Opioid-Free vs Opioid Analgesia for Postoperative Pain

(PAIN-Alt Trial)

Overseen By Karine Roversi, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

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

Must not be taking: Opioids

Disqualifiers: Breast reconstruction, Opioid use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 4 weeks

540 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking opioids before the surgery, you cannot participate in the trial.

What data supports the effectiveness of the treatment Opioid-Free Analgesia (OFA) for postoperative pain?

Research suggests that Opioid-Free Analgesia (OFA) can lead to lower pain scores and fewer side effects compared to traditional opioid use after surgery. It has been shown to improve patient recovery and satisfaction while reducing healthcare costs. ^{1 2 3 4 5}

Is opioid-free analgesia generally safe for humans?

Opioid-free analgesia (OFA) is generally considered safe and can reduce some side effects associated with opioids, like nausea and sedation, but more data is needed to fully understand its safety profile. ^{1 4 5 6 7}

How does opioid-free analgesia (OFA) differ from opioid analgesia (OA) for postoperative pain management?

Opioid-free analgesia (OFA) is unique because it avoids the use of opioids entirely, reducing the risk of opioid addiction and side effects. Instead, it uses a combination of non-opioid medications and techniques, such as local anesthetics, NSAIDs (non-steroidal anti-inflammatory drugs), and other adjuvants, to manage pain effectively. ^{1 2 8 9 10}

Research Team

Julio Flavio Fiore, PhD

Principal Investigator

McGill University

Eligibility Criteria

This trial is for patients having outpatient breast surgery (mastectomy or lumpectomy) for cancerous or non-cancerous conditions, with plans to go home the same day. It's not specified who can't join.

Inclusion Criteria

I am having surgery for breast cancer or a non-cancerous breast condition.

I am expected to go home the same day as my surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either opioid or non-opioid analgesia after outpatient breast surgery

4 weeks

Weekly follow-ups for 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Monthly visits for 6 months

Long-term follow-up

Assessment of chronic postsurgical pain and persistent opioid use

6 months

Treatment Details

Interventions

• Opioid Analgesia (OA)
• Opioid-Free Analgesia (OFA)

Trial Overview The study compares post-surgery pain management: one group receives opioid drugs and the other gets only non-opioid alternatives. The focus is on pain control effectiveness and side effects of each method.

Participant Groups

Group I: Opioid-Free Analgesia (OFA) Experimental Treatment 1 Intervention

Group II: Opioid Analgesia (OA) Active Control 1 Intervention

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

In a study of 10,219 surgical patients across 187 hospitals, opioid-free analgesia (OFA) was found to be underutilized, especially among patients with obesity and depression, who were less likely to receive OFA despite being at higher risk for opioid-related adverse events.

Older patients and those with neurological disorders, diabetes, or psychosis were more likely to receive OFA, indicating that hospital policies and practices significantly influence the adoption of opioid-free pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of predictors of opioid-free analgesia for management of acute post-surgical pain in the United States. Urman, RD., Böing, EA., Khangulov, V., et al.[2019]

This pilot randomized clinical trial successfully demonstrated the feasibility of comparing opioid analgesia (OA) and opioid-free analgesia (OFA) in 76 patients after outpatient surgery, fulfilling all pre-defined feasibility criteria.

The study found that 99% of participants adhered to their assigned treatment, indicating strong compliance, which supports the potential for a larger trial to evaluate the effectiveness of these pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial. Do, U., El-Kefraoui, C., Pook, M., et al.[2022]

Opioid-free analgesia (OFA) multimodal analgesia (MMA) strategies have shown promise in reducing opioid use during perioperative care, leading to improved pain control and higher patient satisfaction.

Implementing OFA strategies can enhance patient recovery and lower healthcare costs, but widespread adoption is still in the early stages and requires tailored approaches to meet individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving the management of acute perioperative pain towards opioid free protocols: a narrative review. Nassif, GJ., Miller, TE.[2020]

In a study of 60 patients undergoing elective laparoscopic cholecystectomy, opioid-free anesthesia (OFA) resulted in significantly lower pain scores and reduced opioid requirements compared to traditional anesthesia with fentanyl, particularly noted at 1 and 24 hours post-surgery.

The OFA group reported no severe pain (scores of 7-10 on the Visual Analogue Scale) at 24 hours after surgery, demonstrating that OFA is a safe and effective alternative that minimizes opioid-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Opioid-Free General Anesthesia More Superior for Postoperative Pain Versus Opioid General Anesthesia in Laparoscopic Cholecystectomy? Toleska, M., Dimitrovski, A.[2022]

The POFA trial is a large-scale study involving 400 patients to evaluate the effectiveness of opioid-free anaesthesia (OFA) in reducing severe postoperative opioid-related adverse events after major or intermediate non-cardiac surgery.

