Modulation of the Surgical Inflammatory Response by Etoricoxib

NCT ID: NCT00746720

Last Updated: 2020-12-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2010-12-31

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.

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.

Conditions

Pain; Osteoarthritis, Hip; Postoperative Pain

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

A, 1

Study part 1 (n = 8)

Group Type: EXPERIMENTAL

Etoricoxib 60 mg

Intervention Type: DRUG

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

A, 2

Study part 1 (n = 4)

Group Type: PLACEBO_COMPARATOR

Placebo for Etoricoxib 60 mg

Intervention Type: DRUG

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

B, 1

Study part 2 (n = 20)

Group Type: EXPERIMENTAL

Etoricoxib 60 mg

Intervention Type: DRUG

film coated tablet (orally), 120 mg (= 2 tablets a 60 mg) once daily, two hours before and 24 hours after surgery

B, 2

Study part 2 (n = 20)

Group Type: PLACEBO_COMPARATOR

Placebo for Etoricoxib 60 mg

Intervention Type: DRUG

film coated tablet (orally), 2 tablets once daily, two hours before and 24 hours after surgery

Interventions

Etoricoxib 60 mg

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

Intervention Type: DRUG

Placebo for Etoricoxib 60 mg

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

Intervention Type: 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

Intervention Type: DRUG

Placebo for Etoricoxib 60 mg

film coated tablet (orally), 2 tablets once daily, two hours before and 24 hours after surgery

Intervention Type: DRUG

Other Intervention Names

Arcoxia 60 mg; MK0663; Matching Placebo; Arcoxia 60 mg; MK0663; Matching Placebo

Eligibility 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

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HELIOS Kliniken GmbH

UNKNOWN

Sponsor Role: collaborator

Rush University Medical Center

OTHER

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kay Brune, MD, PhD

Role: STUDY_DIRECTOR

University of Erlangen-Nürnberg

Josef Zacher, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Helios Klinikum Berlin-Buch

Martin Fromm, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Erlangen-Nürnberg

Asokumar Buvanendran, MD

Role: PRINCIPAL_INVESTIGATOR

Rush University

Locations

HELIOS Klinikum Berlin

Berlin, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 16508385 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20052461 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22337568 (View on PubMed)

Other Identifiers

EudraCT No.: 2005-003854-80

Identifier Type: -

Identifier Source: secondary_id

02B2005

Identifier Type: -

Identifier Source: org_study_id