Design of PROGRESSION-IPF: A pragmatic, open-label, randomized trial of patients with progressive disease in idiopathic pulmonary fibrosis.

BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease with poor prognosis. Although antifibrotic therapies such as pirfenidone and nintedanib slow lung function decline, optimal management of patients with progression despite treatment remains undefined. Evidence-based guidance for continuation, switching, or combination of antifibrotics is lacking.

OBJECTIVE

The PROGRESSION-IPF trial evaluates the efficacy and safety of combination therapy with pirfenidone and nintedanib compared with switching to the alternative antifibrotic or continuing current monotherapy in patients with progressive IPF.

METHODS

This pragmatic, multicenter, randomized, open-label trial will enroll 378 patients aged ≥50 years with IPF showing progression within the preceding 12 ± 6 months despite antifibrotic therapy. Participants will be randomized 1:1:1 to combination therapy, switch monotherapy, or continuation of current monotherapy. The primary endpoint is the slope of forced vital capacity (FVC) decline over 24 weeks. Secondary endpoints include tolerability, time to treatment failure or discontinuation, hospitalization-free survival, fibrosis progression on imaging, initiation of oxygen, acute exacerbations, and patient-reported outcomes. FVC measurements are reviewed by a blinded Lung Function Central Review Committee. Exploratory analyses include serum CA-125 as a potential biomarker of disease progression. Statistical analyses will use linear mixed models for the primary endpoint and appropriate tests for secondary outcomes.

ETHICS AND DISSEMINATION: The study was approved by the French ethics committee (CPP Est-2) and the national health authority (ANSM). An independent Data and Safety Monitoring Board ensures patient safety. PROGRESSION-IPF may inform guidelines and define a practical standard for managing progressive IPF.