Perioperative Pregabalin for Reducing Opioid Consumption After Cardiac Surgery

NCT04517110 | Terminated Phase 3

• 1 other identifier: OPIATE-2020
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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).

Conditions

Opioid Use

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• 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.

• Average postoperative pain

  Average of scores after surgery until discharge from hospital or 5 days, whichever is first.

• Cumulative consumption of antiemetic medications

  After surgery until discharge from hospital or 5 days, whichever is first.

• 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.

• Time to extubation

  Within the first 5 days after surgery

Study Arms (2)

Pregabalin + Usual Care

EXPERIMENTAL

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; Drug: Pregabalin 75 mg; Other: Usual Care

Placebo + Usual Care

PLACEBO COMPARATOR

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; Drug: Pregabalin 75 mg Placebo; Other: Usual Care

Interventions

Pregabalin 300 mg DRUG

Pregabalin 300 mg, capsule

Also known as: Lyrica

Pregabalin + Usual Care

Pregabalin 75 mg DRUG

Pregabalin 75 mg twice daily, capsules

Also known as: Lyrica

Pregabalin + Usual Care

Pregabalin 300 mg Placebo DRUG

Placebo, matching Pregabalin 300 mg capsule

Also known as: Placebo Capsule

Placebo + Usual Care

Pregabalin 75 mg Placebo DRUG

Placebo, matching Pregabalin 75 mg capsules

Also known as: Placebo Capsule

Placebo + Usual Care

Usual Care OTHER

Usual Care

Placebo + Usual Care; Pregabalin + Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• Undergoing cardiac surgery with median sternotomy
• Provide written informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• McMaster University: collaborator

Study Sites (1)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (6)

• 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.

  PMID: 21474474 BACKGROUND

• 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.

  PMID: 23816671 BACKGROUND

• 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.

  PMID: 22234017 BACKGROUND

• 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.

  PMID: 25830118 BACKGROUND

• 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.

  PMID: 28539936 BACKGROUND

• 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.

  PMID: 31149930 BACKGROUND

MeSH Terms

Interventions

Pregabalin

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Andre Lamy, MD, MHSc

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matching placebo capsules
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiac Surgeon

Model Details: Double-blinded randomized controlled trial

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 18, 2020
• Study Start: April 9, 2021
• Primary Completion: September 7, 2022
• Study Completion: September 7, 2022
• Last Updated: September 10, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)