Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction: a phase IIb, randomized, double-blind, placebo-controlled trial

PANTHEON Investigators, Voors, A. A., Bax, J. J., Hernandez, A. F., Wirtz, A. B., Pap, A. F., Ferreira, A. C., Senni, M., van der Laan, M. & Butler, J., Nov-2019, In : European Journal of Heart Failure. 21, 11, p. 1426-1433 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • PANTHEON Investigators
  • Adriaan A. Voors
  • Jeroen J. Bax
  • Adrian F. Hernandez
  • Antonieta B. Wirtz
  • Akos F. Pap
  • Anna C. Ferreira
  • Michele Senni
  • Michael van der Laan
  • Javed Butler

Aims Neladenoson bialanate is a partial adenosine A1 receptor agonist with demonstrated beneficial effects on cardiac function in animal models. We aimed to assess the dose-response effect of neladenoson bialanate on cardiac structure and function, clinical outcome, and safety in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results PANTHEON was a dose-finding, phase IIb, randomized, double-blind, placebo-controlled trial conducted in 92 centres in 11 countries including 462 patients with chronic HFrEF, randomized to once daily oral dose of neladenoson bialanate (5, 10, 20, 30, and 40 mg) or placebo. The primary endpoints were change from baseline to 20 weeks in left ventricular ejection fraction (LVEF) (echocardiography) and in N-terminal pro-B-type natriuretic peptide (NT-proBNP). Mean age of the patients was 67 years, 17% were female, mean LVEF was 28%, mean NT-proBNP was 2085 ng/L. After 20 weeks of treatment, there was no dose-effect of neladenoson bialanate on changes in NT-proBNP or LVEF (primary endpoints). No effect of neladenoson bialanate was found on left ventricular volumes, high-sensitivity troponin T, or cardiovascular mortality, HF hospitalization, and urgent visits for HF (secondary endpoints). There was a dose-dependent increase in creatinine and cystatin C, and a dose-dependent decrease in estimated glomerular filtration rate and heart rate. Conclusions In patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose-dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose-dependent decrease in renal function. Clinical Trial Registration: identifier NCT02992288.

Original languageEnglish
Pages (from-to)1426-1433
Number of pages8
JournalEuropean Journal of Heart Failure
Issue number11
Publication statusPublished - Nov-2019


  • Heart failure, Adenosine, Partial adenosine A1 agonist, Cardiac contractility, Renal function, ADENOSINE, ANTAGONIST

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