Evaluation of the pharmacoDYNAMIC effects of riociguat in subjects with pulmonary hypertension and heart failure with preserved ejection fraction : Study protocol for a randomized controlled trial.
- Mascherbauer J Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 0190, Vienna, Austria. julia.mascherbauer@meduniwien.ac.at.
- Grünig E Centre for Pulmonary Hypertension, Thoraxclinic, University Hospital of Heidelberg, Heidelberg, Germany.
- Halank M Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.
- Hohenforst-Schmidt W Medical Clinic II, Coburg Hospital, Coburg, Germany.
- Kammerlander AA Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 0190, Vienna, Austria.
- Pretsch I Department of Cardiology, Paracelsus Medial University Salzburg, Salzburg, Austria.
- Steringer-Mascherbauer R Department of Cardiology, Public Hospital Elisabethinen Linz, Linz, Austria.
- Ulrich S Pulmonary Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Zurich, Switzerland.
- Lang IM Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 0190, Vienna, Austria.
- Wargenau M M.A.R.C.O. GmbH & Co. KG, Düsseldorf, Germany.
- Frey R , Am Eckbusch 75, 42113, Wuppertal, Germany.
- Bonderman D Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 0190, Vienna, Austria.
- 2016-09-04
Published in:
- Wiener klinische Wochenschrift. - 2016
Heart failure with preserved ejection fraction
Medical treatment
Pulmonary hypertension
Adolescent
Adult
Aged
Aged, 80 and over
Double-Blind Method
Female
Germany
Humans
Hypertension
Hypertension, Pulmonary
Male
Metabolic Clearance Rate
Middle Aged
Placebo Effect
Pyrazoles
Pyrimidines
Research Design
Stroke Volume
Vasodilator Agents
Young Adult
English
BACKGROUND
The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFPEF) resulting in substantial morbidity and mortality. So far, neither established heart failure therapies nor pulmonary vasodilators have proven to be effective for this condition. Riociguat (Adempas®, BAY 63-2521), a stimulator of soluble guanylate cyclase, is a novel pulmonary and systemic vasodilator that has been approved for the treatment of precapillary forms of PH. With regard to postcapillary PH, the DILATE-1 study was a multicenter, double-blind, randomized, placebo-controlled single-dose study in subjects with PH associated with HFPEF. Although there was no significant change in the primary outcome measure, peak decrease in mean pulmonary artery pressure with riociguat versus placebo, riociguat significantly increased stroke volume without changing heart rate, pulmonary artery wedge pressure, transpulmonary pressure gradient or pulmonary vascular resistance. The present study is designed to test the efficacy of long-term treatment with riociguat in patients with PH associated with HFPEF.
METHODS/STUDY DESIGN
The DYNAMIC study is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical phase IIb trial evaluating the efficacy, safety and kinetics of riociguat in PH-HFPEF patients. The drug will be given over 26 weeks to evaluate the effects of riociguat versus placebo. The primary efficacy variable will be the change from baseline in cardiac output at rest, measured by right heart catheter after 26 weeks of study drug treatment. Additional efficacy variables will be changes from baseline in further hemodynamic parameters, changes in left and right atrial area, right ventricular volume, as well as right ventricular ejection fraction measured by cardiac magnetic resonance imaging, and changes from baseline in World Health Organization (WHO) class and N‑terminal prohormone B‑type natriuretic peptide (NT-proBNP). The trial was registered on 25 August 2014 (EudraCT Number: 2014-003055-60; www.clinicaltrialsregister.eu ).
The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFPEF) resulting in substantial morbidity and mortality. So far, neither established heart failure therapies nor pulmonary vasodilators have proven to be effective for this condition. Riociguat (Adempas®, BAY 63-2521), a stimulator of soluble guanylate cyclase, is a novel pulmonary and systemic vasodilator that has been approved for the treatment of precapillary forms of PH. With regard to postcapillary PH, the DILATE-1 study was a multicenter, double-blind, randomized, placebo-controlled single-dose study in subjects with PH associated with HFPEF. Although there was no significant change in the primary outcome measure, peak decrease in mean pulmonary artery pressure with riociguat versus placebo, riociguat significantly increased stroke volume without changing heart rate, pulmonary artery wedge pressure, transpulmonary pressure gradient or pulmonary vascular resistance. The present study is designed to test the efficacy of long-term treatment with riociguat in patients with PH associated with HFPEF.
METHODS/STUDY DESIGN
The DYNAMIC study is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical phase IIb trial evaluating the efficacy, safety and kinetics of riociguat in PH-HFPEF patients. The drug will be given over 26 weeks to evaluate the effects of riociguat versus placebo. The primary efficacy variable will be the change from baseline in cardiac output at rest, measured by right heart catheter after 26 weeks of study drug treatment. Additional efficacy variables will be changes from baseline in further hemodynamic parameters, changes in left and right atrial area, right ventricular volume, as well as right ventricular ejection fraction measured by cardiac magnetic resonance imaging, and changes from baseline in World Health Organization (WHO) class and N‑terminal prohormone B‑type natriuretic peptide (NT-proBNP). The trial was registered on 25 August 2014 (EudraCT Number: 2014-003055-60; www.clinicaltrialsregister.eu ).
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1007/s00508-016-1068-8
- PMID 27590259
- Persistent URL
- https://sonar.ch/global/documents/97016
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