Informations générales (source: ClinicalTrials.gov)
Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease : Multicentric Randomized Phase III Trial
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
février 2021
janvier 2024
11 septembre 2025
"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."
Etablissements
Critères
Tous
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 antibodies
routinely 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 bearing
potential)
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
study treatment
9. Males who are sexually active with women of childbearing potential must agree to
follow instructions for method(s) of contraception for the duration of study
treatment and 6 months after the last dose of study treatment
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 antibodies
routinely 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 bearing
potential)
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
study treatment
9. Males who are sexually active with women of childbearing potential must agree to
follow instructions for method(s) of contraception for the duration of study
treatment and 6 months after the last dose of study treatment
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 to
adhesion 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 ventricular
arrhythmias
13. Concomitant use of drugs prolonging QT / QTc (list of treatments in annex)
14. Hypokalemia
15. Patients with pulmonary hypertension detected on echocardiography during the
screening/selection visit (systolic pulmonary artery pressure (PAP) was 37-50 mmHg,
and/or tricuspid regurgitation velocity 2.8-3.4 ms-1) are excluded.