  Postoperative day 7.

Study Arms (2)

Opioid Analgesia (OA)

ACTIVE COMPARATOR

Other: Opioid Analgesia (OA) [Multimodal analgesia including opioid drugs]

Opioid-Free Analgesia (OFA)

EXPERIMENTAL

Other: Opioid-Free Analgesia (OFA) [Multimodal analgesia not including opioid drugs]

Interventions

Opioid Analgesia (OA) [Multimodal analgesia including opioid drugs] OTHER

In line with current standard care, discharge prescriptions for this group will include around-the-clock non-opioid analgesics (acetaminophen and/or NSAIDs given at regularly scheduled intervals) and opioid tablets 'as needed' for breakthrough pain (i.e., pain that erupts while patients are already taking analgesics). Non-pharmacological pain interventions (i.e., icepacks, music, meditation.) may be recommended by some surgeons as part of standard practice. Given the pragmatic nature of the trial, the specific around-the-clock analgesia and rescue opioid regimens and other non-pharmacological interventions will be determined by the patient's surgeon discretion considering the breast procedure undertaken, co-morbidities, and patient preference.

Opioid Analgesia (OA)

Opioid-Free Analgesia (OFA) [Multimodal analgesia not including opioid drugs] OTHER

Discharge prescriptions for this group will include around-the-clock non-opioid analgesics (acetaminophen and/or NSAIDs). In case of breakthrough pain, rescue analgesia may be provided by (1) using evidence-based non-pharmacological pain interventions (i.e., icepacks, music, and meditation), (2) adding non-opioid drugs not included in the initial regimen, or (3) switching drugs targeting individual variances in analgesia response. The specific around-the-clock and rescue OFA regimens will be determined by the patient's surgeon considering the type of procedure, co-morbidities, and patient preference.

Opioid-Free Analgesia (OFA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergoing mastectomy (i.e., total, modified radical, radical, or skin/nipple sparing) or lumpectomy (i.e., excisional biopsy, partial or segmental mastectomy, oncoplastic breast-conserving surgery) for malignant (cancer) and non-malignant diseases (i.e., ductal carcinoma in situ)
• Planned discharge on the day of the operation.

You may not qualify if:

• Immediate breast reconstruction, i.e., implant, tissue-expander, or autologous/flap-based (often leads to higher levels of pain and analgesia requirements)
• Contraindications to the drugs used in the trial in accordance with Health Canada Monographs (i.e., opioid use disorder, pregnancy, breastfeeding, heart failure, allergy/hypersensitivity, peptic ulcer, bleeding disorders, renal or liver impairment)
• Taking opioids preoperatively
• Cognitive impairment precluding patient-reported outcome assessment
• Need for postoperative hospitalization decided before randomization (i.e., same-day discharge cancelled for medical \[e.g., intra-operative complications\] or non-medical reasons \[e.g., lack of support at home\]).

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

McGill University Health Centre (Glen Site)

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Related Publications (5)

• Fiore JF Jr, El-Kefraoui C, Chay MA, Nguyen-Powanda P, Do U, Olleik G, Rajabiyazdi F, Kouyoumdjian A, Derksen A, Landry T, Amar-Zifkin A, Bergeron A, Ramanakumar AV, Martel M, Lee L, Baldini G, Feldman LS. Opioid versus opioid-free analgesia after surgical discharge: a systematic review and meta-analysis of randomised trials. Lancet. 2022 Jun 18;399(10343):2280-2293. doi: 10.1016/S0140-6736(22)00582-7.

  PMID: 35717988 BACKGROUND

• Fiore JF Jr, Olleik G, El-Kefraoui C, Verdolin B, Kouyoumdjian A, Alldrit A, Figueiredo AG, Valanci S, Marquez-GdeV JA, Schulz M, Moldoveanu D, Nguyen-Powanda P, Best G, Banks A, Landry T, Pecorelli N, Baldini G, Feldman LS. Preventing opioid prescription after major surgery: a scoping review of opioid-free analgesia. Br J Anaesth. 2019 Nov;123(5):627-636. doi: 10.1016/j.bja.2019.08.014. Epub 2019 Sep 25.

  PMID: 31563269 BACKGROUND

• 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 BACKGROUND

• Do U, Pook M, Najafi T, Rajabiyazdi F, El-Kefraoui C, Balvardi S, Barone N, Elhaj H, Nguyen-Powanda P, Lee L, Baldini G, Feldman LS, Fiore JF; McGill Better Opioid Prescribing (MBOP) Collaboration. S110-Opioid-free analgesia after outpatient general surgery: A qualitative study focused on the perspectives of patients and clinicians involved in a pilot trial. Surg Endosc. 2023 Mar;37(3):2269-2280. doi: 10.1007/s00464-022-09472-8. Epub 2022 Aug 2.

  PMID: 35918552 BACKGROUND

• Fiore JF Jr, Shirzadi S, Roversi K, Prakash I, Wong S, Meterissian S, Meguerditchian AN, Desbiens C, Rivard J, Delisle M, Findlay-Shirras L, Abou Khalil J, Maciver A, Quan ML, Verreault K, Johnston S, Feldman L, McDonald EG; Postoperative Analgesia Intervention with Non-opioid Alternatives (PAIN-Alt) Collaboration. Comparative effectiveness of opioid versus opioid-free analgesia after outpatient breast surgery: PAIN-Alt trial protocol. BMJ Open. 2025 Nov 4;15(11):e107258. doi: 10.1136/bmjopen-2025-107258.

  PMID: 41193191 DERIVED

MeSH Terms

Conditions

Pain, Postoperative; Breast Diseases

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Julio Flavio Fiore, PhD

  McGill University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samin Shirzadi, MD, MPH

CONTACT

6475643377; samin.shirzadi@rimuhc.ca

Karine Roversi, PhD

CONTACT

4384935427; karine.roversi@rimuhc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Scientist

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: July 18, 2024
• Study Start: November 26, 2024
• Primary Completion: August 31, 2025
• Study Completion: February 28, 2026
• Last Updated: January 13, 2025

Record last verified: 2025-01

Locations

CA (1)