Effect of Parecoxib on Post-craniotomy Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00455117
Recruitment Status : Completed
First Posted : April 3, 2007
Last Update Posted : May 30, 2013
Information provided by (Responsible Party):
Melbourne Health

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 Type : Interventional  (Clinical Trial)
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 : September 2006
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

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 Name: 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 Name: Intravenous parecoxib ("Dynastat" Pfizer)

Primary Outcome Measures :
  1. Morphine consumption in 24 hour period. [ Time Frame: 24 hours after surgery ]

Secondary Outcome Measures :
  1. Immediate post-operative hypertension (first 2 hours) [ Time Frame: 24 hours after surgery ]
  2. Pain scores at zero (time of extubation), 1, 2, 4, 12, 24 hours post operatively [ Time Frame: 24 hours after surgery ]
  3. Analgesic efficacy at 24 hours [ Time Frame: 24 hours after surgery ]
  4. Incidence of post-operative nausea and vomiting (first 24 hours) [ Time Frame: 24 hours after surgery ]
  5. Sedation or respiratory depression (first 24 hours) [ Time Frame: 24 hours after surgery ]
  6. Safety Monitoring (Serious adverse side effects) [ Time Frame: 24 hours after surgery ]
  7. Post-operative AMI [ Time Frame: 24 hours after surgery ]
  8. Post-operative renal failure [ Time Frame: 24 hours after surgery ]
  9. Post-operative thromboembolic stroke [ Time Frame: 24 hours after surgery ]
  10. Post-operative intracranial haemorrhage [ Time Frame: 24 hours after surgery ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00455117

Australia, Victoria
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3050
Sponsors and Collaborators
Melbourne Health
Principal Investigator: Daryl L Williams, MBBS Director of Anaesthesia, Royal Melbourne Hospital

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Melbourne Health Identifier: NCT00455117     History of Changes
Other Study ID Numbers: Parecoxib_HREC2006.133
First Posted: April 3, 2007    Key Record Dates
Last Update Posted: May 30, 2013
Last Verified: May 2013

Keywords provided by Melbourne Health:
morphine consumption

Additional relevant MeSH terms:
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents