Modulation of the Surgical Inflammatory Response by Etoricoxib

NCT00746720 | Terminated Phase 2 DMC

• 2 other identifiers: 02B2005EudraCT No.: 2005-003854-80
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain; Osteoarthritis, Hip; Postoperative Pain

Keywords

hip replacement; osteoarthritis; etoricoxib; pain; cerebrospinal fluid; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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.

  within 24 hours post dosing (study part 1) and within 48 hour post dosing (study part 2)

Secondary Outcomes (3)

• To determine the CSF (cerebrospinal fluid), plasma and tissue pharmacokinetics of orally administered etoricoxib.

  within 24 hours post dosing (study part 1) and within 48 hours post dosing (study part 2)

• To correlate the prostaglandin and cytokine response to clinical outcome parameters after hip arthroplasty.

  within 4 days post dosing (study part 1 and 2)

• 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.

  within 4 days post dosing (study part 1 and 2)

Study Arms (4)

A, 1

EXPERIMENTAL

Study part 1 (n = 8)

Drug: Etoricoxib 60 mg

A, 2

PLACEBO COMPARATOR

Study part 1 (n = 4)

Drug: Placebo for Etoricoxib 60 mg

B, 1

EXPERIMENTAL

Study part 2 (n = 20)

Drug: Etoricoxib 60 mg

B, 2

PLACEBO COMPARATOR

Study part 2 (n = 20)

Drug: Placebo for Etoricoxib 60 mg

Interventions

Etoricoxib 60 mg DRUG

film coated tablet 60 mg (orally), 120 mg (= 2 tablets a 60 mg) once daily, on day one post surgery

Also known as: Arcoxia 60 mg, MK0663

A, 1

Placebo for Etoricoxib 60 mg DRUG

film coated tablet (orally), two tablets once daily, on day one post surgery

Also known as: Matching Placebo

A, 2

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead
• HELIOS Kliniken GmbH: collaborator
• Rush University Medical Center: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

HELIOS Klinikum Berlin

Berlin, D-13125, Germany

Location

Related Publications (3)

• Buvanendran A, Kroin JS, Berger RA, Hallab NJ, Saha C, Negrescu C, Moric M, Caicedo MS, Tuman KJ. Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiology. 2006 Mar;104(3):403-10. doi: 10.1097/00000542-200603000-00005.

  PMID: 16508385 BACKGROUND

• Renner B, Zacher J, Buvanendran A, Walter G, Strauss J, Brune K. Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery--a pilot study. Naunyn Schmiedebergs Arch Pharmacol. 2010 Feb;381(2):127-36. doi: 10.1007/s00210-009-0482-0. Epub 2010 Jan 6.

  PMID: 20052461 RESULT

• Renner B, Walter G, Strauss J, Fromm MF, Zacher J, Brune K. Preoperative administration of etoricoxib in patients undergoing hip replacement causes inhibition of inflammatory mediators and pain relief. Eur J Pain. 2012 Jul;16(6):838-48. doi: 10.1002/j.1532-2149.2011.00062.x. Epub 2011 Dec 19.

  PMID: 22337568 RESULT

MeSH Terms

Conditions

Pain; Osteoarthritis, Hip; Pain, Postoperative; Osteoarthritis

Interventions

Etoricoxib

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Postoperative Complications; Pathologic Processes

Intervention Hierarchy (Ancestors)

Sulfones; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kay Brune, MD, PhD

  University of Erlangen-Nürnberg

  STUDY DIRECTOR

• Josef Zacher, MD, PhD

  Helios Klinikum Berlin-Buch

  PRINCIPAL INVESTIGATOR

• Martin Fromm, MD, PhD

  University of Erlangen-Nürnberg

  PRINCIPAL INVESTIGATOR

• Asokumar Buvanendran, MD

  Rush University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2008
• First Posted: September 4, 2008
• Study Start: May 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: December 1, 2010
• Last Updated: December 14, 2020

Record last verified: 2020-12

Locations

DE (1)