The Efficacy and Safety of Pirfenidone in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Summary

This randomised, double-blind, placebo-controlled, phase 2 study aims to evaluate the efficacy and safety of the anti-fibrotic drug pirfenidone in the treatment of patients with heart failure and preserved left ventricular ejection fraction (HFpEF). Participants will be randomised to receive either pirfenidone or placebo, for a period of 12 months.

Timeline

Start

2017-03-02

Primary completion

2019-11-29

Completion

2020-04-29

Publications

• Background Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A, Suga M, Taguchi Y, Takahashi H, Nakata K, Sato A, Takeuchi M, Raghu G, Kudoh S, Nukiwa T; Pirfenidone Clinical Study Group in Japan. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010 Apr;35(4):821-9. doi: 10.1183/09031936.00005209. Epub 2009 Dec 8.
• Background King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. doi: 10.1056/NEJMoa1402582. Epub 2014 May 18.
• Background Van Erp C, Irwin NG, Hoey AJ. Long-term administration of pirfenidone improves cardiac function in mdx mice. Muscle Nerve. 2006 Sep;34(3):327-34. doi: 10.1002/mus.20590.
• Background Yamazaki T, Yamashita N, Izumi Y, Nakamura Y, Shiota M, Hanatani A, Shimada K, Muro T, Iwao H, Yoshiyama M. The antifibrotic agent pirfenidone inhibits angiotensin II-induced cardiac hypertrophy in mice. Hypertens Res. 2012 Jan;35(1):34-40. doi: 10.1038/hr.2011.139. Epub 2011 Aug 25.
• Background Wang Y, Wu Y, Chen J, Zhao S, Li H. Pirfenidone attenuates cardiac fibrosis in a mouse model of TAC-induced left ventricular remodeling by suppressing NLRP3 inflammasome formation. Cardiology. 2013;126(1):1-11. doi: 10.1159/000351179. Epub 2013 Jul 2.
• Lewis GA, Rosala-Hallas A, Dodd S, Schelbert EB, Williams SG, Cunnington C, McDonagh T, Miller CA. Characteristics Associated With Growth Differentiation Factor 15 in Heart Failure With Preserved Ejection Fraction and the Impact of Pirfenidone. J Am Heart Assoc. 2022 Jul 19;11(14):e024668. doi: 10.1161/JAHA.121.024668. Epub 2022 Jul 13.
• Lewis GA, Rosala-Hallas A, Dodd S, Schelbert EB, Williams SG, Cunnington C, McDonagh T, Miller CA. Impact of Myocardial Fibrosis on Cardiovascular Structure, Function and Functional Status in Heart Failure with Preserved Ejection Fraction. J Cardiovasc Transl Res. 2022 Dec;15(6):1436-1443. doi: 10.1007/s12265-022-10264-7. Epub 2022 Jul 5.
• Lewis GA, Rosala-Hallas A, Dodd S, Schelbert EB, Williams SG, Cunnington C, McDonagh T, Miller CA. Predictors of myocardial fibrosis and response to anti-fibrotic therapy in heart failure with preserved ejection fraction. Int J Cardiovasc Imaging. 2022 Jul;38(7):1569-1578. doi: 10.1007/s10554-022-02544-9. Epub 2022 Feb 9.
• Lewis GA, Dodd S, Clayton D, Bedson E, Eccleson H, Schelbert EB, Naish JH, Jimenez BD, Williams SG, Cunnington C, Ahmed FZ, Cooper A, Rajavarma Viswesvaraiah, Russell S, McDonagh T, Williamson PR, Miller CA. Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial. Nat Med. 2021 Aug;27(8):1477-1482. doi: 10.1038/s41591-021-01452-0. Epub 2021 Aug 12.
• Lewis GA, Schelbert EB, Naish JH, Bedson E, Dodd S, Eccleson H, Clayton D, Jimenez BD, McDonagh T, Williams SG, Cooper A, Cunnington C, Ahmed FZ, Viswesvaraiah R, Russell S, Neubauer S, Williamson PR, Miller CA. Pirfenidone in Heart Failure with Preserved Ejection Fraction-Rationale and Design of the PIROUETTE Trial. Cardiovasc Drugs Ther. 2019 Aug;33(4):461-470. doi: 10.1007/s10557-019-06876-y.

Drugs

Indications