Clinical trial NCT01091675: Assessment of the Response to Etoricoxib in Patients With Ankylosing Spondylitis and Inadequate Response to ≥2 NSAIDs
Official title: Assessment of the Response to Etoricoxib in Patients With Ankylosing Spondylitis (AS) and Inadequate Response to ≥2 Nonsteroidal Antiinflammatory Drug (NSAID)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ankylosing Spondylitis
Keywords: ankylosing spondylitis
biologic therapies
ASAS
ASASBIO
etoricoxib
NSAIDs
COX-2 Inhibitor
ARCOXIA 90 mg
BASDAI Bath Ankylosing Spondylitis Disease Activity Index
Lead sponsor: Spanish Foundation of Rheumatology
Sponsor class: OTHER
First posted: 2010-03-24
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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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Primary outcomes:
measure: the Percentage of Patients Fulfilling the Assessment Study (ASAS) Response Criteria Were Determined
timeFrame: the ASAS response were evaluated at week 2 and 4 and after 6 months treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Central Hospital of Asturias
state: Asturias
city: Sabadell
country: Spain
facility: Parc Tauli Hospital
state: Barcelona
city: Barcelona
country: Spain
facility: Sant Rafael Hospital
city: Barcelona
country: Spain
facility: Clinic I Provincial Hospital
city: Barcelona
country: Spain
facility: Bellvitge Hospital
city: Cordoba
country: Spain
facility: Reina Sofia University Hospital
city: Madrid
country: Spain
facility: Ramon Y Cajal Hospital
city: Madrid
country: Spain
facility: University Hospital 12 Octubre
city: Madrid
country: Spain
facility: Puerta de Hierro Hospital
city: Madrid
country: Spain
facility: Hospital General of Mostoles
city: Madrid
country: Spain
facility: University Hospital de la Princesa
city: Murcia
country: Spain
facility: Virgen de la Arrixaca Hospital
city: Salamanca
country: Spain
facility: Hospital Clinic of Salamanca
city: Tarragona
country: Spain
facility: Sant Pau i Santa Tecla Hospital
Study officials:
affiliation: Parc Tauli Hospital
name: Jordi Gratacós, PhD/ MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Reina Sofia Hospital
name: Eduardo Collantes Estevez, PhD/ MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bellvitge Hospital
name: Xavier Juanola Roura, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic i Provincial Barcelona
name: Raimon Sanmartí Sala, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Puerta de Hierro Hospital
name: Juan Mulero Mendoza, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: San Rafael Hospital
name: Estefania Moreno Ruzafa, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virgen de la Arrixaca Hospital
name: Luis Francisco Linares Ferrando, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Asturias Hospital
name: Rubén Queiro Silva, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ramon y Cajal Hospital
name: Elia Brito Brito, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic of Salamanca
name: Carlos Alberto Montilla Morales, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: General de Mostoles Hospital
name: Maria Cruces Fernández Espartero, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital 12 de Octubre
name: Pilar Fernández Dapica, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital de la Princesa
name: Rosario García de Vicuña, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sant Pau i Santa Tecla Hospital
name: Rosa Morlá, PhD/MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Estévez, E. Collantes, and A. Escudero Contreras.
citation: Sociedad Española de reumatología: estudio EPISER. Prevalencia de las enfermedades reumáticas en la población española. Reumatología. Madrid, Merck, Sharp & Dohme, 2001.
citation: 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.
citation: 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.
citation: 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.