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

Official title

Comparative Effectiveness of Opioid Versus Opioid-free Post-discharge Analgesia After Outpatient Breast Surgery: A Protocol for a Randomized Controlled Trial (PAIN-Alt Trial)

Overview

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.

Interventions

• Other Opioid Analgesia (OA) [Multimodal analgesia including opioid drugs]
  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 tria
• Other Opioid-Free Analgesia (OFA) [Multimodal analgesia not including opioid drugs]
  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 det

Primary outcome measures

• Pain intensity [Time frame: Postoperative days 1 to 7.]
• Pain interference [Time frame: Postoperative days 1 to 7.]

Secondary outcome measures (9)

• Adverse drug events [Time frame: Up to 30 days after surgery.]
• Time to stopping pain medication [Time frame: Up to 30 days after surgery.]
• Physical and Mental Health Status [Time frame: Postoperative weeks 1, 2, 3, and 4, postoperative month 3 and 6.]
• Opioid misuse [Time frame: Postoperative weeks 1, 2, 3, and 4, postoperative month 3 and 6.]
• Satisfaction with pain management [Time frame: Postoperative day 7.]
• 30-day postoperative complications [Time frame: Up to 30 days after surgery.]
• 30-day unplanned healthcare utilization [Time frame: Up to 30 days after surgery.]
• Chronic postsurgical pain [Time frame: Up to 6 months after surgery.]
• Persistent opioid use [Time frame: Up to 6 months after surgery.]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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 \[e.g., lack of support at home\]).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• McGill University Health Centre (Glen Site) — Montreal

Publications

• 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)005 PMID 35717988
• 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 PMID 31563269
• 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, Montgomer PMID 35849399
• 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. PMID 35918552
• 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 b PMID 41193191

Identifiers

NCT: NCT06507345 · 2024-10253

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