James E Udelson1, Gregory D Lewis2, Sanjiv J Shah3, Michael R Zile4, Margaret M Redfield5, John Burnett5, Robert S Mittleman6, Albert T Profy6, Jelena P Seferovic6, David Reasner7, Marvin A Konstam8. 1. Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Boston, MA. Electronic address: JUdelson@tuftsmedicalcenter.org. 2. Massachusetts General Hospital and Harvard Medical School, Boston, MA. 3. Northwestern University Feinberg School of Medicine, Chicago, IL. 4. Medical University of South Carolina and the RHJ Department of Veterans Affairs Medical Center, Charleston, SC. 5. Mayo Clinic, Rochester, MN. 6. Cyclerion Therapeutics, Cambridge, MA. 7. Ironwood Pharmaceuticals, Cambridge, MA. 8. Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Boston, MA.
Abstract
BACKGROUND: 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. METHODS: 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. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: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-cyclicguanosine 3',5'-monophosphate signaling, is being investigated for the treatment of patients with HFpEF. METHODS: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. CONCLUSIONS: 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.
Authors: James E Udelson; Gregory D Lewis; Sanjiv J Shah; Michael R Zile; Margaret M Redfield; John Burnett; John Parker; Jelena P Seferovic; Phebe Wilson; Robert S Mittleman; Albert T Profy; Marvin A Konstam Journal: JAMA Date: 2020-10-20 Impact factor: 56.272