Perioperative Pregabalin for Reducing Opioid Consumption After Cardiac Surgery

Study Overview
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Brief Summary
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OPIATE is a double-blinded randomized controlled trial (RCT) comparing pregabalin in addition to usual care to usual care alone for reducing post-operative opioid consumption in patients undergoing on-pump cardiac surgery. Patients will be randomized in a 1:1 ratio to receive either pregabalin (300 mg pre-operatively + 75 mg post-operatively twice daily until discharge or 5 days) in addition to usual care or matching placebos in addition to usual care. The aim of the trial is to show that pregabalin is superior to usual care (i.e. a superiority trial).

Detailed Description
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By administering oral pregabalin to patients before and after cardiac surgery for pain relief, we aim to reduce the amount of opioids they will require for pain relief and reduce opioid-related side effects that they may experience after surgery. Participants will be randomly assigned to receive either pregabalin in addition to usual care or usual care alone. Participants in the pregabalin group will receive two 150 mg pregabalin capsules (300 mg total dose) within 2 hours before surgery and a 75 mg pregabalin capsule twice daily after surgery until discharge from hospital to a maximum of 5 days after surgery. Participants in the usual care group will receive two placebo study capsules within 2 hours before surgery and a placebo capsule twice daily after surgery until discharged from hospital to a maximum of 5 days after surgery. OPIATE will be the largest clinical trial of pregabalin in cardiac surgery with results that are expected to set new post-operative pain management guidelines to encourage the widespread use of pregabalin in cardiac patients.

Official Title
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Peri-Operative Pregabalin for Reducing opIoid Consumption AfTer Cardiac surgEry: A Randomized Trial

Conditions
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Opioid Use

Intervention / Treatment
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* Drug: Pregabalin 300 mg
* Drug: Pregabalin 75 mg
* Drug: Pregabalin 300 mg Placebo
* Drug: Pregabalin 75 mg Placebo
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age Undergoing cardiac surgery with median sternotomy Provide written informed consent Exclusion Criteria: Use of opioids or cannabis products in the past 30 days Daily use of pregabalin or gabapentin within 7 days of randomization Intravenous drug user Have a hypersensitivity or allergy to pregabalin History of previous cardiac surgery Undergoing minimally invasive surgery Emergency surgery Severe renal impairment (creatinine > 250 μmol/L) Unable to swallow study medications Pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blinded randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin + Usual Care<br>300 mg pregabalin taken orally within 2 hours before surgery and 75 mg pregabalin taken orally twice daily after surgery beginning after successful extubation (day after surgery or later) until discharge or 5 days, whichever comes first. Participants will also receive standard pain management. | Drug: Pregabalin 300 mg<br>* Pregabalin 300 mg, capsule<br>* Other names: Lyrica;Drug: Pregabalin 75 mg<br>* Pregabalin 75 mg twice daily, capsules<br>* Other names: Lyrica;Other: Usual Care<br>* Usual Care<br>|
| Placebo Comparator: Placebo + Usual Care<br>Placebo taken orally within 2 hours before surgery and placebo taken orally twice daily after surgery beginning after successful extubation (day after surgery or later) until discharge or 5 days, whichever comes first. Participants will also receive standard pain management. | Drug: Pregabalin 300 mg Placebo<br>* Placebo, matching Pregabalin 300 mg capsule<br>* Other names: Placebo Capsule;Drug: Pregabalin 75 mg Placebo<br>* Placebo, matching Pregabalin 75 mg capsules<br>* Other names: Placebo Capsule;Other: Usual Care<br>* Usual Care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative opioid consumption | Dose of opioids consumed (in morphine equivalents) by participants | After surgery until discharge from hospital or 5 days, whichever is first. | 
| Daily opioid consumption | Dose of opioids consumed (in morphine equivalents) by participants | Each postoperative day, beginning on postoperative day 1 and ending on the day of discharge from hospital or postoperative day 5, whichever is first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily postoperative pain | Acute postoperative pain assessed by the numeric rating scale (NRS; 0 to 10) | Each postoperative day, beginning on postoperative day 1 and ending on the day of discharge from hospital or postoperative day 5, whichever is first. | 
| Average postoperative pain | Acute postoperative pain assessed by the numeric rating scale (NRS; 0 to 10) | Average of scores after surgery until discharge from hospital or 5 days, whichever is first. | 
| Cumulative consumption of antiemetic medications | Dose of gravol or ondansetron consumed by participants | After surgery until discharge from hospital or 5 days, whichever is first. | 
| Daily consumption of antiemetic medications | Dose of gravol or ondansetron consumed by participants | Each postoperative day, beginning on postoperative day 1 and ending on the day of discharge from hospital or postoperative day 5, whichever is first. | 
| Time to extubation | Time from surgery completion until first successful extubation | Within the first 5 days after surgery | 
| Mobility | Proportion of mobility goals met after surgery | Within the first 5 days after surgery | 
| Delirium | Number of participants meeting the Confusion Assessment Method (CAM) criteria | Starting the second day after surgery and ending after 5 days or 3 days of negative tests. | 
| Major adverse cardiovascular events | The first occurrence of death, non-fatal myocardial infarction (MI) or non-fatal stroke | Within the first 5 days after surgery | 
| Death | Number of participants experiencing death from any cause | Within the first 5 days after surgery | 
| Myocardial infarction | Number of participants experiencing myocardial infarction (MI) without death | Within the first 5 days after surgery | 
| Stroke | Number of participants experiencing stroke without death | Within the first 5 days after surgery |