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

• Status: Recruiting
• Trial end date: 2024-01-02
• Target enrollment: 0
• Participant gender: All

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."

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Azathioprine; Cyclophosphamide; Methylprednisolone; Tacrolimus

Criteria

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

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 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.