Modulation of the Surgical Inflammatory Response by Etoricoxib

This study has been terminated.
(Patient recruitment difficulties)
Sponsor:
Collaborators:
HELIOS Kliniken GmbH
Rush University Medical Center
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT00746720
First received: September 3, 2008
Last updated: May 2, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to test the hypothesis that orally administered etoricoxib (COX-2) modulates prostaglandin and cytokine synthesis in the central nervous system (CNS) and in the periphery in surgical patients and thus reduces pain and suffering.


Condition Intervention Phase
Pain
Osteoarthritis, Hip
Postoperative Pain
Drug: Etoricoxib 60 mg
Drug: Placebo for Etoricoxib 60 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Modulation of the Surgical Inflammatory Response by Etoricoxib: Peripheral Versus Central

Resource links provided by NLM:


Further study details as provided by University of Erlangen-Nürnberg Medical School:

Primary Outcome Measures:
  • To test the hypothesis that orally administered etoricoxib (COX-2 inhibitor) modulates prostaglandin and cytokine synthesis in the central nervous system (CNS) and in the periphery in surgical patients. [ Time Frame: within 24 hours post dosing (study part 1) and within 48 hour post dosing (study part 2) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the CSF (cerebrospinal fluid), plasma and tissue pharmacokinetics of orally administered etoricoxib. [ Time Frame: within 24 hours post dosing (study part 1) and within 48 hours post dosing (study part 2) ] [ Designated as safety issue: No ]
  • To correlate the prostaglandin and cytokine response to clinical outcome parameters after hip arthroplasty. [ Time Frame: within 4 days post dosing (study part 1 and 2) ] [ Designated as safety issue: Yes ]
  • To assess the safety (via clinical laboratory tests and adverse events) of a single dose of 120 mg Etoricoxib for one day (Part1) or for two days (Part2) and placebo. [ Time Frame: within 4 days post dosing (study part 1 and 2) ] [ Designated as safety issue: Yes ]

Enrollment: 23
Study Start Date: May 2006
Study Completion Date: December 2010
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A, 1
Study part 1 (n = 8)
Drug: Etoricoxib 60 mg
film coated tablet 60 mg (orally), 120 mg (= 2 tablets a 60 mg) once daily, on day one post surgery
Other Names:
  • Arcoxia 60 mg
  • MK0663
Placebo Comparator: A, 2
Study part 1 (n = 4)
Drug: Placebo for Etoricoxib 60 mg
film coated tablet (orally), two tablets once daily, on day one post surgery
Other Name: Matching Placebo
Experimental: B, 1
Study part 2 (n = 20)
Drug: Etoricoxib 60 mg
film coated tablet (orally), 120 mg (= 2 tablets a 60 mg) once daily, two hours before and 24 hours after surgery
Other Names:
  • Arcoxia 60 mg
  • MK0663
Placebo Comparator: B, 2
Study part 2 (n = 20)
Drug: Placebo for Etoricoxib 60 mg
film coated tablet (orally), 2 tablets once daily, two hours before and 24 hours after surgery
Other Name: Matching Placebo

Detailed Description:

This study will be a multiple centre, double-blind, placebo-controlled, randomized, parallel group study conducted in male and female adult patients undergoing elective primary single hip arthroplasty. In part 1 of the study 12 patients will be enrolled in the study and will be administrated 120 mg Etoricoxib or placebo orally on day one post surgery. The results from part 1 should help to adjust sampling time points (for blood, cerebrospinal fluid and hip drain fluid) if necessary. In part 2 of the study 40 patients will be enrolled and should receive 120 mg etoricoxib or placebo two hours before and 24 hours after surgery.

Primary end points will be the inflammatory mediators on peripheral and central levels. After surgical manipulation we expect increased mediators on both sides. It will be investigated if the medication could reduce the mediators compared to placebo and if the effect is related to pharmacokinetic parameters.

  Eligibility

Ages Eligible for Study:   55 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject undergoing elective primary single hip arthroplasty
  • Subject diagnosed with Osteoarthritis / arthrosis
  • Subject has not taken non-steroidal anti-inflammatory drugs within 4 of their terminal half life times prior to enrollment
  • Subject capable of understanding and cooperating with the requirements of the study

Exclusion Criteria:

  • Patients with renal insufficiency (serum creatinine >1.5 mg/dl)
  • Recent major trauma or systemic infection (within 3 months)
  • Use of corticosteroid medication or chronic opioids (within 3 months)
  • Any other condition likely to affect prostaglandin and cytokine levels
  • Participation in another clinical study or receipt of an investigational drug within 30 days
  • Hypersensitivity to any component of the etoricoxib and/or placebo tablets
  • Uncontrolled hypertension defined as systolic blood pressure >140 mm Hg and diastolic pressure >90 mm Hg at rest after two repeated measurements
  • Congestive heart failure (NYHA II-IV)
  • Cerebrovascular disease
  • Established ischemic heart disease (including patients who have recently undergone coronary artery bypass graft surgery or angioplasty)
  • Patients with any kind or severity of cirrhosis of the liver or cholestasis or elevated liver function enzymes (ALT or AST 3 fold) as a sign of clinical significant liver malfunction (corresponds to any Child-Pugh-Score ≥5)
  • Patients who have developed signs of asthma, acute rhinitis, nasal polyps, angioneurotic oedema or urticaria following the administration of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs)
  • Pregnancy and lactation
  • Patients with active peptic ulcerations or active gastro-intestinal (GI) bleeding
  • Inflammatory bowel disease
  • Recent history (within the last year) of alcohol or other substance abuse
  • An employee of the sponsor or study site
  • Any neurological syndrome or any other condition leading to contra-indication to spinal anesthesia
  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: NCT00746720

Locations
Germany
HELIOS Klinikum Berlin
Berlin, Germany, D-13125
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
HELIOS Kliniken GmbH
Rush University Medical Center
Merck Sharp & Dohme Corp.
Investigators
Study Director: Kay Brune, MD, PhD University of Erlangen-Nürnberg
Principal Investigator: Josef Zacher, MD, PhD HELIOS Klinikum Berlin
Principal Investigator: Martin Fromm, MD, PhD University of Erlangen-Nürnberg
Principal Investigator: Asokumar Buvanendran, MD Rush University
  More Information

Publications:
Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT00746720     History of Changes
Other Study ID Numbers: 02B2005, EudraCT No.: 2005-003854-80
Study First Received: September 3, 2008
Last Updated: May 2, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
European Union: European Medicines Agency

Keywords provided by University of Erlangen-Nürnberg Medical School:
hip replacement
osteoarthritis
etoricoxib
pain
cerebrospinal fluid
pharmacokinetics

Additional relevant MeSH terms:
Osteoarthritis
Pain, Postoperative
Osteoarthritis, Hip
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Etoricoxib
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
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 16, 2014