Effects of Perioperative Pregabalin for Post-Craniotomy Pain

Sponsor

Unity Health Toronto (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01591980

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Postoperative Pain Headache	Drug: Pregabalin Drug: pregabalin Drug: placebo	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2013

Anticipated Primary Completion Date :

Aug 1, 2014

Anticipated Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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
Sham Comparator: Placebo	Drug: placebo Identical placebo capsules will be administered in the same way. Other Names: Identical placebo capsules

Arm

Intervention/Treatment

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

Other Names:

Lyrica

Sham Comparator: Placebo

Drug: placebo

Identical placebo capsules will be administered in the same way.

Other Names:

Identical placebo capsules

Outcome Measures

Primary Outcome Measures

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

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]
length of hospital stay [30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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