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Baseline Characteristics From a Pre-specified Interim Analysis of a Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial of Sildenafil Added to Pirfenidone in Patients With Advanced Idiopa...

J. Behr

Steven Nathan


S Harari

W Wuyts

JL Stauffer

KU Kirchgaessler

Monica Bengus

F Gilberg

AU Wells

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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1015

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.

Baseline Characteristics From a Pre-specified Interim Analysis of a Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial of Sildenafil Added to Pirfenidone in Patients With Advanced Idiopathihic Pulmonary Fibrosis and Risk of Pulmonary Hypertension

Background

Pirfenidone is one of two treatments approved for idiopathic pulmonary fibrosis (IPF). Pulmonary vascular disease and pulmonary hypertension (PH) are common in patients with advanced IPF. Although the overall results of the STEP-IPF study were inconclusive, sildenafil had beneficial effects compared with placebo in patients with right ventricular systolic dysfunction, with no safety concerns (IPFCRN 2010). Combination treatment with sildenafil and pirfenidone may address unmet needs in patients with IPF and PH. MA29957 (NCT02951429) is an ongoing study assessing the efficacy, safety and tolerability of sildenafil (20 mg TID) or placebo in patients with advanced IPF and risk of PH who are tolerating pirfenidone at a stable dose (target enrollment=176 patients). The ongoing study is being monitored by an experienced independent data monitoring committee (iDMC). We report baseline characteristics from a scheduled, blinded interim analysis performed in September 2017 for the iDMC.

Methods

Eligible patients with advanced IPF (% predicted diffusing capacity for carbon monoxide [%DLCO] ≤40%) and risk of Group 3 PH (mean pulmonary arterial pressure [mPAP] ≥20 mmHg with pulmonary arterial wedge pressure ≤15 mmHg on a previous right-heart catheterization [RHC], or intermediate/high probability Group 3 PH per the 2015 European Society of Cardiology/European Respiratory Society guidelines, i.e., peak tricuspid valve regurgitation velocity [TRV] ≥2.9 m/s). The composite primary endpoint is ≥15% decline in 6-minute walk distance (6MWD), respiratory-related non-elective hospitalization and all-cause mortality.

Results

A total of 101 patients provided signed informed consent of which 33 patients were in screening/run-in at the time of the analysis. Screening/run-in failure occurred in 20/101 patients (19.8%), mainly based on eligibility criteria related to advanced IPF and risk of PH. Forty-eight randomized patients were included in this analysis; mean age was 70.4 years, 69% were male and mean time from IPF diagnosis was 45.3 months (Table). Mean %DLCO and % forced vital capacity were 25.65% and 68.74%, respectively. Mean mPAP on RHC was 32.2 mmHg (n=6), peak TRV was 3.61 m/s and systolic pulmonary arterial pressure on ECHO was 61.8 mmHg (n=46). Mean 6MWD was 282.6 m. Updated baseline data will be presented.

Conclusions

Some baseline characteristics (e.g., age, sex, WHO class, %DLCO) were comparable to those of patients from STEP-IPF (advanced IPF; %DLCO <35%) and RISE-IIP (idiopathic interstitial pneumonia and PH confirmed by RHC). The results of this study will allow the impact of pirfenidone/sildenafil combination treatment on outcomes in patients with IPF and risk of PH to be assessed.

Baseline Characteristics From an Interim Analysis of Patients Participating in the MA29957 Study (N = 48) Compared With Those Reported in the STEP-IPF and RISE-IIP Studies1,3

 

Table 1: Baseline Characteristics From and Interim Analysis of Patients Participating in the MA29957 Study (N = 48) Compared With Those Reported in the STEP-IPF and RISE-IIP Studies