The primary outcome will assess the occurrence of adverse events like hypoxaemia, ileus, or cognitive dysfunction within 48 hours post-surgery, aiming to demonstrate that OFA leads to fewer complications compared to standard anaesthesia protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery. Beloeil, H., Laviolle, B., Menard, C., et al.[2019]

Opioid-free anesthesia (OFA) showed lower pain scores and reduced morphine consumption at 2 and 24 hours post-surgery compared to opioid-based anesthesia, but these differences were not clinically significant.

A significant benefit of OFA was observed in reducing postoperative nausea and vomiting (PONV), with a relative risk reduction indicating a much lower incidence of PONV in the OFA group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid-Free Anesthesia Benefit-Risk Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Salomé, A., Harkouk, H., Fletcher, D., et al.[2021]

In a study of 124 patients undergoing video-assisted lung surgery, opioid-free anesthesia (OFA) resulted in significantly lower pain severity during coughs on the first postoperative day compared to opioid-sparing anesthesia (OSA), with a VAS score of 1.88 versus 2.16.

The OFA group also experienced significantly fewer patient-controlled epidural analgesia (PCEA)-related adverse events, with only 19.6% of patients reporting issues compared to 47.3% in the OSA group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid-free anesthesia reduces the severity of acute postoperative motion-induced pain and patient-controlled epidural analgesia-related adverse events in lung surgery: randomized clinical trial. Wang, S., Li, Y., Liang, C., et al.[2023]

In a study of 521 patients undergoing laparoscopic hysterectomy, Opioid-Free Anaesthesia (OFA) was found to be feasible and did not result in higher pain scores compared to traditional opioid-based anaesthesia, indicating its effectiveness in managing postoperative pain.

Patients receiving OFA used significantly less morphine equivalent during the procedure, suggesting that OFA can effectively reduce opioid consumption without compromising pain management or increasing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Intraoperative Opioids Avoidance A Utopia? A Matched Study in Laparoscopic Hysterectomy. Forget, P., De Kock, M., Lovqvist, L., et al.[2022]

In a study of 311 patients undergoing major surgeries, a total intravenous opioid-free anesthesia (OFA) protocol was successfully implemented, resulting in minimal use of IV morphine (only 2 mg on average) during recovery, indicating effective pain management without opioids.

The findings suggest that OFA is a safe and feasible approach, as it effectively managed the physiological stress responses during surgery and required very low opioid consumption in the postoperative period, supporting a shift away from traditional opioid-based anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons from the Analysis of a Retrospective Cohort of Patients Who Underwent Large Open Abdominal Surgery Under Total Intravenous Opioid-Free Anesthesia. Estebe, JP., Morel, M., Daouphars, T., et al.[2021]

Opioid-free anaesthesia (OFA) is a technique that avoids the use of opioids during surgery, which has shown benefits, particularly for patients who are morbidly obese or have sleep apnoea, as supported by various studies and case reports.

OFA employs alternative methods such as non-opioid adjuvants (like NSAIDs and local anaesthetics) and techniques like dexmedetomidine and low-dose ketamine to manage pain, potentially reducing the risk of postoperative complications like hyperalgesia and chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Special indications for Opioid Free Anaesthesia and Analgesia, patient and procedure related: Including obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, opioid addiction and cancer surgery. Sultana, A., Torres, D., Schumann, R.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Analysis of predictors of opioid-free analgesia for management of acute post-surgical pain in the United States. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Evolving the management of acute perioperative pain towards opioid free protocols: a narrative review. [2020]

4. North Macedonia pubmed.ncbi.nlm.nih.gov

Is Opioid-Free General Anesthesia More Superior for Postoperative Pain Versus Opioid General Anesthesia in Laparoscopic Cholecystectomy? [2022]

5. England pubmed.ncbi.nlm.nih.gov

POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Opioid-Free Anesthesia Benefit-Risk Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Opioid-free anesthesia reduces the severity of acute postoperative motion-induced pain and patient-controlled epidural analgesia-related adverse events in lung surgery: randomized clinical trial. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Is Intraoperative Opioids Avoidance A Utopia? A Matched Study in Laparoscopic Hysterectomy. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Lessons from the Analysis of a Retrospective Cohort of Patients Who Underwent Large Open Abdominal Surgery Under Total Intravenous Opioid-Free Anesthesia. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Special indications for Opioid Free Anaesthesia and Analgesia, patient and procedure related: Including obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, opioid addiction and cancer surgery. [2018]