Effects of Perioperative Pregabalin for Post-Craniotomy Pain

Phase 4

Withdrawn

• Conditions: Chronic Postoperative Pain; Headache
• Interventions: Drug: placebo; Drug: pregabalin

• Registration Number: NCT01591980
• Lead Sponsor: Unity Health Toronto

Brief Summary

Objective: To compare the incidence of chronic pain at 3 months among adults undergoing craniotomy between those received two different doses of pregabalin and those receiving placebo.

Detailed Description

Hypothesis: Perioperative pregabalin will reduce the incidence of chronic post-operative pain, and will reduce the opioid consumption, opioid-related side effects, and hospital length of stay compared with placebo in patients undergoing elective craniotomy.

Methods: 316 adults (18-65y), ASA I-III, undergoing elective craniotomy will be randomized to receive: 100mg or 150mg pregabalin or placebo once pre-operatively and 50mg or 75mg or placebo twice daily for 14 post-operative days. NRS pain scores, opioid consumption and side effects will be assessed up to 48h, and long-term pain at days 7, 14, 30, and 90. The primary analysis will involve the comparison between the 2 treatment groups together vs. placebo. A stepwise method will be used to evaluate the pairwise comparisons.

Outcomes: The primary outcome will be the incidence of chronic post-craniotomy pain at 3 mos. Important secondary outcomes are: neuropathic component of pain at 3 mos., total opioid consumption in the first 24h, and incidence and severity of opioid-related side effects at days 1, 2 and 7.

Study Timeline

• Study First Submitted: 2011-12-09
• Study First Submitted QC: 2012-05-02
• Study First Posted: 2012-05-04
• Study Start: 2013-08
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-18
• Last Update Posted: 2014-02-19
• Primary Completion: 2014-08
• Study Completion: 2014-08

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Adults, 18 to 65 years (limited to 65 years to lower the risk of over-sedation for elderly patients)
• Undergoing elective craniotomy (supratentorial or infratentorial) under general anaesthesia for: biopsy or resection of a tumour, clipping of an unruptured aneurysm, or excision of an arteriovenous malformation
• ASA physical status I-III

Exclusion Criteria

• predicted need for prolonged post-operative ventilation (> 12 hours)
• chronic pain secondary to previous craniotomy
• known adverse reaction to drugs used (gabapentin, pregabalin, hydromorphone, and/or acetaminophen)
• prior use of pregabalin or gabapentin (within 2 weeks before surgery)
• current history of moderate to severe headaches (NRS ≥ 4) related to intracranial pathology (tumour pain) since it may be difficult to discriminate between ongoing tumour pain and surgery-related post-operative pain
• current history of migraines
• pre-existing chronic pain requiring chronic opioid use (30mg morphine equivalent within 4 weeks of surgery)
• currently taking any drug that could interact with pregabalin
• current history of alcohol or recreational drug abuse
• known or suspected addiction to narcotic substances or chronic narcotic use in the last 2 weeks
• history of malignant hyperthermia (contraindicates the anaesthesia protocol of this study)
• history of angioedema
• Body Mass Index ≤ 18.4 or ≥ 35
• history of untreated obstructive sleep apnea
• any condition that would contraindicate the use of patient-controlled analgesia (PCA)
• lacks fluency in English
• pre-existing renal impairment (for pregabalin elimination)
• pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	-
Pregabalin 100 mg	pregabalin	-
pregabalin 150 mg	pregabalin	-

Primary Outcome Measures

Name	Time	Method
Chronic post-craniotomy pain	3 months	The primary outcome of this study will be the incidence of chronic post-craniotomy pain at 3 months

Secondary Outcome Measures

Name	Time	Method
length of hospital stay	30 days
post-operative pain scores at 48h	48 hours
incidence and severity of opioid-related side effects at day 2	Day 2
neuropathic component of the pain at 3 months	3 months
incidence of long-term pain at days 7	Day 7
incidence of long-term pain at day 14	Day 14
incidence of long-term pain at day 30	Day 30
total opioid consumption in the first 24h	24 hours
total patient-controlled analgesia (PCA)demands and delivered doses in 24h	24 hours
post-operative pain scores at 24h	24 hours
incidence and severity of opioid-related side effects at Day 7	Day 7
consumption of antiemetics in the first 24h	24 hours
tracheal extubation time	within 24 hours

Trial Locations

Locations (1)

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada