Assessment of the Response to Etoricoxib in Patients With Ankylosing Spondylitis and Inadequate Response to ≥2 NSAIDs

NCT ID: NCT01091675

Last Updated: 2015-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2013-05-31

Brief Summary

The goal of this research is to assess the percentage of non-responders to ≥ 2 NSAIDs candidates a biological therapy that could adequately respond to treatment with etoricoxib This study confirm the result of a previous study in a wider similar population. Basing on previous results, the response rate will be assessed by ASASBIO criteria. The efficacy of the treatment with etoricoxib 90 mg will be assessed at week 4 in a population of patients with AS who didn't respond adequately to a previous therapy with ≥ 2 NSAIDs.

Those patients that, based on the ASABIO criteria, achieved a sufficient clinical response will be followed until week 24 to asses the maintenance of the study drug effects.

Detailed Description

Etoricoxib is an oral, selective cyclooxygenase 2 inhibitor approved for the symptomatic treatment of ankylosing spondylitis (AS) in Spain.

Etoricoxib is a marketed product indicated for the relief of symptomatic osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain and signs of inflammation associated with acute gouty arthritis. In ankylosing spondylitis,the recommended dose is 90 mg once daily.

Clinical pharmacology studies demonstrate that Etoricoxib induce dose-dependent inhibition of COX-2 without inhibit COX-1, up to 150 mg daily dose.

Etoricoxib did not inhibit the gastric synthesis of prostaglandin and had no effect on platelet function. Cyclooxygenase is responsible for the prostaglandin synthesis. Were identified two different isoforms of cyclooxygenase, COX-1 and COX-2. It has been shown that COX-2 is the major enzyme responsible for the synthesis of prostanoid mediators involved in pain, inflammation and fever.

Conditions

Ankylosing Spondylitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

etoricoxib

All the patients who fulfil the eligibility criteria will start a 4-week open label treatment period to evaluate the response to treatment with etoricoxib 90 mg.

Group Type: EXPERIMENTAL

Etoricoxib

Intervention Type: DRUG

Etoricoxib 90 mg/day/PO during 4 weeks Positive response to the therapy (in investigator opinion): Ongoing treatment with 90 mg/day/PO until 24 weeks.

Interventions

Etoricoxib

Etoricoxib 90 mg/day/PO during 4 weeks Positive response to the therapy (in investigator opinion): Ongoing treatment with 90 mg/day/PO until 24 weeks.

Intervention Type: DRUG

Other Intervention Names

Arcoxia

Eligibility Criteria

Inclusion Criteria

1. Patients ≥ 18 years.

2. Patients with diagnosis of AS (based on New York criteria) made ≥ 6 months prior to study start.

3. Patient with axial involvement.

4. Patients who have been treated with ≥ 2 documented NSAID with proven anti-inflammatory potency during at least 3 months at maximal recommended or tolerated doses prior the visit 1.

5. Patients who demonstrate a Bath Ankylosing Spondylitis Disease Activity Index score of ≥ 4 (range 0-10).

Exclusion Criteria

1. Patient that according to the investigator opinion is legally unable (i.e. mentally incapable person), with psychiatric disorder precedent, active psychosis or emotional problems at the moment to be enrolled in the study.

2. Patient who is participating in a clinical study with a drug or experimental device or it was done within 4 weeks prior to the inform consent signature.

3. Patient with a recent history (since last 5 years) of abuse or dependence to opiates, tranquilizer or drugs at the inform consent signature moment. Patient with a recent history (since last 5 years) of alcoholism or drug addiction.

4. Patient with a history of neoplastic disease or malignant neoplasia ≤ 5 years prior to the inform consent signature, except basal cell or squamous cell cancer skin adequately treated or uterine cancer insitu without recurrence prior to study entry according to the investigator opinion. Patients with history of leukemia, lymphoma, malignant melanoma or myeloproliferative disease cannot participate at the study.

5. Pregnancy, lactation or waiting to conceive a child

6. Patient with history of disorders, treatments or laboratory abnormality that can interfere with the study results and study participation.

7. Patient cannot comply with the study procedures, study calendar. Patient with plan of moving.

8. Patients awaiting the legal assessment of the degree of disability or the permanent work disability

9. Patients unable to respond to questionnaires (difficulty understanding and / or reading of questionnaires)

10. Any other warning that, in the investigator opinion, could discourage the inclusion of the patient in the study.

11. Patient to be treated with other drug which can modulate the pain perception

12. Patients with AS associated disease (inflammatory bowel disease, psoriasis).

13. Patients with active peripheral articular involvement defined by presence of peripheral arthritis.

14. Patient with predominant enthesitis or an enthesis that, according to investigator's opinion, can confound the correct evaluation.

15. Presence of extra-articular manifestations.

16. Patients with fibromyalgia or other rheumatic disorders that could confound the evaluation of efficacy

17. Patients with AS who received biologic therapy. Note: The use of approved nonstudy antirheumatic therapy at a stable dose(methotrexate, sulfasalazine) for 3 months prior to the study start will be allowed.

18. Patients with AS who received active treatment with etoricoxib

19. Hypersensitivity to the active substance or to any of the excipients

20. Active peptic ulceration or active gastro-intestinal bleeding

21. Patients with severe renal failure (creatinine clearance rate < 30 ml/min)

22. Congestive heart failure (NYHA II-IV)

23. Established ischaemic heart disease or cerebrovascular disease

24. Patients with severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10).

25. Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetylsalicylic acid or NSAIDs including cyclooxygenase-2 inhibitors

26. Patients with hypertension whose blood pressure is persistently elevated above 140/90mmHg and has not been adequately controlled

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• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spanish Foundation of Rheumatology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jordi Gratacós, PhD/ MD

Role: PRINCIPAL_INVESTIGATOR

Parc Tauli Hospital

Eduardo Collantes Estevez, PhD/ MD

Role: PRINCIPAL_INVESTIGATOR

Reina Sofia Hospital

Xavier Juanola Roura, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Bellvitge Hospital

Raimon Sanmartí Sala, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic i Provincial Barcelona

Juan Mulero Mendoza, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Puerta de Hierro Hospital

Estefania Moreno Ruzafa, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

San Rafael Hospital

Luis Francisco Linares Ferrando, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Virgen de la Arrixaca Hospital

Rubén Queiro Silva, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Asturias Hospital

Elia Brito Brito, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Ramon y Cajal Hospital

Carlos Alberto Montilla Morales, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Salamanca

Maria Cruces Fernández Espartero, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

General de Mostoles Hospital

Pilar Fernández Dapica, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital 12 de Octubre

Rosario García de Vicuña, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital de la Princesa

Rosa Morlá, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Sant Pau i Santa Tecla Hospital

Locations

Sant Rafael Hospital

Barcelona, Barcelona, Spain

Clinic I Provincial Hospital

Barcelona, Barcelona, Spain

Bellvitge Hospital

Barcelona, Barcelona, Spain

Parc Tauli Hospital

Sabadell, Barcelona, Spain

Reina Sofia University Hospital

Córdoba, Cordoba, Spain

Ramon Y Cajal Hospital

Madrid, Madrid, Spain

University Hospital 12 Octubre

Madrid, Madrid, Spain

Puerta de Hierro Hospital

Madrid, Madrid, Spain

Hospital General of Mostoles

Madrid, Madrid, Spain

Virgen de la Arrixaca Hospital

Murcia, Murcia, Spain

Central Hospital of Asturias

Oviedo, Principality of Asturias, Spain

Hospital Clinic of Salamanca

Salamanca, Salamanca, Spain

University Hospital de la Princesa

Madrid, , Spain

Sant Pau i Santa Tecla Hospital

Tarragona, , Spain

Countries

Spain

References

Estévez, E. Collantes, and A. Escudero Contreras.

Reference Type: BACKGROUND

Sociedad Española de reumatología: estudio EPISER. Prevalencia de las enfermedades reumáticas en la población española. Reumatología. Madrid, Merck, Sharp & Dohme, 2001.

Reference Type: BACKGROUND

van der Heijde D, Baraf HS, Ramos-Remus C, Calin A, Weaver AL, Schiff M, James M, Markind JE, Reicin AS, Melian A, Dougados M. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study. Arthritis Rheum. 2005 Apr;52(4):1205-15. doi: 10.1002/art.20985.

Reference Type: BACKGROUND

PMID: 15818702 (View on PubMed)

Jarrett SJ, Sivera F, Cawkwell LS, Marzo-Ortega H, McGonagle D, Hensor E, Coates L, O'Connor PJ, Fraser A, Conaghan PG, Emery P. MRI and clinical findings in patients with ankylosing spondylitis eligible for anti-tumour necrosis factor therapy after a short course of etoricoxib. Ann Rheum Dis. 2009 Sep;68(9):1466-9. doi: 10.1136/ard.2008.092213. Epub 2008 Oct 24.

Reference Type: BACKGROUND

PMID: 18952641 (View on PubMed)

Braun J, Pham T, Sieper J, Davis J, van der Linden S, Dougados M, van der Heijde D; ASAS Working Group. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2003 Sep;62(9):817-24. doi: 10.1136/ard.62.9.817.

Reference Type: BACKGROUND

PMID: 12922952 (View on PubMed)

Other Identifiers

2009-017309-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GRE-2009-01

Identifier Type: -

Identifier Source: org_study_id