Clinical trial NCT00455117: Effect of Parecoxib on Post-craniotomy Pain
Official title: Phase Four Study of Intravenous Parecoxib on Post-craniotomy Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anaesthesia
Keywords: analgesia
pain
neurosurgery
NSAIDS
parecoxib
morphine consumption
Lead sponsor: Melbourne Health
Sponsor class: OTHER
First posted: 2007-04-03
Enrollment: 130
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: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Morphine consumption in 24 hour period.
timeFrame: 24 hours after surgery
Secondary outcomes:
measure: Immediate post-operative hypertension (first 2 hours)
timeFrame: 24 hours after surgery
measure: Pain scores at zero (time of extubation), 1, 2, 4, 12, 24 hours post operatively
timeFrame: 24 hours after surgery
measure: Analgesic efficacy at 24 hours
timeFrame: 24 hours after surgery
measure: Incidence of post-operative nausea and vomiting (first 24 hours)
timeFrame: 24 hours after surgery
measure: Sedation or respiratory depression (first 24 hours)
timeFrame: 24 hours after surgery
measure: Safety Monitoring (Serious adverse side effects)
timeFrame: 24 hours after surgery
measure: Post-operative AMI
timeFrame: 24 hours after surgery
measure: Post-operative renal failure
timeFrame: 24 hours after surgery
measure: Post-operative thromboembolic stroke
timeFrame: 24 hours after surgery
measure: Post-operative intracranial haemorrhage
timeFrame: 24 hours after surgery
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: Director of Anaesthesia, Royal Melbourne Hospital
name: Daryl L Williams, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Williams DL, Pemberton E, Leslie K. Effect of intravenous parecoxib on post-craniotomy pain. Br J Anaesth. 2011 Sep;107(3):398-403. doi: 10.1093/bja/aer223.