A Trial of Tadalafil in Interstitial Lung Disease of Scleroderma
Status:
Completed
Trial end date:
2014-05-01
Target enrollment:
Participant gender:
Summary
Systemic sclerosis (SSc, scleroderma) is a multisystem autoimmune rheumatic disease that
causes inflammation, vascular damage and fibrosis. Besides involvement of skin, fibrosis also
affects lung and heart. Although advances in understanding in pathophysiology and use of
immunosuppressive therapy has brought significant improvement in outcome of other autoimmune
diseases, scleroderma still remains as a disease with high mortality and 10 yr survival rate
has improved only from 54% to 66% during last 25 years1. The frequency of deaths due to renal
crisis significantly decreased (mainly due to effectiveness of ACE Inhibitors), from 42% to
6% of scleroderma-related deaths (p 0.001), whereas the proportion of patients with
scleroderma who died of pulmonary fibrosis increased (due to lack of significant treatment)
from 6% to 33% (p 0.001). However, presently, trials with immunosuppressive drugs including
cyclophosphamide and other targeted molecules like Bosentan and Imatinib mesylate have shown
very modest results at the best and given the risk of toxicity. The investigators have
conducted three clinical trials with PDE5 inhibitor Tadalafil in the refractory Raynaud's
phenomenon (RP) in SSc over last 3 years and had found good response in RP, healing of
digital ulcers, prevention of new digital ulcers and also observed improvement in skin
tightening, endothelial dysfunction and improvement of quality of life. The investigators
therefore hypothesize that tadalafil may have an efficacy in improving the ILD of SSc.
The investigators therefore design this double-blind, randomized, placebo-controlled trial of
oral Tadalafil (20 mg alternate day) in patients with SSc having ILD. Patients will be
randomly assigned in a 1:1 ratio to receive either Tadalafil or matched placebo and will be
followed up for 6 months. Prednisolone (if required for indications other than ILD) will be
allowed up to 10 mg/d in all patients. Patient/s requiring more than 10 mg/d of prednisolone
or equivalent dose of steroid will be excluded from the study. Patients who will fail on
therapy during the study will be excluded from the study and will be asked to choose any
therapeutic option from the rescue protocol.
Patients with FVC ≤ 70% predicted or DLCO ≤ 70 % of predicted, Evidence of ILD on HRCT will
be enrolled. The primary objective of the study will be the change in FVC (expressed as a
percentage of the predicted value) from baseline values at the end of 6-months of treatment.
The secondary objectives will be improvement in dyspnea, improvement in 6 min walk distance,
change in DLCO, change in total lung capacity, change in the disability index of the Health
Assessment Questionnaire (S HAQ), and change quality of life (SF-36), levels of NT pro-BNP
and fibrosis markers.
Phase:
Phase 3
Details
Lead Sponsor:
Sanjay Gandhi Postgraduate Institute of Medical Sciences