Sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: A Phase IIb, randomised, double-blind, placebo-controlled study - Rationale and study design.

BACKGROUND: Pulmonary hypertension (PH) is commonly observed in patients with advanced idiopathic pulmonary fibrosis (IPF). Despite the availability of therapies for both IPF and PH, none are approved for PH treatment in the context of significant pulmonary disease. This study will investigate the use of sildenafil added to pirfenidone in patients with advanced IPF and risk of PH, who represent a group with a high unmet medical need. METHODS: This Phase IIb, randomised, double-blind, placebo-controlled trial is actively enrolling patients and will study the efficacy, safety and tolerability of sildenafil or placebo in patients with advanced IPF and intermediate or high probability of Group 3 PH who are receiving a stable dose of pirfenidone. Patients with advanced IPF (diffusing capacity for carbon monoxide ≤40% predicted) and risk of Group 3 PH (defined as mean pulmonary arterial pressure ≥20 mm Hg with pulmonary arterial wedge pressure ≤15 mm Hg on a previous right-heart catheterisation [RHC], or intermediate/high probability of Group 3 PH as defined by the 2015 European Society of Cardiology/European Respiratory Society guidelines) are eligible. In the absence of a previous RHC, patients with an echocardiogram showing a peak tricuspid valve regurgitation velocity ≥2.9 m/s can enrol if all other criteria are met. The primary efficacy endpoint is the proportion of patients with disease progression over a 52-week treatment period. Safety will be evaluated descriptively. DISCUSSION: Combination treatment with sildenafil and pirfenidone may warrant investigation of the treatment of patients with advanced IPF and pulmonary vascular involvement leading to PH.