Effect of Parecoxib on Post-craniotomy Pain

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Melbourne Health
ClinicalTrials.gov Identifier:
NCT00455117
First received: April 1, 2007
Last updated: May 28, 2013
Last verified: May 2013
  Purpose

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 Intervention Phase
Anaesthesia
Drug: Intravenous Parecoxib ('Dynastat' Pfizer)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase Four Study of Intravenous Parecoxib on Post-craniotomy Pain

Resource links provided by NLM:


Further study details as provided by Melbourne Health:

Primary Outcome Measures:
  • Morphine consumption in 24 hour period. [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immediate post-operative hypertension (first 2 hours) [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Pain scores at zero (time of extubation), 1, 2, 4, 12, 24 hours post operatively [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Analgesic efficacy at 24 hours [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Incidence of post-operative nausea and vomiting (first 24 hours) [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Sedation or respiratory depression (first 24 hours) [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Safety Monitoring (Serious adverse side effects) [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Post-operative AMI [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Post-operative renal failure [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Post-operative thromboembolic stroke [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
  • Post-operative intracranial haemorrhage [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]

Enrollment: 130
Study Start Date: September 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00455117

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

No publications provided by Melbourne Health

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Melbourne Health
ClinicalTrials.gov Identifier: NCT00455117     History of Changes
Other Study ID Numbers: Parecoxib_HREC2006.133
Study First Received: April 1, 2007
Last Updated: May 28, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Melbourne Health:
analgesia
pain
neurosurgery
NSAIDS
parecoxib
morphine consumption

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

ClinicalTrials.gov processed this record on April 17, 2014