Etoricoxibe - Preemptive and Postoperative Analgesia for Abdominal and Thoracic Surgery

Pain Clinical Trial

— EPPA  

Official title:

Etoricoxibe - Preemptive and Postoperative Analgesia for Abdominal and Thoracic Surgery

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00716833
• Other study ID #: MPC-UM-0002-DI
• Status: Terminated
• Phase: Phase 3
• First received: July 15, 2008
• Last updated: January 15, 2015
• Start date: February 2006
• Est. completion date: December 2011

Study information

• Verified date: January 2015
• Source: Ludwig-Maximilians - University of Munich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesGermany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 87
• Est. completion date: December 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abdominal Surgery
• Pain
• Thoracic Surgery

Intervention

Drug:
• Etoricoxibe
Preemptive group patients get Etoricoxibe either twice (before and after surgery) or just a single preoperative dose.
• 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).

Locations

Country	Name	City	State
Germany	Zentrum für Pneumologie und Thoraxchirurgie, Asklepios Fachkliniken München-Gauting	Gauting
Germany	Chirurgische Klinik und Poliklinik, Innenstadt, Klinikum der Universität München	München

Sponsors (2)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Fleckenstein J, Kramer S, Offenbächer M, Schober G, Plischke H, Siebeck M, Mussack T, Hatz R, Lehmeyer L, Lang PM, Heindl B, Conzen P, Irnich D. Etoricoxib--preemptive and postoperative analgesia (EPPA) in patients with laparotomy or thoracotomy--design and protocols. Trials. 2010 May 27;11:66. doi: 10.1186/1745-6215-11-66. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative use of morphine as assessed within first 48 hours after surgery		first 48 hours	No
Secondary	Changes in patients level of sensibilisation will be measured with help of quantitative sensory testing (a standardised procedure) before and after surgery.		preoperative and 48h postoperative	No
Secondary	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.		48 hours postoperative	No