Rationale and design for a multicenter, randomized, double-blind, placebo-controlled, phase 2 study evaluating the safety and efficacy of the soluble guanylate cyclase stimulator praliciguat over 12 weeks in patients with heart failure with preserved ejection fraction (CAPACITY HFpEF)

• Published in: The American heart journal 2020-04, Vol.222, p.183-190
• Main Authors: Udelson, James E., Lewis, Gregory D., Shah, Sanjiv J., Zile, Michael R., Redfield, Margaret M., Burnett, John, Mittleman, Robert S., Profy, Albert T., Seferovic, Jelena P., Reasner, David, Konstam, Marvin A.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Age; Aged; Anaerobic threshold; Biomarkers; Blood pressure; Cardiac arrhythmia; Cardiomyopathy; Clinical trials; Congestive heart failure; Diabetes; Diabetes mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Double-blind studies; Echocardiography; Ejection fraction; Evaluation; Exercise Tolerance - physiology; Female; Follow-Up Studies; Guanosine; Guanylate cyclase; Guanylyl Cyclase C Agonists - administration & dosage; Heart failure; Heart Failure - diagnosis; Heart Failure - drug therapy; Heart Failure - physiopathology; Humans; Hypertension; Inflammation; Intolerance; Laboratories; Male; Metabolism; Middle Aged; Morbidity; Mortality; Musculoskeletal system; Nitric oxide; Objectives; Patients; Peptides; Pyrazoles - administration & dosage; Pyrimidines - administration & dosage; Quality of life; Randomization; Safety; Stimulators; Stroke Volume - physiology; Surveys and Questionnaires; Time Factors; Treatment Outcome; Trends; Ventricular Function, Left - physiology
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2020.01.009

Heart failure with preserved ejection fraction (HFpEF) is a significant cause of morbidity and mortality worldwide. Exercise intolerance is the main symptom of HFpEF and is associated with a poor quality of life and increased mortality. Currently, there are no approved medications for the treatment of HFpEF. Praliciguat (IW-1973), a novel soluble guanylate cyclase stimulator that may help restore deficient nitric oxide–soluble guanylate cyclase–cyclic guanosine 3′,5′-monophosphate signaling, is being investigated for the treatment of patients with HFpEF. CAPACITY HFpEF is a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial designed to evaluate the safety and efficacy of praliciguat over 12 weeks in approximately 184 patients with HFpEF. Eligible patients must have evidence supporting clinical HFpEF and at least 2 of the following 4 conditions associated with NO deficiency: diabetes/prediabetes, hypertension, obesity, and age >70 years. The primary efficacy end point is the change from baseline in peak VO2 by cardiopulmonary exercise test (CPET). Secondary end points include the change from baseline in 6-minute walk test distance and the change in ventilatory efficiency on CPET, as well as number of CPET responders. Other exploratory end points include changes in echocardiographic parameters, New York Heart Association functional classification, cardiac events, blood and urine biomarkers pathophysiologically relevant to heart failure, and patient-reported outcomes including Kansas City Cardiomyopathy Questionnaire. The CAPACITY HFpEF trial will provide data on short-term safety and efficacy of praliciguat on peak exercise capacity, as well as multiple secondary end points of submaximal functional capacity, patient-reported outcomes, and biomarkers.