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Seismic launches global Phase III trial of istaroxime in cardiogenic shock

Seismic launches global Phase III trial of istaroxime in cardiogenic shock

Durham, North Carolina-based Seismic Pharmaceuticals has launched a global Phase III trial of istaroxime in cardiogenic shock, a life-threatening condition with no US FDA-approved pharmacological therapy.

The RESCUE HF-CS study is expected to enroll approximately 600 patients across the US, Europe, and South America. The randomized, double-blind trial is evaluating istaroxime plus standard care against placebo plus standard care in patients with SCAI Stage B or C cardiogenic shock due to acute heart failure.

Istaroxime is an intravenous therapy with a dual mechanism designed to improve both cardiac contraction and relaxation. It inhibits Na+/K+-ATPase to increase contractility while activating SERCA2a, a calcium pump involved in cardiac relaxation. The mechanism differs from conventional inotropes such as dobutamine and milrinone, which act through cAMP-dependent pathways and can increase arrhythmia risk.

The Phase III program builds on four completed Phase II trials in which more than 340 patients received istaroxime. These included the SEISMiC studies in patients with acute heart failure and pre-cardiogenic shock, as well as SEISMiC-C, which evaluated the drug in SCAI Stage C cardiogenic shock. Earlier studies, including IGNITE, established its hemodynamic activity in acute decompensated heart failure.

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Istaroxime was previously developed by Windtree Therapeutics before Seismic acquired the program following its formation in March 2026 with backing from Panacea Capital. Seismic was established to advance Windtree's clinical-stage heart failure portfolio and has said it aims to complete the first Phase III study in support of potential registration in China by 2027.

Cardiogenic shock is currently managed with off-label vasopressors and inotropes, alongside mechanical circulatory support in selected patients. Seismic is positioning istaroxime as a potential first pharmacological therapy specifically approved for the condition.


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