Exploring efficacy and safety of oral Pirfenidone for progressive, non-IPF lung fibrosis (RELIEF) - a randomized, double-blind, placebo-controlled, parallel group, multi-center, phase II trial

Our plain-English summary of Exploring efficacy and safety of oral Pirfenidone for progressive, non-IPF lung fibrosis (RELIEF) - a randomized, double-blind, placebo-controlled, parallel group, multi-center, phase II trial, by J. Behr, P. Neuser, A. Prasse, et al (BMC Pulmonary Medicine, 2017).

The study

• Authors: J. Behr, P. Neuser, A. Prasse, M. Kreuter, K. Rabe, C. Schade-Brittinger, J. Wagner, A. Günther
• Journal: BMC Pulmonary Medicine
• Published: 2017;17(1):122
• Type of article: Randomized trial
• Cited by: 88 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pirfenidone is currently approved in the EU for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) and offers a beneficial risk-benefit profile. However, there are several other, progressive fibrotic lung diseases, in which conventional anti-inflammatory therapy is not sufficiently effective and antifibrotic therapies may offer a novel treatment option.

Methods/design: We designed a study protocol for inclusion of patients with progressive fibrotic lung disease despite conventional anti-inflammatory therapy (EudraCT 2014-000861-32). The study population comprises patients with collagen-vascular disease-associated lung fibrosis (CVD-LF), fibrotic non-specific interstitial pneumonia (fNSIP), chronic hypersensitivity pneumonitis (cHP), and asbestos-related lung fibrosis (ALF). Disease progression needs to be proven by slope calculation of at least three Forced Vital Capacity (FVC) values obtained within 6-24 months prior to inclusion, documenting an annualized decline in percent predicted FVC of 5% (absolute) or more despite appropriate conventional therapy. Absolute change in percent predicted FVC from baseline - analyzed using a rank analysis of covariance (ANCOVA) model - will serve as efficacy-related primary study endpoint.

Discussion: There is an urgent unmet clinical need for effective therapies for patients with a progressive fibrotic lung disease other than IPF. The current study protocol is unique with respect to selecting patients with different disease entities of lung fibrosis which have, however, essential pathophysiological characteristics in common. Moreover, by selecting patients with evidence of disease progression despite conventional therapy, the protocol ensures that a cohort of interstitial lung disease (ILD) patients with a high unmet medical need is targeted and it may allow a sufficiently high event rate for evaluation of treatment responses.

Trial Registration: DRKS00009822 (registration date: January 13th 2016).

In plain English

This article is a study protocol. It describes a planned clinical trial called RELIEF and reports no treatment results. The authors designed a randomized, placebo-controlled trial comparing the drug pirfenidone (2403 mg per day) with placebo, run at centers throughout Germany. Eligible patients were aged 18 to 80 and had one of four progressive scarring (fibrotic) lung diseases other than idiopathic pulmonary fibrosis. One of these was asbestos-related lung fibrosis (ALF). For ALF, the entry criteria included asbestos-specific pleural changes (pleural plaques) on HRCT scans, reticular lung changes, a restrictive lung function pattern, and a history of asbestos exposure. Worsening had to be shown by at least three earlier lung function tests, taken over 6 to 24 months, with a yearly absolute fall of at least 5 percentage points in percent predicted forced vital capacity (FVC). The main planned outcome was the absolute change in percent predicted FVC from baseline to week 48. The authors planned 187 patients per arm. By May 3rd 2017, 74 patients had been randomized. The authors suggested that, if progressive fibrosis is the shared pathway in these diseases, pirfenidone had a good chance of slowing progression.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Study protocol for a prospective, randomized (1:1), placebo-controlled, double-blind, multi-center phase II trial (no results reported)
• Who was studied: Planned: symptomatic patients aged 18 to 80 with progressive non-IPF lung fibrosis. The four groups were collagen-vascular disease-associated lung fibrosis, fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, and asbestos-related lung fibrosis. Sites were in Germany. ALF patients needed pleural plaques on HRCT, reticular changes, a restrictive lung function pattern and a history of asbestos exposure, without extensive pleural plaques or effusion.
• Exposure: Treatment with oral pirfenidone 2403 mg per day compared with placebo. Asbestos exposure history was an entry criterion for the ALF group; no fiber types are named.
• Main results:
  • No outcome results are reported. Trial status only: by May 3rd 2017, 74 patients had been randomized at centers throughout Germany.
  • Planned, not a result: centers throughout Germany began taking part in April 2016.
  • Planned, not a result: the primary endpoint was the absolute change in percent predicted FVC from baseline to week 48.
  • Planned, not a result: entry required an absolute decline in percent predicted FVC of at least 5 percentage points per year, based on at least three earlier FVC measurements.
  • Planned, not a result: eligible patients were aged 18 to 80.
  • Planned, not a result: the sample size was 187 patients per arm.
• The authors' conclusion: The authors suggested that, if progressive fibrosis is the common pathway in these diseases, there is a good chance pirfenidone's antifibrotic effects would lessen disease progression. This is a hypothesis to be tested, not a finding.

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, Idiopathic, Pulmonary Fibrosis, Collagen, Interstitial, Pneumonitis, Disease Progression, Interstitial Lung Disease.

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