Effect of Parecoxib on Post-craniotomy Pain

Phase Four Study of Intravenous Parecoxib on Post-craniotomy Pain

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.

Study Overview

• Status: Completed
• Conditions: Anaesthesia
• Intervention / Treatment: Drug: Intravenous Parecoxib ('Dynastat' Pfizer)

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 Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Morphine consumption in 24 hour period.	24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Melbourne Health
• Investigators: Principal Investigator: Daryl L Williams, MBBS, Director of Anaesthesia, Royal Melbourne Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: April 1, 2007
• First Submitted That Met QC Criteria: April 2, 2007
• First Posted (Estimate): April 3, 2007

Study Record Updates

• Last Update Posted (Estimate): May 30, 2013
• Last Update Submitted That Met QC Criteria: May 28, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: pain; analgesia; neurosurgery; NSAIDS; morphine consumption; parecoxib
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Parecoxib
• Other Study ID Numbers: Parecoxib_HREC2006.133