Effect of Parecoxib on Post-craniotomy Pain

Sponsor

Melbourne Health (Other)

Overall Status

Completed

CT.gov ID

NCT00455117

Collaborator

(none)

130

Enrollment

Location

Arms

Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Aim of this trial:

To investigate whether post-craniotomy analgesia with (i) intravenous (IV) parecoxib plus intravenous paracetamol is superior to (ii) intravenous paracetamol alone.

Study Hypothesis:

Post-operative analgesia with intravenous parecoxib in combination with intravenous paracetamol will be superior to intravenous paracetamol alone.

Condition or Disease	Intervention/Treatment	Phase
Anaesthesia	Drug: Intravenous Parecoxib ('Dynastat' Pfizer)	Phase 4

Detailed Description

Neurosurgical patients undergoing brain procedures (craniotomy patients) are known to suffer moderately severe postoperative pain and high rates of post-operative nausea and vomiting. Post-craniotomy pain is poorly treated with more than 50% of craniotomy patients experiencing postoperative pain of moderate or severe intensity. Fear of drug complications such as sedation, respiratory depression, seizures and intracranial bleeding has inhibited prescribing of effective pain treatment.Non-steroidal anti-inflammatory drugs (NSAIDS) are known to be effective analgesics in the peri-operative period however there use in cranial neurosurgery has been limited due to risk of bleeding. Parecoxib is an injectable form of NSAID that works through inhibiting cyclo-oxygenase type-2 (COX-2). The main benefit of COX-2 inhibitors is that they have minimal inhibition of platelet function and therefore minimal risk of increased bleeding.This project aims to evaluate whether parecoxib is an effective pain reliever (analgesic) after brain surgery. Patients aged 18-65 years presenting for elective craniotomy will be randomly allocated to two different analgesic programs (i) IV parecoxib and IV paracetamol or (ii) IV paracetamol. All patients will receive a standardised anaesthetic. Scalp infiltration, using 20mls of local anesthetic (bupivacaine 0.5% with adrenaline), will occur prior to skin incision. Intermittent morphine administration will used post-operatively to ensure adequate analgesia in each arm of the trial. Immediate post-operative adjunctive analgesia will be provided with nurse administered IV morphine in the post-anaesthetic care unit (PACU) as per protocol (RMH protocol for opioid titration), followed by patient controlled analgesia (PCA) morphine once the verbal rating scale is < 4 (rating out of ten). A score of less than four is considered to be mild pain. PCA will be continued for the first twenty-four hours then discontinued. Patients will then receive strict oral paracetamol and nurse administered IV morphine as required. The primary study endpoint will be morphine consumption in the first 24 hours. Data will be analysed on an intention to treat basis. Continuous variables will be graphed to determine their distribution. Normally distributed variables will be described using mean and standard deviation and compared using Student's t-tests. Skewed variables will be described using median and range (or interquartile range) and compared using Wilcoxon rank sum tests. A p-value les than 0.05 will be considered statistically significant.

Study Design

Study Type:

Interventional

Actual Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Phase Four Study of Intravenous Parecoxib on Post-craniotomy Pain

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 placebo (2 ml normal saline) administered intravenously at dural closure during craniotomy	Drug: Intravenous Parecoxib ('Dynastat' Pfizer) parecoxib or placebo Other Names: Intravenous parecoxib ("Dynastat" Pfizer)
Active Comparator: 2 parecoxib 40 mg in 2 ml normal saline administered intravenously at dural closure during craniotomy	Drug: Intravenous Parecoxib ('Dynastat' Pfizer) parecoxib or placebo Other Names: Intravenous parecoxib ("Dynastat" Pfizer)

Arm

Intervention/Treatment

Placebo Comparator: 1

placebo (2 ml normal saline) administered intravenously at dural closure during craniotomy

Drug: Intravenous Parecoxib ('Dynastat' Pfizer)

parecoxib or placebo

Other Names:

Intravenous parecoxib ("Dynastat" Pfizer)

Active Comparator: 2

parecoxib 40 mg in 2 ml normal saline administered intravenously at dural closure during craniotomy

Drug: Intravenous Parecoxib ('Dynastat' Pfizer)

parecoxib or placebo

Other Names:

Intravenous parecoxib ("Dynastat" Pfizer)

Outcome Measures

Primary Outcome Measures

Morphine consumption in 24 hour period. [24 hours after surgery]

Secondary Outcome Measures

Immediate post-operative hypertension (first 2 hours) [24 hours after surgery]
Pain scores at zero (time of extubation), 1, 2, 4, 12, 24 hours post operatively [24 hours after surgery]
Analgesic efficacy at 24 hours [24 hours after surgery]
Incidence of post-operative nausea and vomiting (first 24 hours) [24 hours after surgery]
Sedation or respiratory depression (first 24 hours) [24 hours after surgery]
Safety Monitoring (Serious adverse side effects) [24 hours after surgery]
Post-operative AMI [24 hours after surgery]
Post-operative renal failure [24 hours after surgery]
Post-operative thromboembolic stroke [24 hours after surgery]
Post-operative intracranial haemorrhage [24 hours after surgery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Supratentorial craniotomy, glasgow coma scale 15

Exclusion Criteria:

Chronic pain,
Chronic opioid use.
History of significant alcohol or benzodiazepine (BZD) use,
Inability to speak English,
Pre-operative aphasia or dysphasia,
Renal impairment (Creatinine level > 0.1),
Asthma (or evidence of reversible airway obstruction,
Known ischaemic heart disease or cerebrovascular disease,
American Society of Anaesthesiologists (ASA) grade IV or V,
Allergy to any study drug (paracetamol, parecoxib, sulphas, morphine, bupivacaine, propofol, remifentanil;
Administration of oral paracetamol within previous 8 hours.
Pregnancy or breastfeeding