Perioperative Pregabalin for Reducing Opioid Consumption After Cardiac Surgery

Opioid Use Clinical Trial

— OPIATE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04517110
• Other study ID #: OPIATE-2020
• Status: Terminated
• Phase: Phase 3
• Start date: April 9, 2021
• Est. completion date: September 7, 2022

Study information

• Verified date: September 2022
• Source: Hamilton Health Sciences Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: September 7, 2022
• Est. primary completion date: September 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Opioid Use

Intervention

Drug:
• Pregabalin 300 mg
Pregabalin 300 mg, capsule
• Pregabalin 75 mg
Pregabalin 75 mg twice daily, capsules
• Pregabalin 300 mg Placebo
Placebo, matching Pregabalin 300 mg capsule
• Pregabalin 75 mg Placebo
Placebo, matching Pregabalin 75 mg capsules

Other:
• Usual Care
Usual Care

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative opioid consumption	Dose of opioids consumed (in morphine equivalents) by participants	After surgery until discharge from hospital or 5 days, whichever is first.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Time to extubation	Time from surgery completion until first successful extubation	Within the first 5 days after surgery
Secondary	Mobility	Proportion of mobility goals met after surgery	Within the first 5 days after surgery
Secondary	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.
Secondary	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
Secondary	Death	Number of participants experiencing death from any cause	Within the first 5 days after surgery
Secondary	Myocardial infarction	Number of participants experiencing myocardial infarction (MI) without death	Within the first 5 days after surgery
Secondary	Stroke	Number of participants experiencing stroke without death	Within the first 5 days after surgery