Effects of Perioperative Pregabalin for Post-Craniotomy Pain

Effects of Perioperative Low-dose Pregabalin on Post-craniotomy Pain: A Two-centre Randomized Controlled Trial

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.

Study Overview

• Status: Withdrawn
• Conditions: Headache; Chronic Postoperative Pain
• Intervention / Treatment: Drug: Pregabalin; Drug: pregabalin; Drug: 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 Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Placebo	Drug: placebo; Identical placebo capsules will be administered in the same way.; Other Names: Identical placebo capsules
Experimental: Pregabalin 100 mg	Drug: Pregabalin; Pre-operatively, one of the 2 doses of pregabalin (100 or 150 mg) or placebo will be given to patients 1 hour before the surgery. Post-operatively, patients will receive daily (split in 2 equal doses) pregabalin 100 mg, pregabalin 150 mg, or placebo for the first 14 post-operative days.; Other Names: Lyrica
Experimental: pregabalin 150 mg	Drug: pregabalin; Pre-operatively, one of the 2 doses of pregabalin (100 or 150 mg) or placebo will be given to patients 1 hour before the surgery. Post-operatively, patients will receive daily (split in 2 equal doses) pregabalin 100 mg, pregabalin 150 mg, or placebo for the first 14 post-operative days.; Other Names: Lyrica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic post-craniotomy pain	The primary outcome of this study will be the incidence of chronic post-craniotomy pain at 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
length of hospital stay	30 days
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
post-operative pain scores at 48h	48 hours
incidence and severity of opioid-related side effects at day 2	Day 2
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

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Investigators: Principal Investigator: Andrea Rigamonti, MD, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: December 9, 2011
• First Submitted That Met QC Criteria: May 2, 2012
• First Posted (Estimate): May 4, 2012

Study Record Updates

• Last Update Posted (Estimate): February 19, 2014
• Last Update Submitted That Met QC Criteria: February 18, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: pregabalin; Craniotomy; post-craniotomy pain; chronic post-craniotomy headache
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Headache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: REB-10-388