Clinical trial NCT04517110: Perioperative Pregabalin for Reducing Opioid Consumption After Cardiac Surgery
Official title: Peri-Operative Pregabalin for Reducing opIoid Consumption AfTer Cardiac surgEry: A Randomized Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Opioid Use
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
Collaborators: name: McMaster University
First posted: 2020-08-18
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blinded randomized controlled trial
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cumulative opioid consumption
timeFrame: After surgery until discharge from hospital or 5 days, whichever is first.
measure: Daily opioid consumption
timeFrame: 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:
measure: Daily postoperative pain
timeFrame: Each postoperative day, beginning on postoperative day 1 and ending on the day of discharge from hospital or postoperative day 5, whichever is first.
measure: Average postoperative pain
timeFrame: Average of scores after surgery until discharge from hospital or 5 days, whichever is first.
measure: Cumulative consumption of antiemetic medications
timeFrame: After surgery until discharge from hospital or 5 days, whichever is first.
measure: Daily consumption of antiemetic medications
timeFrame: Each postoperative day, beginning on postoperative day 1 and ending on the day of discharge from hospital or postoperative day 5, whichever is first.
measure: Time to extubation
timeFrame: Within the first 5 days after surgery
measure: Mobility
timeFrame: Within the first 5 days after surgery
measure: Delirium
timeFrame: Starting the second day after surgery and ending after 5 days or 3 days of negative tests.
measure: Major adverse cardiovascular events
timeFrame: Within the first 5 days after surgery
measure: Death
timeFrame: Within the first 5 days after surgery
measure: Myocardial infarction
timeFrame: Within the first 5 days after surgery
measure: Stroke
timeFrame: Within the first 5 days after surgery
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Andre Lamy, MD, MHSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.
citation: 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.