OPIATE: Perioperative Pregabalin for Reducing Opioid Consumption After Cardiac Surgery

• Sponsor: Hamilton Health Sciences Corporation (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04517110
• Collaborator: McMaster University (Other)
• Enrollment: 200
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 18
• Patients Per Site Per Month: 11.1

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Opioid Use	Drug: Pregabalin 300 mg; Drug: Pregabalin 75 mg; Drug: Pregabalin 300 mg Placebo; Drug: Pregabalin 75 mg Placebo; Other: Usual Care	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double-blinded randomized controlled trialDouble-blinded randomized controlled trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Matching placebo capsules
• Primary Purpose: Treatment
• Official Title: Peri-Operative Pregabalin for Reducing opIoid Consumption AfTer Cardiac surgEry: A Randomized Trial
• Actual Study Start Date: Apr 9, 2021
• Anticipated Primary Completion Date: Oct 9, 2022
• Anticipated Study Completion Date: Oct 9, 2022

Arms and Interventions

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.	Drug: Pregabalin 300 mg; Pregabalin 300 mg, capsule; Other Names: Lyrica ; Drug: Pregabalin 75 mg; Pregabalin 75 mg twice daily, capsules; Other Names: Lyrica ; Other: Usual Care; Usual Care
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.	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 ; Other: Usual Care; Usual Care

Outcome Measures

Primary Outcome Measures

1. Cumulative opioid consumption [After surgery until discharge from hospital or 5 days, whichever is first.]

   Dose of opioids consumed (in morphine equivalents) by participants

2. Daily opioid consumption [Each postoperative day, beginning on postoperative day 1 and ending on the day of discharge from hospital or postoperative day 5, whichever is first.]

   Dose of opioids consumed (in morphine equivalents) by participants

Secondary Outcome Measures

1. Daily postoperative pain [Each postoperative day, beginning on postoperative day 1 and ending on the day of discharge from hospital or postoperative day 5, whichever is first.]

   Acute postoperative pain assessed by the numeric rating scale (NRS; 0 to 10)

2. Average postoperative pain [Average of scores after surgery until discharge from hospital or 5 days, whichever is first.]

   Acute postoperative pain assessed by the numeric rating scale (NRS; 0 to 10)

3. Cumulative consumption of antiemetic medications [After surgery until discharge from hospital or 5 days, whichever is first.]

   Dose of gravol or ondansetron consumed by participants

4. Daily consumption of antiemetic medications [Each postoperative day, beginning on postoperative day 1 and ending on the day of discharge from hospital or postoperative day 5, whichever is first.]

   Dose of gravol or ondansetron consumed by participants

5. Time to extubation [Within the first 5 days after surgery]

   Time from surgery completion until first successful extubation

6. Mobility [Within the first 5 days after surgery]

   Proportion of mobility goals met after surgery

7. Delirium [Starting the second day after surgery and ending after 5 days or 3 days of negative tests.]

   Number of participants meeting the Confusion Assessment Method (CAM) criteria

8. Major adverse cardiovascular events [Within the first 5 days after surgery]

   The first occurrence of death, non-fatal myocardial infarction (MI) or non-fatal stroke

9. Death [Within the first 5 days after surgery]

   Number of participants experiencing death from any cause

10. Myocardial infarction [Within the first 5 days after surgery]

    Number of participants experiencing myocardial infarction (MI) without death

11. Stroke [Within the first 5 days after surgery]

    Number of participants experiencing stroke without death

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hamilton General Hospital	Hamilton	Ontario	Canada	L8L 2X2

Sponsors and Collaborators

• Hamilton Health Sciences Corporation
• McMaster University

Investigators

• Principal Investigator: Andre Lamy, MD, MHSc, Hamilton Health Sciences Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• Pesonen A, Suojaranta-Ylinen R, Hammarén 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.
• 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.

• Responsible Party: Andre Lamy, Cardiac Surgeon, Hamilton Health Sciences Corporation
• ClinicalTrials.gov Identifier: NCT04517110
• Other Study ID Numbers: OPIATE-2020
• First Posted: Aug 18, 2020
• Last Update Posted: May 24, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Pregabalin

Study Results

No Results Posted as of May 24, 2021