Vericiguat Global Study in Participants with Chronic Heart Failure: Design of the VICTOR trial

Abstract

Aims: In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF. The effect of vericiguat in patients with HFrEF without recent worsening HF remains unknown. The VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial was designed to assess the efficacy and safety of vericiguat in patients with ejection fraction ≤40% without recent worsening HF on a background of current foundational HFrEF therapy.

Methods: The primary endpoint for VICTOR is time to first event for the composite of HHF or cardiovascular death. The trial will also assess the effect of vericiguat on time to cardiovascular death, time to HHF, total HHF, and all-cause death. As an event-driven trial, at least 1080 primary events are expected, but follow-up will continue until the targeted number of at least 590 cardiovascular deaths has been reached. Approximately 6000 participants will be randomized to vericiguat or placebo.

Conclusion: VICTOR is the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational guideline-directed medical therapy, in a compensated ambulatory HF population. VICTOR will add important information to the evidence of the effects of vericiguat across the spectrum of patients with HFrEF.

Keywords: Heart failure with reduced ejection fraction; Vericiguat.

Figure 1

Cumulative incidence of hospitalization for heart failure (HHF) or cardiovascular death by recency of hospitalization in placebo arms of the EMPEROR trials. With shorter duration from recent HHF at time of enrolment, there are higher early event rates that decline with increasing duration from prior HHF. Reproduced from Ferreira et al. under the terms of the CC BY 4.0 license.

Figure 2

Hierarchical testing approach. If the primary endpoint (time to first hospitalization for heart failure [HHF] or cardiovascular [CV] death) is statistically significant, testing for secondary endpoints will proceed sequentially from (i) total HHF to (ii) time to first HHF or all‐cause mortality to (iii) time to all‐cause mortality based on achievement of statistical significance at each secondary endpoint. Testing for the individual components of the primary endpoint of (i) time to CV death and (ii) time to first HHF will be tested only if the primary endpoint is significant but will not otherwise be controlled for multiplicity.