Rationale and Design of the Phase 2B Clinical Trials to Study the Effects of the Partial Adenosine A1-Receptor Agonist Neladenoson Bialanate in Patients with Chronic Heart Failure with Reduced (Pantheon) and Preserved (Panache) Ejection Fraction
Year: 2018
Type: article
Study design: Study Protocol
Abstract: Despite major advances in the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF), morbidity and mortality associated with the condition remain high, suggesting the need for additional treatment options, particularly haemodynamically neutral treatments that do not alter blood pressure, heart rate, or renal function. HF with preserved ejection fraction (HFpEF) is also associated with high morbidity and mortality and adequate treatment options are limited; thus there is a critical unmet need for the development of novel therapies for HFpEF. Chronic HFrEF and HFpEF are both systemic disorders that affect not only the heart but several other tissues and organs including skeletal muscle, leading to exercise intolerance and dyspnoea. Partial adenosine A1-receptor agonists represent a novel potential therapy for HF regardless of underlying ejection fraction given their minimal effect on heart rate and blood pressure, and preclinical data demonstrate several possible beneficial mechanisms, including improved mitochondrial function and sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, enhanced energy substrate utilization, reverse ventricular remodelling, and anti-ischemic, cardioprotective properties. However, data on this class of drugs in humans are scarce, and the optimal dose of the partial adenosine A1 receptor, neladenoson bialanate, has not been defined. Here we describe the design and rationale of two randomized, double-blind, placebo-controlled, parallel-group, dose-finding phase 2b trials, PANTHEON (HFrEF) and PANACHE (HFpEF), that will advance our understanding of the potential benefit and optimal dose of neladenoson bialanate and provide critical information for the planning of future phase 3 trials.
DOI: 10.1002/ejhf.1295
Institutions: University Medical Center Groningen, University of Groningen, Northwestern University, Leiden University Medical Center, University of Mississippi Medical Center, University of Mississippi, Duke University, Wake Forest University Health Sciences, Wake Forest University, British Heart Foundation, University of Glasgow, Bayer (Germany), Brigham and Women's Hospital
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Bayer
OpenAlex ID: W2889970908