Perioperative Pregabalin for Reducing Opioid Consumption After Cardiac Surgery (OPIATE)

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

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).

Study Overview

• Status: Terminated
• Conditions: Opioid Use
• Intervention / Treatment: Other: Usual Care; Drug: Pregabalin 300 mg; Drug: Pregabalin 75 mg; Drug: Pregabalin 300 mg Placebo; Drug: Pregabalin 75 mg Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥ 18 years of age
2. Undergoing cardiac surgery with median sternotomy
3. Provide written informed consent

Exclusion Criteria:

1. Use of opioids or cannabis products in the past 30 days
2. Daily use of pregabalin or gabapentin within 7 days of randomization
3. Intravenous drug user
4. Have a hypersensitivity or allergy to pregabalin
5. History of previous cardiac surgery
6. Undergoing minimally invasive surgery
7. Emergency surgery
8. Severe renal impairment (creatinine > 250 μmol/L)
9. Unable to swallow study medications
10. Pregnant or breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregabalin + Usual Care; 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.	Other: Usual Care; Usual Care; Drug: Pregabalin 300 mg; Pregabalin 300 mg, capsule; Other Names: Lyrica; Drug: Pregabalin 75 mg; Pregabalin 75 mg twice daily, capsules; Other Names: Lyrica
Placebo Comparator: Placebo + Usual Care; 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.	Other: Usual Care; Usual Care; Drug: Pregabalin 300 mg Placebo; Placebo, matching Pregabalin 300 mg capsule; Other Names: Placebo Capsule; Drug: Pregabalin 75 mg Placebo; Placebo, matching Pregabalin 75 mg capsules; Other Names: Placebo Capsule

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: McMaster University
• Investigators: Principal Investigator: Andre Lamy, MD, MHSc, Hamilton Health Sciences Corporation

Publications and helpful links

General Publications

• Pesonen A, Suojaranta-Ylinen R, Hammaren E, Kontinen VK, Raivio P, Tarkkila P, Rosenberg PH. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. Br J Anaesth. 2011 Jun;106(6):873-81. doi: 10.1093/bja/aer083. Epub 2011 Apr 6.
• Joshi SS, Jagadeesh AM. Efficacy of perioperative pregabalin in acute and chronic post-operative pain after off-pump coronary artery bypass surgery: a randomized, double-blind placebo controlled trial. Ann Card Anaesth. 2013 Jul-Sep;16(3):180-5. doi: 10.4103/0971-9784.114239.
• Sundar AS, Kodali R, Sulaiman S, Ravullapalli H, Karthekeyan R, Vakamudi M. The effects of preemptive pregabalin on attenuation of stress response to endotracheal intubation and opioid-sparing effect in patients undergoing off-pump coronary artery bypass grafting. Ann Card Anaesth. 2012 Jan-Mar;15(1):18-25. doi: 10.4103/0971-9784.91473.
• Ziyaeifard M, Mehrabanian MJ, Faritus SZ, Khazaei Koohpar M, Ferasatkish R, Hosseinnejad H, Mehrabanian M. Premedication with oral pregabalin for the prevention of acute postsurgical pain in coronary artery bypass surgery. Anesth Pain Med. 2015 Jan 17;5(1):e24837. doi: 10.5812/aapm.24837. eCollection 2015 Feb.
• Bouzia A, Tassoudis V, Karanikolas M, Vretzakis G, Petsiti A, Tsilimingas N, Arnaoutoglou E. Pregabalin Effect on Acute and Chronic Pain after Cardiac Surgery. Anesthesiol Res Pract. 2017;2017:2753962. doi: 10.1155/2017/2753962. Epub 2017 Apr 30. Erratum In: Anesthesiol Res Pract. 2018 Oct 17;2018:5981895.
• Anwar S, Cooper J, Rahman J, Sharma C, Langford R. Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery. Anesthesiology. 2019 Jul;131(1):119-131. doi: 10.1097/ALN.0000000000002751.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2021
• Primary Completion (Actual): September 7, 2022
• Study Completion (Actual): September 7, 2022

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 7, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: OPIATE-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No