Levosimendan, an investigational therapy for pulmonary hypertension associated with heart failure and preserved ejection fraction (PH-HFpEF), was found to improve workings of the kidneys in PH-HFpEF patients with kidney impairment in a Phase 3 clinical trial.
Findings from the study, “Differential effects of levosimendan and dobutamine on glomerular filtration rate in patients with heart failure and renal impairment: a randomized double-blind controlled trial,” were published in the Journal of the American Heart Association.
The kidneys ability to work well is often impaired in heart failure patients, a comorbidity known as cardiorenal syndrome. This syndrome can affect people with PH-HFpEF, a type of PH related to left heart disease.
Inotrope medications, which have the ability to alter the force of muscular contractions, have been used as therapies for heart failure patients with decompensated heart function and compromised blood flow in vital organs, including the kidneys.
Levosimendan, being developed by Tenax Therapeutics, belongs to this class of medicines. It is a calcium sensitizer and potassium channel opener (K-ATP activator) that can increase heart contractility and vasodilation. It is approved in more than 60 countries to treat severe chronic heart failure, but not in the U.S. In Europe, levosimendan is marketed as Simdax.
To compare the effects of two inotrope medicines, levosimendan and Dobutrex (dobutamine; an approved therapy for heart failure), on kidney function in patients with chronic heart failure and signs of cardiorenal syndrome, researchers at Sahlgrenska University Hospital in Gothenburg, Sweden, conducted a Phase 3 clinical trial (NCT02133105).
The study enrolled 32 patients given moderate infusion doses of levosimendan (0.1 micrograms per kilogram of body mass per minute) and dobutamine (7.5 micrograms per kilogram per minute), for 75 minutes.
Kidney function was evaluated via renal blood flow (RBF), a measure of how much blood is delivered to the kidneys per unit time, and by glomerular filtration rate (GFR), or how much blood passes through the glomeruli, the kidney structures responsible for blood filtration.
Results demonstrated that both medicines induced vasodilation (opening of the blood vessels) in the kidneys, and increased RBF to a similar extent — 22% for levosimendan and 26% for dobutamine.
But only levosimendan was seen to increase GFR (by 22%); these levels remained unchanged in the dobutamine group.
“In patients with chronic heart failure and renal impairment, levosimendan increases glomerular filtration rate to a greater extent than dobutamine and thus may be the preferred inotropic agent for treating patients with the cardiorenal syndrome,” the researchers concluded.
Anthony DiTonno, chief executive officer of Tenax Therapeutics, said in a press release: “The results of this new study are encouraging. These findings are consistent with earlier studies and potentially very relevant to our current levosimendan clinical development plans in PH-HFpEF patients.
“Heart failure patients commonly suffer from renal dysfunction and should benefit from the unique renal protective benefits that levosimendan appears to provide heart failure patients, including PH-HFpEF patients with renal impairment,” DiTonno added.
Tenax Therapeutics recently launched a Phase 2 trial (NCT03541603) to test the safety and efficacy of levosimendan in improving heart function in PH-HFpEF patients. This six-week study is expected to soon begin enrolling participants; more information is available here.