Evaluation of a Standardized Protocol for Dose Reduction in Patients With Spondylarthropathies and Clinical Remission With Anti-TNF Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by Spanish Clinical Pharmacology Society
Sponsor:
Collaborator:
Spanish reumatology Society
Information provided by (Responsible Party):
Dra. Caridad Pontes, Spanish Clinical Pharmacology Society
ClinicalTrials.gov Identifier:
NCT01604629
First received: May 17, 2012
Last updated: August 21, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to demonstrate that patients with Spondylarthropathies in remission under antiTNF therapy, can maintain the remission with a maintenance dose inferior to the currently recommended dose schedule.


Condition Intervention Phase
Spondylarthropathies
Drug: Reduced doses of anti-TNF
Drug: Stable doses of anti-TNF
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Clinical Value of Standardized Protocol for Dose-reduction in Patients With Spondylarthropathies and Clinical Remission With Anti-TNF Therapy: Open-label, Controlled, Randomized, Multicenter Trial.

Resource links provided by NLM:


Further study details as provided by Spanish Clinical Pharmacology Society:

Primary Outcome Measures:
  • Proportion of patients who are kept in the acceptable therapeutic objective according Spanish Rheumatology Society (SER) consensus, after one year [ Time Frame: one year after inclusion ] [ Designated as safety issue: No ]
    Proportion of patients who are kept in the acceptable therapeutic objective according Spanish Society of Reumatology (SER) consensus (BASDAI < 4, global clinical impression by physician <4 and by patient < 4 and axial nocturnal pain <4) after one year


Secondary Outcome Measures:
  • Proportion of patients in remission one year after inclusion in the study [ Time Frame: one year ] [ Designated as safety issue: No ]
    Proportion of patients in remission, defined as ASDAS-C score lower than than 1.3, after one year from inclusion in the study

  • Proportion of patients who experience a clinical reactivation [ Time Frame: last study visit (up to 3 years or December 2014) ] [ Designated as safety issue: No ]
    Proportion of patients who experience a clinical reactivation, defined according criteria of active disease by Spanish Society of Reumatology (SER) consensus (BASDAI > 4, global clinical impression by physician >4 and at least one of three following criteria: patient impression >= 4, axial nocturnal pain (VAS) >= 4, and increased of acute phase reactants (reactive C protein (PCR) and/or erytrocyte sedimentation rate (ESR))

  • Proportion of patients who are kept in the acceptable therapeutic objective in the last study visit [ Time Frame: last study visit (up to 3 years or December 2014) ] [ Designated as safety issue: No ]
    Proportion of patients who are kept in the acceptable therapeutic objective according Spanish Society of Reumatology (SER) consensus (BASDAI < 4, global clinical impression by physician <4 and by patient < 4 and axial nocturnal pain <4) in the last study visit

  • Proportion of patients who are kept in the ideal therapeutic objective in the last follow visit [ Time Frame: last study visit (up to 3 years or December 2014) ] [ Designated as safety issue: No ]
    Proportion of patients who are kept in the ideal therapeutic objective according to the Spanish Society of Reumatology (SER) consensus (BASDAI < 2, global clinical impression by physician <2 and by patient < 2 ) in the last study visit

  • Time to clinical reactivation [ Time Frame: last study visit (up to 3 years or December 2014) ] [ Designated as safety issue: No ]
    Time to clinical reactivation, defined according to the criteria of active disease by Spanish Society of Reumatology (SER) consensus, BASDAI + VAS and ASDAS, respectively

  • Withdrawal because of clinical requirement to modify the antiTNF treatment. [ Time Frame: last study visit (up to 3 years or December 2014) ] [ Designated as safety issue: Yes ]
    Proportion of patients who are withdrawn from the study because of clinical requirement to modify the antiTNF treatment.

  • NSAIDs use [ Time Frame: last study visit (up to 3 years or December 2014) ] [ Designated as safety issue: No ]
    NSAIDs use measured according semiquantitative Dougados criteria

  • Suspected Serious Adverse Reactions [ Time Frame: last study visit (up to 3 years or December 2014) ] [ Designated as safety issue: Yes ]
    Proportion of patients who experience a Serious Adverse Event at least possibly related with anti-TNF therapy.

