Status and phase
Conditions
Treatments
About
Takayasu arteritis (TA) is a vasculitis of unknown origin, resulting in progressive thickening and stenosis of large and medium arteries (the aorta and its major branches, and the pulmonary arteries). First line therapy of TA consists of high dose corticosteroids (CS). Between 20 and 50% of cases respond to CS alone, with subsequent resolution of symptoms and stabilization of vascular abnormalities. Although second-line agents (methotrexate, azathioprine, mercaptopurine, mycophenolate mofetil) may result in initial remission, relapses remain common when prednisone is tapered. Thus, 50% of CS-resistant or relapsing TA patients may achieve sustained remission with the addition of methotrexate. During the last decade, biologics such as anti-tumor necrosis factor alpha (anti-TNFα) and anti-interleukin-6 (anti-IL-6) have been used as third-line treatment in refractory or relapsing TA. Almost 90% of CS-methotrexate resistant TA cases responded to infliximab, an anti-TNFα, and sustained remission was obtained in 37 to 76% of the cases. Tocilizumab, an anti-IL-6 has given similar results with 68% of sustained remission in refractory TA. Irrespective of classical cardiovascular risk factors, the systemic inflammation and CS use play a pivotal role in the occurrence of cardiovascular thrombotic events (CVEs). As CVEs overlap with TA complications it is primordial to drastically taper CS in that vasculitis. We therefore hypothesize that Infliximab or Tocilizumab can achieve a remission in more than 70% of refractory/relapsing TA cases to CS associated to a second-line agent. INTOReTAK, first randomized prospective study in TA, has an original design testing Infliximab and Tocilizumab propensity to achieve over 70% of sustained remission in refractory/relapsing TA and evaluating jointly the 2 arms. The primary objective of this study is to obtain, by arm, ≥ 70% of patients at 6 months after randomization with prednisone ≤ 0.1mg/kg per day and inactive disease (NIH score ≤ 1) during the last 3 months.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Diagnosis of Takayasu disease according to the international criteria of the American College of Rheumatology (ACR)
Active disease according to the international criteria of the National Institute of Health (NIH)
New onset or worsening of at least two of the following four criteria
Refractory/relapsing disease
Patients with one immunosuppressive agent (methotrexate, azathioprine, mercaptopurine or mycophenolate mofetil)
Age of 18 years or older
Weight 40 - 120 kg
Medical follow-up in a university or general hospital in France
Social insurance
Willing and able to provide written informed consent
Willing and able to comply with treatment and follow-up procedures required by the study protocol
For female subjects of child-bearing age, a negative serum pregnancy test and no pregnancy plans within 12 months
For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study. Adequate contraceptive measures include hormonal methods used for two or more cycles prior to Screening (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, or condom used in conjunction with contraceptive foam or jelly), intrauterine methods (IUD), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence.
Chest X-ray results (postero-anterior and lateral) within 12 weeks prior to enrollment with no evidence of active tuberculosis, active infection, or malignancy
Tuberculosis assessment:
Exclusion criteria
Active tuberculosis or untreated latent tuberculosis
Evidence of active infection (includes chronic infection)
Infection requiring treatment with antibiotics within 2 weeks prior to enrollment
Infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen.
Pregnancy or lactation
Inability to comply with study guidelines
Inability to provide informed consent
Immunosuppressant type or dose modification within 30 days prior to enrollment
Alcohol or drug abuse, that, in the investigator's opinion, could prevent a subject from fulfilling the study requirements or that would increase the risk of study procedures
Severe renal insufficiency (creatinine clairance <30mL/min/1,73m2)
Hepatic dysfunction as shown by aspartate transaminase (AST) or alanine transaminase (ALT) levels >5-fold the upper limit of normal
Heart failure ≥ stage III / IV NYHA,
History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin, or solid tumors treated with curative therapy and disease free for at least 5 years.
History of multiple sclerosis and/or demyelinating disorder
History of severe allergic or anaphylactic reactions to infliximab, any chimeric murine monoclonal antibody, tocilizumab, and their respective excipients or prednisone
History of immediate hypersensitivity reaction to iodinated and gadolinium-based contrast media
Cytopenia: Hemoglobin < 8.5 g/dL, absolute neutrophil < 1.5 G/L, Platelet count < 80 G/L
Any live (attenuated) vaccine fewer than 4 weeks before enrolment. Recombinant or killed virus vaccines fewer than 2 weeks before enrolment.
Use of the following systemic treatments during the specified periods
Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)
Presence of any of the following disease processes:
Primary purpose
Allocation
Interventional model
Masking
50 participants in 2 patient groups
Loading...
Central trial contact
Matthieu Resche-Rigon; Tristan MIRAULT
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal