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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT04564001
Date of registration: 21/09/2020
Prospective Registration: Yes
Primary sponsor: Assistance Publique - Hôpitaux de Paris
Public title: Multicentre, Randomized, Prospective Trial Evaluating the Efficacy and Safety of Infliximab to Tocilizumab in Refractory or Relapsing Takayasu Arteritis INTOReTAK
Scientific title: Multicentre, Randomized, Prospective Trial Evaluating the Efficacy and Safety of Infliximab to Tocilizumab in Refractory or Relapsing Takayasu Arteritis
Date of first enrolment: September 2020
Target sample size: 50
Recruitment status: Not yet recruiting
URL:  https://clinicaltrials.gov/show/NCT04564001
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
Contacts
Name:     Tristan MIRAULT
Address: 
Telephone: +33156093051
Email: tristan.mirault@aphp.fr
Affiliation: 
Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of Takayasu disease according to the international criteria of the American
College of Rheumatology (ACR)

- Age at disease onset < 40 years

- Claudication of extremities

- Decreased brachial artery pulse (one or both arteries)

- Blood pressure difference of >10mm Hg between the arms

- Bruit over subclavian arteries or aorta

- 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

- Systemic features

- Elevated erythrocyte sedimentation rate

- Features of vascular ischemia or inflammation

- Typical angiographic features

- Refractory/relapsing disease

- Failure of disease to respond to daily corticosteroids therapy (1mg/kg/day for >
1month), i.e. disease still active

- Inability to taper corticosteroids below 10mg/day within 6 months

- Inability to discontinue corticosteroids after 1 year of treatment

- Relapse of disease after gradual decrease of corticosteroids therapy

- 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:

- Active Tuberculosis infection treatment achieved

- Completion of at least 3 weeks treatment for Latent Tuberculosis infection

- Negative tuberculin skin test (TST) or interferon-gamma release assay (IGRA)
(e.g., QuantiFERON®-TB Gold or T-spot TB® Test)

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

1. Treatment with biologic therapy (infliximab, adalimumab, certolizumab pegol,
golimumab, anakinra, tocilizumab, etanercept, abatacept, ixekizumab, secukinumab,
ustekinumab, alemtuzumab) within 6 months prior to enrollment

2. Past treatment with rituximab within the past 12 months, or past treatment with
rituximab more than 12 months ago where the B lymphocytes count has not returned
to normal at time of enrollment

3. Treatment with any systemic alkylating agents within 6 months prior to enrollment
(e.g., cyclophosphamide, chlorambucil)

- Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)

- Presence of any of the following disease processes:

- Microscopic polyangiitis

- Granulomatosis with polyangiitis

- Eosinophilic granulomatosis with polyangiitis

- Polyarteritis nodosa

- Cogan's syndrome

- Behcet's disease

- Sarcoidosis

- Kawasaki's disease

- Atypical mycobacterial infections

- Deep fungal infections

- Lymphoma, lymphomatoid granulomatosis, or other type of malignancy tha mimics
vasculitis

- Cryoglobulinemic vasculitis

- Systemic lupus erythematosus

- Rheumatoid arthritis

- Mixed connective tissue disease or any overlap autoimmune syndrome

- Known constitutive immunodeficiency



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Takayasu Arteritis
Intervention(s)
Drug: Infliximab
Drug: Tocilizumab
Primary Outcome(s)
Proportion of patients with prednisone = 0.1mg/kg per day and sustained inactive disease (NIH score = 1) from M3 to M6 and same biological therapy from randomization [Time Frame: at 6 months after randomization]
Secondary Outcome(s)
Cumulative doses of prednisone [Time Frame: at 12 months after randomization]
Cumulative doses of prednisone [Time Frame: at 6 months after randomization]
Incidence of adverse events of grades III and IV [Time Frame: at 12 months after randomization]
Incidence of adverse events of grades III and IV [Time Frame: at 6 months after randomization]
Incidence of relapse as defined by the NIH criteria [Time Frame: between 3 and 6 months]
Incidence of revascularization procedures [Time Frame: at 12 months after randomization]
Incidence of revascularization procedures [Time Frame: at 6 months after randomization]
Incidence of traitement failure [Time Frame: at 3 months after randomization]
Proportion of new vascular lesions [Time Frame: at 12 months]
Proportion of new vascular lesions [Time Frame: at 6 months]
Quality of life [Time Frame: at 12 months]
Quality of life will be assessed using the SF36 questionnaire [Time Frame: at 6 months]
Secondary ID(s)
P160909
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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