  • Time to Suspected Serious Adverse Reaction [ Time Frame: last study visit (up to 3 years or December 2014) ] [ Designated as safety issue: Yes ]
    Time to Serious Adverse Events at least possibly related with anti-TNF therapy

  • Proportion of patients in remission after two years from inclusion in the study [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Proportion of patients in remission, defined as ASDAS-C point less than 1.3, after two years from inclusion in the study


Estimated Enrollment: 190
Study Start Date: July 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Reduced doses of anti-TNF
Standardized schedule of reduced doses of anti-TNF, reached either through the interval spacing of administration (adalimumab, etanercept or golimumab) or reducing doses of infliximab
Drug: Reduced doses of anti-TNF
Standardized schedule of reduced doses of anti-TNF, reached either through the interval spacing of administration (adalimumab, etanercept or golimumab) or reducing doses of infliximab
Other Names:
  • Adalimumab: 40 mg / 3 weeks
  • Etanercept: 50 mg / 10 days
  • Golimumab: 50 mg / 6 weeks
  • Infliximab: 3 mg/kg / 8 weeks
Active Comparator: Stable doses of anti-TNF
Stable doses of anti-TNF according clinical practice based on approved summary product characteristics (SPC) and SER consensus about biological therapies in Ankylosing Spondylitis and other Spondylarthropathies, except Psoriatic Arthritis
Drug: Stable doses of anti-TNF
Stable doses of anti-TNF according clinical practice based on approved summary product characteristics (SPC) and SER consensus about biological therapies in Ankylosing Spondylitis and other Spondylarthropathies, except Psoriatic Arthritis
Other Names:
  • Adalimumab: 40 mg / 2 weeks
  • Etanercept: 25 mg / 3 days ó 50 mg /7 days
  • Golimumab: 50 mg / 4 weeks
  • Infliximab: 5 mg/kg / 6-8 weeks

Detailed Description:

It has been shown that the withdrawal of treatment follows with a flare of the disease in a short time after the suspension but it has not been evaluated in controlled trials if remission could be maintained with a lower dose. A multicenter, national, open-label, randomized and controlled clinical trial of 3 years duration (2 years for inclusion + 1 year follow-up) is proposed to address this issue. The study will include 190 patients with Spondylarthropathies in stable treatment with any single anti-TNF agent and compliance with criteria of clinical remission for at least 4 months. Patients will be randomized to intervention or control arm, with stratification according to the antiTNF product thet were receiving prior to inclusion. Patients will be followed with the calendar of visits recommended by the Spanish Society of Rheumatology for clinical practice. The proposed hypothesis is of non-inferiority of the experimental arm with dose reduction versus the control arm with standard treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients older than 18 years
  • Patients with Spondylarthropathies according ASAS group criteria.
  • Patients under treatment with anti-TNF therapy (infliximab, adalimumab, etanercept, golimumab) who present established clinical remission
  • Patients to give their informed consent to participate in the study

Exclusion Criteria:

  • Patients with secondary Spondylarthropathies
  • Patients with Spondylarthropathies and predominantly clinical of peripheral arthritis which receive anti-TNF therapy by peripheral symp tons.
  • Patients with Spondylarthropathies and other associated diseases that hinders or modify the clinical evaluation of the patient (fibromyalgia, chronic inflammatory disorders…)
  • Patients with bowel inflammatory disease
  • Patients under chronic therapy with anti-TNF therapy who received the patterns of reduction that will be explored in the experimental group, or low doses or most spaced that those in the experimental group before study inclusion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01604629

Contacts
Contact: Caridad Pontes, MD, PhD 00 34 93 723 10 10 cpontes@tauli.cat
Contact: Cristina Avendaño-Solá, MD 0034 91 191 64 79 cavendano.hpth@salud.madrid.org

Locations
Spain
Hospital Universitario Central de Asturias Not yet recruiting
Oviedo, Asturias, Spain
Contact: Rubén Queiro         
Principal Investigator: Rubén Queiro         
Hospital Monte Naranco Not yet recruiting
Oviedo, Asturias, Spain
Contact: Juan Carlos Torre         
Principal Investigator: Juan Carlos Torre         
Hospital General de Llerena-Zafra Not yet recruiting
Llerena, Badajoz, Spain
Contact: Raúl Veroz         
Principal Investigator: Raúl Veroz         
Hospital Universitario de Bellvitge Recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08907
Contact: Xavier Juanola, MD, PhD    00 34 93 260 7712    x.juanola@bellvitgehospital.cat   
Principal Investigator: Xavier Juanola, MD, PhD         
Corporació Sanitària Parc Taulí Recruiting
Sabadell, Barcelona, Spain, 08208
Contact: Jordi Gratacos, MD PhD    00 34 93 723 10 10    jgratacosmas@gmail.com   
Principal Investigator: Gratacos Jordi, MD, PhD         
Hospital de Sant Joan Despí Moisès Broggi Not yet recruiting
Sant Joan Despí, Barcelona, Spain
Contact: Dèlia Reina         
Principal Investigator: Dèlia Reina         
Hospital Comarcal de Palamós Not yet recruiting
Palamós, Girona, Spain
Contact: Teresa Clavaguera         
Principal Investigator: Teresa Clavaguera         
Hospital Son Llàtzer Not yet recruiting
Palma de Mallorca, Illes Balears, Spain
Contact: Antonio Juan         
Principal Investigator: Antonio Juan         
Hospital Universitario de Gran Canaria Dr. Negrín Not yet recruiting
Las Palmas de Gran Canaria, Las Palmas, Spain
Contact: Carlos Rodríguez         
Principal Investigator: Carlos Rodríguez         
Hospital Universitario Príncipe de Asturias Not yet recruiting
Alcalá de Henares, Madrid, Spain
Contact: Eduardo Cuende         
Principal Investigator: Eduardo Cuende         
Hospital Universitario Fundación Alcorcón Not yet recruiting
Alcorcón, Madrid, Spain
Contact: Pedro Zarco         
Principal Investigator: Pedro Zarco         
Hospital Universitario Puerta de Hierro Recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Jesús Sanz, MD    00 34 91 1917101    jessanz@terra.es   
Principal Investigator: Sanz Jesus, MD         
Hospital Universitario de Móstoles Not yet recruiting
Móstoles, Madrid, Spain
Contact: Mª Cruz Fernández-Espartero         
Principal Investigator: Mª Cruz Fernández-Espartero         
Hospital Clínic Universitari Sant Joan d'Alacant Not yet recruiting
Alacant, Spain
Contact: Enrique Batlle         
Principal Investigator: Enrique Batlle         
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Raimon Sanmarti, MD, PhD    00 34 93 2275400    gcalvo@clinic.ub.es   
Principal Investigator: Raimon Sanmarti, MD, PhD         
Hospital Vall d'Hebron Not yet recruiting
Barcelona, Spain
Contact: Agustí Sellas         
Principal Investigator: Agustí Sellas         
IMIM-Hospital del Mar Not yet recruiting
Barcelona, Spain
Contact: Joan Maymó         
Principal Investigator: Joan Maymó         
Hospital Reina Sofía Not yet recruiting
Córdoba, Spain
Contact: Eduardo Collantes         
Principal Investigator: Eduardo Collantes         
Hospital Universitario de Guadalajara Not yet recruiting
Guadalajara, Spain
Contact: Manuel Fernández-Prada         
Principal Investigator: Manuel Fernández-Prada         
Hospital Juan Canalejo Not yet recruiting
La Coruña, Spain
Contact: José Luís Fernández-Sueiro         
Principal Investigator: José Luís Fernández-Sueiro         
Hospital Universitario 12 de Octubre Not yet recruiting
Madrid, Spain
Contact: Mª Pilar Fernández-Dapica         
Principal Investigator: Mª Pilar Fernández-Dapica         
Hospital Universitario La Paz Not yet recruiting
Madrid, Spain
Contact: Eugenio De Miguel         
Principal Investigator: Eugenio De Miguel         
Hospital General Universitario Gregorio Marañón Not yet recruiting
Madrid, Spain
Contact: Carlos González         
Principal Investigator: Carlos González         
Hospital Universitario Ramón y Cajal Not yet recruiting
Madrid, Spain
Contact: Consuelo Díaz-Miguel         
Principal Investigator: Consuelo Díaz-Miguel         
Hospital Clínico San Carlos Not yet recruiting
Madrid, Spain
Contact: Juan Ángel Jover         
Principal Investigator: Juan Ángel Jover         
Hospital Universitario de La Princesa Not yet recruiting
Madrid, Spain
Contact: Rosario García-Vicuña         
Principal Investigator: Rosario García-Vicuña         
Hospital Universitario Virgen de la Arrixaca Not yet recruiting
Murcia, Spain
Contact: Luis Francisco Linares         
Principal Investigator: Luís Francisco Linares         
Hospital Clínico de Salamanca Not yet recruiting
Salamanca, Spain
Contact: Carlos Alberto Montilla         
Principal Investigator: Carlos Alberto Montilla         
Hospital Universitario Virgen Macarena Not yet recruiting
Sevilla, Spain
Contact: Rafael Ariza         
Principal Investigator: Rafael Ariza         
Hospital Sant Pau i Santa Tecla Not yet recruiting
Tarragona, Spain
Contact: Rosa María Morlà         
Principal Investigator: Rosa María Morlà         
Hospital General de Valencia Not yet recruiting
Valencia, Spain
Contact: Cristina Campos         
Principal Investigator: Cristina Campos         
Sponsors and Collaborators
Spanish Clinical Pharmacology Society
Spanish reumatology Society
Investigators
Principal Investigator: Gratacós Jordi, MD, PhD Hospital de Sabadell - Corporació Sanitària i Universitaria Parc Taulí UAB
  More Information

No publications provided

Responsible Party: Dra. Caridad Pontes, Study coordinator, Spanish Clinical Pharmacology Society
ClinicalTrials.gov Identifier: NCT01604629     History of Changes
Other Study ID Numbers: REDES-TNF/2012, 2011-005871-18
Study First Received: May 17, 2012
Last Updated: August 21, 2012
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Spanish Clinical Pharmacology Society:
Spondylarthropathies
Persistent clinical remission with anti-TNF therapy
Standardized protocol for dose reduction anti-TNF therapy

Additional relevant MeSH terms:
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
TNFR-Fc fusion protein
Infliximab
Adalimumab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on August 01, 2014