Effects of Perioperative Pregabalin for Post-Craniotomy Pain

Unity Health Toronto

Status and phase

Withdrawn

Phase 4

Conditions

Chronic Postoperative Pain

Headache

Treatments

Drug: pregabalin

Drug: placebo

Drug: Pregabalin

Study type

Interventional

Funder types

Other

Identifiers

NCT01591980

REB-10-388

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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