Clinical trial NCT01591980: Effects of Perioperative Pregabalin for Post-Craniotomy Pain
Official title: Effects of Perioperative Low-dose Pregabalin on Post-craniotomy Pain: A Two-centre Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Chronic Postoperative Pain
Headache
Keywords: post-craniotomy pain
pregabalin
chronic post-craniotomy headache
Craniotomy
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
First posted: 2012-05-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Chronic post-craniotomy pain
timeFrame: 3 months
Secondary outcomes:
measure: neuropathic component of the pain at 3 months
timeFrame: 3 months
measure: incidence of long-term pain at days 7
timeFrame: Day 7
measure: incidence of long-term pain at day 14
timeFrame: Day 14
measure: incidence of long-term pain at day 30
timeFrame: Day 30
measure: total opioid consumption in the first 24h
timeFrame: 24 hours
measure: total patient-controlled analgesia (PCA)demands and delivered doses in 24h
timeFrame: 24 hours
measure: post-operative pain scores at 24h
timeFrame: 24 hours
measure: post-operative pain scores at 48h
timeFrame: 48 hours
measure: incidence and severity of opioid-related side effects at day 2
timeFrame: Day 2
measure: incidence and severity of opioid-related side effects at Day 7
timeFrame: Day 7
measure: consumption of antiemetics in the first 24h
timeFrame: 24 hours
measure: tracheal extubation time
timeFrame: within 24 hours
measure: length of hospital stay
timeFrame: 30 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: Andrea Rigamonti, MD
role: PRINCIPAL_INVESTIGATOR
References: