Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) - 12/05/18
, Javed Butler, MD c, Emmanuel Fombu, MD d, Alan Maisel, MD e, Kevin McCague, MA d, Ileana L. Piña, MD f, Margaret F. Prescott, PhD d, Jerome B. Riebman, MD d, Scott Solomon, MD gAbstract |
Background |
Sacubitril/valsartan is an angiotensin receptor–neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use.
Methods |
This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy. Approximately 830 patients with HF with reduced ejection fraction will be initiated and titrated on sacubitril/valsartan according to United States prescribing information. Primary efficacy end points include the changes in N-terminal pro–B-type natriuretic peptide concentrations and cardiac remodeling from baseline to 1 year. Secondary end points include changes in concentrations of N-terminal pro–B-type natriuretic peptide and remodeling to 6 months, and changes in patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire-23 from baseline to 1 year. In addition, several other relevant biomarkers will be measured. Biomarker changes relative to the number of cardiovascular events in 12 months will also be assessed as exploratory end points.
Conclusions |
Results from the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) will help establish a mechanistic understanding of angiotensin receptor–neprilysin inhibitor therapeutic benefits and provide clinicians with clarity on how to interpret information on biomarkers during treatment (PROVE-HF ClinicalTrials.gov identifier: NCT02887183).
Le texte complet de cet article est disponible en PDF.Graphical abstract |
X = vital status/events (CV death, HF hospitalization, worsening HF), physical examination, blood sampling, urine sampling, HF symptom assessment, KCCQ-23.
*Standard HF therapy is continued throughout the study. †At day 45, KCCQ-23 was not administered.
At selected sites, samples will be collected in protease inhibitor tubes at each timepoint (n = 180).
Plan
| RCT# NCT02887183 |
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| Conflicts of interest James L. Januzzi: grant support from Roche Diagnostics, Siemens, Cleveland Heart Labs, and Prevencio, consulting income from Roche Diagnostics, Abbott, Phillips, and Novartis; and participates in clinical end point committees/data safety monitoring boards for AbbVie, Bayer, Pfizer, Novartis, Amgen, Janssen, and Boehringer-Ingelheim. Javed Butler: consultant for Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, CVRx, Medtronic, Novartis, Relypsa, and ZS Pharma. Emmanuel Fombu: employee, Novartis Pharmaceuticals Corporation. Alan Maisel: consultant for Critical Diagnostics and Alere; research support from Norvartis and Roche. Kevin McCague: employee, Novartis Pharmaceuticals Corporation. Ileana L. Piña: nothing to declare. Margaret F. Prescott: employee, Novartis Pharmaceuticals Corporation. Jerome B. Riebman: employee, Novartis Pharmaceuticals Corporation. Scott Solomon: consultant for Novartis; research grant from Novartis through academic institution. All authors have approved the final article for submission to the journal. |
Vol 199
P. 130-136 - mai 2018 Retour au numéro
Article précédent
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