Etoricoxibe - Preemptive and Postoperative Analgesia for Abdominal and Thoracic Surgery (EPPA)

This study has been terminated.
(poor recruitment)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Dominik Irnich, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT00716833
First received: July 15, 2008
Last updated: March 8, 2013
Last verified: March 2013
  Purpose

This randomised placebo controlled double-blinded bicentre study (phase III) was designed to evaluate the preemptive and postoperative analgetic impact of etoricoxibe in open abdominal and thoracic surgery. Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2).

Therefore 120 patients (ASA-risk 1-2) with upcoming abdominal or thoracic surgery should be included into this study. Patients are randomly allocated to either the preemptive or the postoperative Etoricoxibe group. These two groups are divided each into two arms. Preemptive group patients get Etoricoxibe either twice (before and after surgery) or just a single preoperative dose. Postoperative group patients get placebo before surgery and either a drug application or a placebo again after surgery (so called 2x2 factorial study design).

Cumulative use of morphine as assessed within first 48 hours after surgery is the primary trial outcome indicating the analgesic potency of Etoricoxibe.

In addition, changes in patients level of sensibilisation will be measured with help of quantitative sensory testing (a standardised procedure) before and after surgery (secondary outcome). In addition pharmacogenetic testing will provide information about genetic aberrations (so called polymorphisms) of the patients enzymes that should be compared to the individual reaction regarding Etoricoxibe.

The results will give hint about the analgesic impact of etoricoxibe in acute postoperative pain. There will be findings for preemptive analgesia and nerval processes. All this could lead to an improvement of postoperative pain relief while administrating preemptively a COX-2 selective inhibitor before surgery.


Condition Intervention Phase
Pain
Abdominal Surgery
Thoracic Surgery
Drug: Etoricoxibe
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Etoricoxibe - Preemptive and Postoperative Analgesia for Abdominal and Thoracic Surgery

Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • Cumulative use of morphine as assessed within first 48 hours after surgery [ Time Frame: first 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in patients level of sensibilisation will be measured with help of quantitative sensory testing (a standardised procedure) before and after surgery. [ Time Frame: preoperative and 48h postoperative ] [ Designated as safety issue: No ]
  • Pharmacogenetic testing will provide information about genetic aberrations (so called polymorphisms) of the patients enzymes that should be compared to the individual reaction regarding Etoricoxibe. [ Time Frame: 48 hours postoperative ] [ Designated as safety issue: No ]

Enrollment: 87
Study Start Date: February 2006
Study Completion Date: December 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Preemptive
Preemptive group patients get Etoricoxibe twice (before and after surgery) or just a single preoperative dose
Drug: Etoricoxibe
Preemptive group patients get Etoricoxibe either twice (before and after surgery) or just a single preoperative dose.
Other Name: Etoricoxibe 120mg Registration-N° 59863.02.00
Placebo Comparator: Postoperative
Postoperative group patients get placebo before surgery and either a drug application or a placebo again after surgery.
Drug: Placebo
Postoperative group patients get placebo before surgery and either a drug application or a placebo again after surgery (so called 2x2 factorial study design).
Other Name: Placebo-Etoricoxibe

Detailed Description:

Etoricoxib (brand name Arcoxia worldwide; also Algix and Tauxib in Italy) is a new COX-2 selective inhibitor (approx. 106.0 times more selective for COX-2 inhibition over COX-1). Doses are 120 mg/day for acute pain. Current therapeutic indications are: treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. Note that approved indications differ by country.

Like any other COX-2 selective inhibitor, Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2). This reduces the generation of prostaglandins (PGs) from arachidonic acid. Among the different functions exerted by PGs, their role in the inflammation cascade should be highlighted. COX-2 selective inhibitor (aka "COXIB") showed less marked activity on type 1 cycloxigenase compared to traditional non-steroidal anti-inflammatory drugs (NSAID). This reduced activity is the cause of reduced gastrointestinal toxicity.

Quantitative sensory tests (QST) are techniques employed to measure the intensity of stimuli needed to produce specific sensory perceptions. They are used to evaluate a sensory detection threshold or other sensory responses from supra-threshold stimulation. The common physical stimuli are (i) touch-pressure, (ii) vibration, and (iii) coolness, warmth, cold pain, and heat pain. In QST, the subject must be able to comprehend what is being asked by the test, alert and not taking mind-altering medications, and not biased to a certain test outcome.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Programmed abdominal or thoracic surgery
  • Patients > 18 yrs
  • Patients are aware of German language
  • Participation is voluntary
  • ASA-risk class 1-2 (American Society of Anesthesiologists guidelines)

Exclusion Criteria:

  • Severe cardiac, pulmonary, renal or neurologic disease
  • ASA risk III and IV
  • Insulin dependent Diabetes mellitus
  • Polyneuropathy
  • Chronic pain
  • Use of analgesic drugs
  • Ulcus duodeni
  • Ulcus ventriculi
  • Time after intestinal bleeding
  • Allergy reactions towards coxibes or coxibe-like drugs
  • Pregnancy and lactation
  • Severe hepatic disease (Albumin < 25 g/l or Child-Pugh-Score ≥ 10)
  • Children and Teenager < 16 years
  • Chronic intestinal inflammation
  • Heart failure (NYHA II - IV)
  • Inbalancend arterial hypertension
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00716833

Locations
Germany
Zentrum für Pneumologie und Thoraxchirurgie, Asklepios Fachkliniken München-Gauting
Gauting, Germany, 82131
Chirurgische Klinik und Poliklinik, Innenstadt, Klinikum der Universität München
München, Germany, 80336
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Dominik Irnich, PD. Dr. Multidisciplinary Pain Centre, Department of Anaesthesiology, University of Munich, Munich, Germany
  More Information

Publications:
Responsible Party: Dominik Irnich, PD Dr. Dominik Irnich, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT00716833     History of Changes
Other Study ID Numbers: MPC-UM-0002-DI
Study First Received: July 15, 2008
Last Updated: March 8, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission

Keywords provided by Ludwig-Maximilians - University of Munich:
pain
coxibe
preemptive
abdominothoracic
sensibilisation
Analgesia

ClinicalTrials.gov processed this record on July 24, 2014