Levosimendan Trial – Phase 3
Levosimendan is under development in North America for reduction in morbidity and mortality of cardiac surgery patients at risk of low cardiac output syndrome (LCOS).
The FDA has granted Fast Track status for levosimendan and has agreed to our Phase 3 clinical trial protocol under a Special Protocol Assessment (SPA). The FDA has provided guidance that a single successful trial will be sufficient to support approval of levosimendan in this indication.
The Phase 3 clinical trial will study if levosimendan administered before and during surgery will reduce the incidence of morbidity and mortality in cardiac surgery patients at risk. There is substantial scientific evidence for the use of levosimendan in cardiovascular surgery, including data from over 30 published clinical trials.
Additional information about the trail can be found at https://clinicaltrials.gov/ct2/show/NCT02025621.
Novel Product /
Levosimendan is a novel, first-in-class calcium sensitizer/K-ATP activator that provides:
- oxygen sparing improvements in myocardial contractility
- reductions in afterload
- potential cardioprotective effects
Currently there are no drugs indicated for the prevention or the treatment of LCOS.
The FDA has granted fast track status for the “development of levosimendan to reduce morbidity and mortality in cardiac surgery patients at risk for developing low cardiac output syndrome.”
Low LVEF cardiac surgery patients represent a high risk population who experience a higher incidence of LCOS and worse outcomes.
Levosimendan has the potential to improve outcomes in these high risk patients.
FDA Fast Track Status /
The FDA has granted fast track status based on the drug’s potential to fill a serious unmet medical need, and has agreed to the Phase 3 trial protocol under a Special Protocol Assessment (SPA). FDA has provided guidance that a single successful trial will be sufficient to support approval of levosimendan in the U.S.
The trial design is based on extensive review of the scientific literature including more than 30 cardiac surgery studies published in peer-reviewed medical journals. Several meta-analyses indicate levosimendan may substantially reduce morbidity and mortality in cardiac surgery patients who are at risk of Low Cardiac Output Syndrome (LCOS).
Levosimendan is approved outside the U.S. to treat acute decompensated heart failure in more than 60 countries and has been used to treat more than 1,000,000 patients. Levosimendan is commonly used in high risk cardiac surgery patients, despite lacking an approved indication.
More About Levosimendan
Levosimendan is being developed by Tenax Therapeutics, Inc. for the U.S. and Canadian market. Tenax licensed levosimendan from Orion Pharma in Espoo, Finland. Levosimendan is a calcium sensitizer/K-ATP activator that works through a unique triple MOA:
- Increased cardiac contractility by calcium sensitization of troponin C, resulting in increased cardiac output that is not associated with substantial increases in oxygen demand.
- Opening of potassium channels in the vasculature smooth muscle, resulting in vasodilatory effect on all vascular beds.
- Opening of mitochondrial potassium channels in cardiomyocytes, resulting in a cardioprotective effect during periods of myocardial ischemia.
More about the LEVO-CTS Study
- Tenax and the Duke Clinical Research Institute (DCRI) are actively recruiting cardiac surgeons and cardiac anesthesiologists to act as investigators in the LEVO-CTS trial.
- The study’s primary goal is to demonstrate reduced morbidity and mortality in at risk cardiac surgery patients.
- The study has enrolled over 880 patients with a coronary artery bypass graft or mitral valve surgery who are at risk of LCOS.
- Approximately 60 sites will be included in the trial.
- Lead investigators are John Alexander, MD and Rajendra Mehta, MD, DCRI, Durham, NC.
Steering Committee Members
- John Alexander, MD, DCRI, Duke Medicine
- Robert Harrington, MD, Stanford University
- John Luber, MD, Franciscan Health System
- Wolfgang Toller, MD, University of Graz, Austria
- Matthias Heringlake, MD, University of Lübeck, Germany
- Jerrold H. Levy, MD, Duke University Medicine
- Kevin Anstrom, PhD, DCRI, Duke Medicine
- John Kelley, CEO, Tenax Therapeutics, Inc.