Effects of Perioperative Pregabalin for Post-Craniotomy Pain

NCT ID: NCT01591980

Last Updated: 2014-02-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-08-31

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.

Conditions

Chronic Postoperative Pain; Headache

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pregabalin 100 mg

Group Type: EXPERIMENTAL

Pregabalin

Intervention Type: DRUG

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.

pregabalin 150 mg

Group Type: EXPERIMENTAL

pregabalin

Intervention Type: DRUG

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.

Placebo

Group Type: SHAM_COMPARATOR

placebo

Intervention Type: DRUG

Identical placebo capsules will be administered in the same way.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

placebo

Identical placebo capsules will be administered in the same way.

Intervention Type: DRUG

Other Intervention Names

Lyrica; Lyrica; Identical placebo capsules

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrea Rigamonti, MD

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Locations

St. Michael's Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

REB-10-388

Identifier Type: -

Identifier Source: org_study_id