Home > Cardiology > HFA 2022 > Phase 1/2 Trials > SERENADE: Macitentan fails in HFpEF plus PAH

SERENADE: Macitentan fails in HFpEF plus PAH

Presented by
Prof. Adriaan Voors , University of Groningen, the Netherlands
Conference
HFA 2022
Trial
Phase 2, SERENADE
Doi
https://doi.org/10.55788/596ea84f
Macitentan did not provide benefits for patients with heart failure (HF) with preserved ejection fraction (HFpEF) plus pulmonary arterial hypertension (PAH), according to the late-breaking results of the SERENADE trial.

“Macitentan is an orally active, non-peptide, potent, dual endothelin receptor antagonist (ERA), approved for the treatment of PAH,” said Prof. Adriaan Voors (University of Groningen, the Netherlands) [1]. The multicentre, phase 2b SERENADE trial (NCT03153111) originally aimed to enrol 300 patients with HFpEF and pulmonary vascular disease to be randomised 1:1 to placebo or macitentan for 52 weeks after a 4-week placebo run-in and a 5-week macitentan run-in. The run-in periods aimed to identify and exclude participants who were susceptible to developing fluid retention. The recruitment stopped early due to slow enrolment, and the double-blind phase of the trial was cut down to 24 weeks. Notably, approximately 12% and 30% of the participants dropped out during the placebo and macitentan run-in periods, respectively. The main reason for treatment failure was, the exceeding of fluid retention restrictions the study sought to avoid. In the end, only 71 participants in each arm could be analysed for the primary endpoint, which was the change in NT-proBNP from baseline.

After 24 weeks, the study groups showed no difference regarding the primary endpoint (geometric mean ratio 1.02; P=0.79). Similarly, the time to worsening HF was similar in the placebo arm and macitentan arm (HR 1.48; P=0.24). Furthermore, 88.7% and 85.9% of the participants in the macitentan and placebo groups displayed at least 1 adverse event. Fluid retention was still more frequently observed in the active arm than in the placebo arm (22.5% vs 14.1%).

“Despite a novel enrichment trial designed to target PAH associated with HFpEF and exclude treatment-related fluid retention, macitentan neither lowered NT-proBNP nor improved heart failure outcomes in patients with HFpEF and pulmonary vascular disease,” concluded Prof. Voors.

  1. Voors A, et al. SERENADE: Macitentan in heart failure with preSERved ejEction fractioN and pulmonAry vascular DiseasE. LBT Pharmacotherapy, Heart Failure 2022, 21–24 May, Madrid, Spain.

 

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