Back to results

Modulation of the Surgical Inflammatory Response by Etoricoxib

Primary Purpose

Pain, Osteoarthritis, Hip, Postoperative Pain

Status

Terminated

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Etoricoxib 60 mg

Placebo for Etoricoxib 60 mg

Etoricoxib 60 mg

Placebo for Etoricoxib 60 mg

About this trial

This is an interventional treatment trial for Pain focused on measuring hip replacement, osteoarthritis, etoricoxib, pain, cerebrospinal fluid, pharmacokinetics

Eligibility Criteria

55 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

HELIOS Klinikum Berlin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

A, 1

A, 2

B, 1

B, 2

Arm Description

Study part 1 (n = 8)

Study part 1 (n = 4)

Study part 2 (n = 20)

Outcomes

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.

Secondary Outcome Measures

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

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

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.

Full Information

NCT ID

NCT00746720

First Posted

September 3, 2008

Last Updated

December 10, 2020

Sponsor

University of Erlangen-Nürnberg Medical School

Collaborators

HELIOS Kliniken GmbH, Rush University Medical Center, Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT00746720

Brief Title

Modulation of the Surgical Inflammatory Response by Etoricoxib

Official Title

Modulation of the Surgical Inflammatory Response by Etoricoxib: Peripheral Versus Central

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Terminated

Why Stopped

Patient recruitment difficulties

Study Start Date

May 2006 (undefined)

Primary Completion Date

July 2009 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Erlangen-Nürnberg Medical School

Collaborators

HELIOS Kliniken GmbH, Rush University Medical Center, Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pain, Osteoarthritis, Hip, Postoperative Pain

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A, 1

Arm Type

Experimental

Arm Description

Study part 1 (n = 8)

Arm Title

A, 2

Arm Type

Placebo Comparator

Arm Description

Study part 1 (n = 4)

Arm Title

B, 1

Arm Type

Experimental

Arm Description

Study part 2 (n = 20)

Arm Title

B, 2

Arm Type

Placebo Comparator

Arm Description

Study part 2 (n = 20)

Intervention Type

Drug

Intervention Name(s)

Etoricoxib 60 mg

Other Intervention Name(s)

Arcoxia 60 mg, MK0663

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo for Etoricoxib 60 mg

Other Intervention Name(s)

Matching Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Etoricoxib 60 mg

Other Intervention Name(s)

Arcoxia 60 mg, MK0663

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo for Etoricoxib 60 mg

Other Intervention Name(s)

Matching Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Time Frame

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

Secondary Outcome Measure Information:

Title

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)

Title

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)

Title

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kay Brune, MD, PhD

Organizational Affiliation

University of Erlangen-Nürnberg

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Josef Zacher, MD, PhD

Organizational Affiliation

Helios Klinikum Berlin-Buch

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Martin Fromm, MD, PhD

Organizational Affiliation

University of Erlangen-Nürnberg

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Asokumar Buvanendran, MD

Organizational Affiliation

Rush University

Official's Role

Principal Investigator

Facility Information:

Facility Name

HELIOS Klinikum Berlin

City

Berlin

ZIP/Postal Code

D-13125

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

16508385

Citation

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. Erratum In: Anesthesiology. 2006 Apr;104(4):900.

Results Reference

background

PubMed Identifier

20052461

Citation

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.

Results Reference

result

PubMed Identifier

22337568

Citation

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.

Results Reference

result

Learn more about this trial

Modulation of the Surgical Inflammatory Response by Etoricoxib

We'll reach out to this number within 24 hrs