Effect of Monoclonal Anti-IL6 Antibody (Tocilizumab) on the Cardiovascular Risk in Patients With Rheumatoid Arthritis (TOCRIVAR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Hospital Universitario de Canarias
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Hospital Universitario de Canarias
ClinicalTrials.gov Identifier:
NCT01752335
First received: December 3, 2012
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

The purpose of this study is to determine whether tocilizumab changes the cardiovascular risk factors on patients with arthritis rheumatoid.

Study hypothesis: the IL-6 contributes to increase the cardiovascular risk factors of patients with rheumatoid arthritis because it produces systemic effects as increasing weight and atherogenic body fat, changing energy homeostasis and inducing the adipokines production and the insulin resistence.


Condition Intervention Phase
Rheumatoid Arthritis
Other: Braquial ecography
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Effect of Monoclonal Anti-IL6 Antibody (Tocilizumab) on the Cardiovascular Risk in Patients With Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Hospital Universitario de Canarias:

Primary Outcome Measures:
  • Framingham Point Scores [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: Yes ]
    Proportion of changes in Framingham Point Scores


Secondary Outcome Measures:
  • Liver enzymes [ Time Frame: Baseline, 12, 24 and 52 weeks ] [ Designated as safety issue: Yes ]
    Number of patients with liver enzymes elevated.

  • Lipoprotein levels [ Time Frame: Baseline, 12, 24 and 52 weeks ] [ Designated as safety issue: Yes ]
    Number of patients with elevated lipoprotein levels

  • DAS28 score [ Time Frame: Baseline and 52 week ] [ Designated as safety issue: No ]
    Variation in DAS28 score after tocilizumab

  • Number of patients with Adverse Drug Reactions [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]
    Number of patients with Adverse Drug Reactions as a measure of safety

  • Insulinemia [ Time Frame: Baseline and 52 week ] [ Designated as safety issue: Yes ]
    Change in insulinemia 52 weeks later.


Other Outcome Measures:
  • Proportion of brachial artery vasodilation [ Time Frame: Baseline, 24 and 52 weeks ] [ Designated as safety issue: Yes ]
    To evaluate the endothelial responses to ischemia and vasodilatation by ecography

  • cytokines, adipokines and adhesion molecules levels [ Time Frame: Baseline and 52 week ] [ Designated as safety issue: No ]
    To evaluate changes in cytokines, adipokines and adhesion molecules


Estimated Enrollment: 28
Study Start Date: December 2011
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
tocilizumab

All the patients are treated with tocilizumab before inclusion. The doses, frequency and duration are in acordance with the Summary of Characteristics of the Product authorised by EMA.

Usually 8mg/kg (not minor than 480 mg), once each 4 weeks.

Other: Braquial ecography
At the moment of the ecography, the clinician evaluates the endothelial responses via applying braquial ischemia and administering sublingual nitroglicerin spray to evaluate vasodilation.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 and <70 years.
  2. Diagnosis of active Rheumatoid Arthritis, moderate to severe (≥ 3.2 DAS28) of ≥ 6 months duration.
  3. Patients with an inadequate clinical response to a stable dose of non-biological DMARDs or anti-TNF treatment for a period ≥ 8 weeks before treatment.
  4. If patients are receiving oral corticosteroids, the dose should have been ≤ 10 mg predinosona and stable for at least one month before the start of treatment (day 1).
  5. Patients who are able and wish to sign the informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

  1. Major surgery (including joints surgery) within eight weeks prior to the screening visit or major surgery scheduled for six months after first infusion.
  2. Other Rheumatic autoimmune diseases, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis or systemic involvement secondary to AR (such as vasculitis, pulmonary fibrosis or Felty's syndrome). It's allowed the inclusion of patients with interstitial pulmonary fibrosis and be still able to tolerate treatment with MTX. Sjögren's syndrome with RA is not considered exclusion criterion.
  3. Rheumatoid arthritis with Functional Class IV as defined in the RA Classification of the ACR (complete or significant disability of patients, confined to bed or to the wheelchair and without possibilities to take care themselves).
  4. Prior or actual inflammatory joint disease different of RA (eg, gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease).

    Specific drug criteria

  5. Treatment with any investigational agent in the four weeks before the screening visit (or time equivalent to five half-lives of the investigational drug, whichever is longer).
  6. Immunization with a live vaccine / attenuated in the four weeks prior to the baseline visit.
  7. Pretreatment with TCZ Laboratory Tests (at the screening visit)
  8. Serum creatinine> 142 mmol / l (1.6 mg / dL) in women and> 168 mmol / l (1.9 mg / dl) in men and absence of active renal disease.
  9. ALT (SGPT) and AST (SGOT)> 1.5 ULN (if the initial sample of ALT [SGPT] or AST [SGOT] gives a value> 1.5 times ULN, you can take and analyze a second sample during the selection period).
  10. Platelet count <100 x 109 / l (100.000/mm3).
  11. Hemoglobin <85 g / dl (<8.5 g / l, 5.3 mmol / l).
  12. Leukocytes <1.0 x 109 / l (1000/mm3), ANC <0.5 x 109 / L (500/mm3).
  13. RAL <0.5 x 109 / L (500/mm3).
  14. Positivity for surface antigen of hepatitis B (HBsAg) and antibodies to hepatitis C.
  15. Total bilirubin> ULN (if the initial sample of bilirubin> ULN, you can take and analyze a second sample during the selection period).
  16. Triglycerides> 10 mmol / l (> 900 mg / dl) at the screening visit (non fasting).
  17. Pregnant or lactating women.
  18. not use of reliable means of contraception, such as a physical barrier (patient and partner), pill or contraceptive patch, spermicide and barrier or IUD.
  19. Background of serious allergic or anaphylactic reactions to human monoclonal antibodies, humanized or murine.
  20. RXT evidence of clinically significant abnormality.
  21. Evidence of uncontrolled concomitant serious illness, cardiovascular, nervous system, lung (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal.
  22. history of diverticulitis, diverticulosis in antibiotic treatment, the physician should consider the benefit-risk ratio.
  23. Background of lower GI ulcer disease as the Crohn's disease, ulcerative colitis or other symptomatic conditions predisposed to perforations lower GI
  24. Uncontrolled diseases such as asthma, psoriasis or inflammatory bowel disease,... treated normally with corticosteroids orally or parenterally.
  25. Ongoing liver disease as determined by the principal investigator. (Patients with a history of elevated ALT (SGPT) will not be excluded)
  26. Active infections or recurrent infections in the past by mycobacteria, fungus, virus or bacteria (for example: tuberculosis, atypical mycobacterial disease, clinically significant abnormalities in RXT, hepatitis B and C, herpes zoster), or any major episode infection that required hospitalization or IV antibiotic treatment in the 4 weeks preceding the screening visit or oral antibiotic in the 2 weeks prior to the screening visit.
  27. Primary or secondary immunodeficiency.
  28. Evidence of active malignancy diagnosed within 5 years before the inclusion(including solid tumors and hematological), or breast cancer diagnosed in the previous 5 years.
  29. Active tuberculosis (TB) requiring treatment within 3 years above. Patients with a positive skin test tuberculin purified protein derivative (PPD) at the screening visit. Patients treated for tuberculosis no recurrence in the last three years will not be excluded.
  30. HIV positive patients.
  31. History of alcoholism, drug addiction or drug abuse in the six months before the screening visit.
  32. Painful neuropathies or other conditions that may interfere with the pain assessment.
  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: NCT01752335

Contacts
Contact: Federico Díaz, MD,PhD federico.diaz.gonzalez@gmail.com
Contact: Vanesa Hernández, MD

Locations
Spain
Hospital Universitario de Canarias Recruiting
La Laguna, Santa Cruz de Tenerife, Spain, 38320
Contact: Vanessa Hernández, MD       mvhhernandez@yahoo.es   
Principal Investigator: Federico González, MD,PhD         
Sub-Investigator: Vanessa Hernández, MD         
Sponsors and Collaborators
Hospital Universitario de Canarias
Roche Pharma AG
Investigators
Principal Investigator: Federico Díaz González, MD, PhD Hospital Universitario de Canarias
  More Information

No publications provided

Responsible Party: Hospital Universitario de Canarias
ClinicalTrials.gov Identifier: NCT01752335     History of Changes
Other Study ID Numbers: FRC-TOC-2009-01, 2010-018658-12
Study First Received: December 3, 2012
Last Updated: December 19, 2012
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Hospital Universitario de Canarias:
Rheumatoid Arthritis, tocilizumab, cardiovascular risk factors

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 16, 2014