Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass
Summary
A study to evaluate levosimendan compared with placebo in reducing the composite event rate of all-cause death, perioperative MI, need for new dialysis, or use of mechanical assist (IABP, LVAD or ECMO) in subjects with reduced ejection fraction undergoing cardiac surgery on cardiopulmonary bypass (CPB).
Timeline
- Start
- 2014-07
- Primary completion
- 2016-11
- Completion
- 2016-11
Outcome
Missed primary endpoint
paper Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo PMID 28316276 ↗
paper 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). PMID 28316276 ↗
release “Tenax completed the Phase III clinical trial with levosimendan. According to the preliminary findings, the trial did not achieve its primary objectives.” orionpharma.com ↗
release “While we were disappointed that the LEVO-CTS trial did not meet its dual or quad primary endpoints, there are positive data in the results.” tenaxthera.com ↗
Publications
- Verma S, Rathwell S, Fremes S, Zheng Y, Mehta R, Lopes RD, Alexander JH, Goodman SG, Diepen SV; LEVO-CTS investigators. Associated factors and clinical outcomes in mechanical circulatory support use in patients undergoing high risk on-pump cardiac surgery: Insights from the LEVO-CTS trial. Am Heart J. 2022 Jun;248:35-41. doi: 10.1016/j.ahj.2022.02.013. Epub 2022 Mar 7.
- Mehta RH, Leimberger JD, van Diepen S, Meza J, Wang A, Jankowich R, Harrison RW, Hay D, Fremes S, Duncan A, Soltesz EG, Luber J, Park S, Argenziano M, Murphy E, Marcel R, Kalavrouziotis D, Nagpal D, Bozinovski J, Toller W, Heringlake M, Goodman SG, Levy JH, Harrington RA, Anstrom KJ, Alexander JH; LEVO-CTS Investigators. Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery. N Engl J Med. 2017 May 25;376(21):2032-2042. doi: 10.1056/NEJMoa1616218. Epub 2017 Mar 19.
- Mehta RH, Van Diepen S, Meza J, Bokesch P, Leimberger JD, Tourt-Uhlig S, Swartz M, Parrotta J, Jankowich R, Hay D, Harrison RW, Fremes S, Goodman SG, Luber J, Toller W, Heringlake M, Anstrom KJ, Levy JH, Harrington RA, Alexander JH; LEVO-CTS Investigators. Levosimendan in patients with left ventricular systolic dysfunction undergoing cardiac surgery on cardiopulmonary bypass: Rationale and study design of the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial. Am Heart J. 2016 Dec;182:62-71. doi: 10.1016/j.ahj.2016.09.001. Epub 2016 Sep 9.
- Lim JY, Deo SV, Rababa'h A, Altarabsheh SE, Cho YH, Hang D, McGraw M, Avery EG, Markowitz AH, Park SJ. Levosimendan Reduces Mortality in Adults with Left Ventricular Dysfunction Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis. J Card Surg. 2015 Jul;30(7):547-54. doi: 10.1111/jocs.12562. Epub 2015 May 19.
- Toller W, Heringlake M, Guarracino F, Algotsson L, Alvarez J, Argyriadou H, Ben-Gal T, Cerny V, Cholley B, Eremenko A, Guerrero-Orriach JL, Jarvela K, Karanovic N, Kivikko M, Lahtinen P, Lomivorotov V, Mehta RH, Music S, Pollesello P, Rex S, Riha H, Rudiger A, Salmenpera M, Szudi L, Tritapepe L, Wyncoll D, Owall A. Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion. Int J Cardiol. 2015 Apr 1;184:323-336. doi: 10.1016/j.ijcard.2015.02.022. Epub 2015 Feb 24.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Levosimendan | Other / unclassified | 0.1 ug/kg | Intravenous |