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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01752335
Recruitment Status : Unknown
Verified February 2017 by Hospital Universitario de Canarias.
Recruitment status was:  Active, not recruiting
First Posted : December 19, 2012
Last Update Posted : February 9, 2017
Roche Pharma AG
Information provided by (Responsible Party):
Hospital Universitario de Canarias

Brief Summary:

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 or disease Intervention/treatment Phase
Rheumatoid Arthritis Other: Braquial ecography Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Effect of Monoclonal Anti-IL6 Antibody (Tocilizumab) on the Cardiovascular Risk in Patients With Rheumatoid Arthritis
Study Start Date : December 2011
Estimated Primary Completion Date : March 2017
Estimated Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Tocilizumab

Arm Intervention/treatment

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.

Primary Outcome Measures :
  1. Framingham Point Scores [ Time Frame: Baseline and 52 weeks ]
    Proportion of changes in Framingham Point Scores

Secondary Outcome Measures :
  1. Liver enzymes [ Time Frame: Baseline, 12, 24 and 52 weeks ]
    Number of patients with liver enzymes elevated.

  2. Lipoprotein levels [ Time Frame: Baseline, 12, 24 and 52 weeks ]
    Number of patients with elevated lipoprotein levels

  3. DAS28 score [ Time Frame: Baseline and 52 week ]
    Variation in DAS28 score after tocilizumab

  4. Number of patients with Adverse Drug Reactions [ Time Frame: up to 52 weeks ]
    Number of patients with Adverse Drug Reactions as a measure of safety

  5. Insulinemia [ Time Frame: Baseline and 52 week ]
    Change in insulinemia 52 weeks later.

Other Outcome Measures:
  1. Proportion of brachial artery vasodilation [ Time Frame: Baseline, 24 and 52 weeks ]
    To evaluate the endothelial responses to ischemia and vasodilatation by ecography

  2. cytokines, adipokines and adhesion molecules levels [ Time Frame: Baseline and 52 week ]
    To evaluate changes in cytokines, adipokines and adhesion molecules

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01752335

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Hospital Universitario de Canarias
La Laguna, Santa Cruz de Tenerife, Spain, 38320
Sponsors and Collaborators
Hospital Universitario de Canarias
Roche Pharma AG
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Principal Investigator: Federico Díaz González, MD, PhD Hospital Universitario de Canarias
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Responsible Party: Hospital Universitario de Canarias Identifier: NCT01752335    
Other Study ID Numbers: FRC-TOC-2009-01
2010-018658-12 ( EudraCT Number )
First Posted: December 19, 2012    Key Record Dates
Last Update Posted: February 9, 2017
Last Verified: February 2017
Keywords provided by Hospital Universitario de Canarias:
Rheumatoid Arthritis, tocilizumab, cardiovascular risk factors
Additional relevant MeSH terms:
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Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases