Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease

Last updated: February 6, 2021
Sponsor: Assistance Publique - Hôpitaux de Paris
Overall Status: Active - Recruiting

Phase

3

Condition

Myositis

Lung Disease

Treatment

N/A

Clinical Study ID

NCT03770663
P140217
2016-002921-12
  • Ages > 18
  • All Genders

Study Summary

"Antisynthetase syndrome (ASS) is one of the most severe inflammatory myopathy (IM), due to pulmonary involvement (interstitial lung disease, ILD). Until now, the most commonly used immunosuppresive therapy in Europe is Cyclophosphamide followed by different immunosuppressive drugs as maintenance therapy, including Azathioprine (and so called " European Strategy "). In the USA however, the first-line immunosuppressive treatment is Tacrolimus (so called " American Strategy "). None of these two different strategies has ever been studied prospectively, and there is no clear comparison of short and long-term treatment efficacy and tolerance. Thus, there are yet no evidences helping the clinicians in the therapeutic management of patients with ASS-related ILD.

  The aim of this study is therefore to compare both strategies as first line treatments or in
  relapsing patients : CATR.PAT study is a 52 weeks, randomized, comparative, controlled,
  open-labeled, phase III, therapeutic clinical trial, comparing two treatment strategies."

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age ≥ 18
  2. Signed informed consent
  3. Affiliation to the Social security system
  4. Diagnosis of ASS: positive test for any of the 5 anti-tRNA synthetase antibodiesroutinely tested (ELISA, Luminex or Linear-dot), including anti-Jo-1, anti-PL7,anti-PL12, anti-EJ and anti-OJ.
  5. Diagnosis of ILD-related ASS: interstitial lung disease on HRCT.
  6. Moderate to severe ILD on PFT : FVC < 80% and or cDLCO < 70%
  7. beta-HCG test negative or negative uterine echography (for women of child bearingpotential)
  8. Women of childbearing potential must have an oral contraception (macroprogestatifs)during all the duration of study treatment and 12 months after the last dose of studytreatment
  9. Males who are sexually active with women of childbearing potential must agree tofollow instructions for method(s) of contraception for the duration of study treatmentand 6 months after the last dose of study treatment

Exclusion

Exclusion Criteria:

  1. Pregnancy and/or breast feeding
  2. Others contraindications to the treatments, including hypersensitivity to the drug (including excipient and active compounds), medical contraception contraindications,severe renal failure, severe hepatic insufficiency and severe psychiatric disorders.Specific contraindications are listed for each experimental medication in Table 6 (according to updated Summary of product characteristics, see Appendix 8)
  3. Fever or active bacterial infection (ie. septicemia, pneumopathy, pyelonephritis,acute prostatitis …), or parasitic infection (ie. Anguillulosis …),or fungal infection (ie. Invasive pulmonary aspergillosis …), or viral infection (HIV seropositivity,Active Tuberculosis, active B/C viral hepatitis, CMV, active EBV…)
  4. Active neoplasm
  5. Previous inefficacy of Cyclophosphamide, Azathioprine or Tacrolimus, not related toadhesion problems.
  6. Previous use of 3 daily IV steroids < 3 months before patient's enrollment.
  7. ASS-related ILD worsening or relapse under Prednisone > 0.5 mg/kg/day
  8. Previous use of Cyclophosphamide, Azathioprine or Tacrolimus in the last 6 months.
  9. Severe ASS requiring ICU (respiratory disease, myocarditis), plasma exchange or IV-Ig.
  10. Positivity of auto-antibodies associated to Systemic Sclerosis (anti-Telomerase,anti-Centromères, anti-Polymerase III).
  11. Patients with QTc > 450 msec
  12. Patients with history of long QT syndrome (including familial) or ventriculararrhythmias
  13. Concomitant use of drugs prolonging QT / QTc (list of treatments in annex)
  14. Hypokalemia
  15. Patients with pulmonary hypertension detected on echocardiography during thescreening/selection visit (systolic pulmonary artery pressure (PAP) was 37-50 mmHg,and/or tricuspid regurgitation velocity 2.8-3.4 ms-1) are excluded.

Study Design

Total Participants: 76
Study Start date:
February 05, 2021
Estimated Completion Date:
January 02, 2024

Study Description

"During the study period, according to randomization into two groups (n=38 patients, respectively), patients will receive either:

  - Group 1 &amp; 2 : 3 IV pulses of Methylprednisolone (7.5 mg/kg/day followed by tapering doses
  of oral Prednisone, started at 1 mg/kg/day from D4 to M12

  In association with :

    -  Group 1 : European Standard of care :

       6 IV pulses of Cyclophosphamide (1000 mg) followed from M5 to M12 by oral Azathioprine
       (2 mg/kg/day), with a maximum of 150 mg/d)

    -  Group 2 : American Strategy Tacrolimus is given orally from M0 to M12 (started at the
       initial dose of 2x2mg/d). Tacrolimus doses are regularly adapted to its serum
       concentration to reach 5-15 ng/ml."

Connect with a study center

  • Hôpital Universitaire Pitié Salpêtrière

    Paris, 75013
    France

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.