Status:
UNKNOWN
Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease
Lead Sponsor:
Assistance Publique - Hôpitaux de Paris
Conditions:
Antisynthetase Syndrome (ASS)
Interstitial Lung Disease
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief 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 t...
Detailed Description
"During the study period, according to randomization into two groups (n=38 patients, respectively), patients will receive either: \- Group 1 \& 2 : 3 IV pulses of Methylprednisolone (7.5 mg/kg/day fo...
Eligibility Criteria
Inclusion
- Age ≥ 18
- Signed informed consent
- Affiliation to the Social security system
- 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.
- Diagnosis of ILD-related ASS: interstitial lung disease on HRCT.
- Moderate to severe ILD on PFT : FVC \< 80% and or cDLCO \< 70%
- beta-HCG test negative or negative uterine echography (for women of child bearing potential)
- 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
- 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
- Pregnancy and/or breast feeding
- 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)
- 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…)
- Active neoplasm
- Previous inefficacy of Cyclophosphamide, Azathioprine or Tacrolimus, not related to adhesion problems.
- Previous use of 3 daily IV steroids \< 3 months before patient's enrollment.
- ASS-related ILD worsening or relapse under Prednisone \> 0.5 mg/kg/day
- Previous use of Cyclophosphamide, Azathioprine or Tacrolimus in the last 6 months.
- Severe ASS requiring ICU (respiratory disease, myocarditis), plasma exchange or IV-Ig.
- Positivity of auto-antibodies associated to Systemic Sclerosis (anti-Telomerase, anti-Centromères, anti-Polymerase III).
- Patients with QTc \> 450 msec
- Patients with history of long QT syndrome (including familial) or ventricular arrhythmias
- Concomitant use of drugs prolonging QT / QTc (list of treatments in annex)
- Hypokalemia
- 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.
Key Trial Info
Start Date :
February 5 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
January 2 2024
Estimated Enrollment :
76 Patients enrolled
Trial Details
Trial ID
NCT03770663
Start Date
February 5 2021
End Date
January 2 2024
Last Update
February 9 2021
Active Locations (1)
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1
Hôpital Universitaire Pitié Salpêtrière
Paris, France, 75013