Pirfenidone for Restrictive Chronic Lung Allograft Dysfunction
Status:
Active, not recruiting
Trial end date:
2021-10-31
Target enrollment:
Participant gender:
Summary
Despite advances in lung transplantation, the median survival remains only 55% at 5 years.
The main limitation to long term survival is the development of chronic lung allograft
dysfunction. In approximately 30% of cases, chronic lung allograft dysfunction has a
restrictive phenotype (RCLAD) characterized by fibrosis with rapid progression to respiratory
failure. Approximately 60% of patients with RCLAD die within one year, as currently there are
no therapies available.
RCLAD, like Idiopathic Pulmonary Fibrosis (IPF), is characterized by fibroblast
proliferation, extracellular matrix deposition, and architectural distortion leading to
progressive lung scarring and death. Given their similarities, there is keen interest in the
international transplant community to investigate whether the anti-fibrotic drug pirfenidone
can slow the progression of RCLAD as it does of IPF. Pirfenidone has been proved to be safe
and effective in patients with IPF, and is approved by the Food and Drug Administration.
This protocol will evaluate the safety and tolerability of pirfenidone in lung transplant
recipients with RCLAD. Transplant recipients take carefully adjusted immunosuppressive
medications for life to prevent rejection of the allograft. Current literature suggests the
dose of tacrolimus, the main anti-rejection drug, may need to be adjusted when taken in
combination with pirfenidone. The investigators will assess the side effects of pirfenidone
in combination with the immunosuppressive regimen and determine the magnitude of the
adjustment in tacrolimus dose. The results of this pilot study will provide the foundation
for a multicenter randomized control trial to evaluate the efficacy of pirfenidone in slowing
the progression of RCLAD.