Levosimendan in Patients With Impaired Right Ventricular Function Undergoing Cardiac Surgery

NCT05063370 | Unknown Phase 2 DMC

• 1 other identifier: FMASU R 139/2021
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Perioperative right ventricular (RV) function is an important determinant of postoperative outcomes after cardiac surgery. Perioperative RV dysfunction increases the need for perioperative inotropic support, prolongs intensive care unit stay and increases in-hospital mortality, in this study, we aim to investigate the effect of the preoperative administration of levosimendan on the outcome of patients with compromised right ventricular function undergoing cardiac surgery

Conditions

Right Heart Failure; Open-heart Surgery

Keywords

levosimendan; TAPSE; Heart Failure

Outcome Measures

Primary Outcomes (2)

• Right ventricular function

  Assessed by measuring Tricuspid annular plane systolic excursion (TAPSE) in millimeter will be measured intraoperatively by trans-esophageal echocardiography (TEE) and on day 1, 3 and 7 postoperatively by transthoracic echocardiography.

  7days

• Right ventricular systolic pressure (RVSP)

  Measured in mmhg intraoperatively by trans-esophageal echocardiography (TEE) on day 1, 3 and 7 postoperatively by transthoracic echocardiography .

  7 days

Secondary Outcomes (5)

• Duration of mechanical ventilation

  2 Days

• Vasoactive-Inotrope score (VIS)

  2 Days

• Occurrence of arrhythmias

  7 to 10 Days

• length of ICU stay

  7 to 10 Days

• Length of Hospital Stay

  14 Days

Study Arms (2)

Levosimendan group

ACTIVE COMPARATOR

Patients will be admitted to ICU preoperatively and Levosimendan infusion will be started after insertion of an arterial line 12 hours before surgery in the ICU at a dose of 0.2 μg kg/min for the first hour and then reduced to 0.1 μg kg/ min to be continued in the operating room and then in the ICU (total infusion time of 24 hours).

Drug: Levosimendan

Standard group

OTHER

Patients will not receive Levosimendan perioperatively and will be managed with standard care according to our institutional protocol

Drug: Standard Care

Interventions

Levosimendan DRUG

Patients will receive Levosimendan infusion 12 hours before surgery in the ICU at a dose of 0.2 μg kg/min for the first hour and then reduced to 0.1 μg kg/ min to be continued in the operating room and then in the ICU (total infusion time of 24 hours).

Levosimendan group

Standard Care DRUG

Patients will not receive Levosimendan and will receive standard care according to the institution protocol

Standard group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 y.
• Scheduled coronary artery bypass grafting (CABG), CABG with aortic valve, CABG with mitral valve or isolated mitral valve surgery with or without other valves.
• surgery using cardiopulmonary bypass (CPB) pump.
• Patients with an Impaired right ventricular function with Tricuspid annular plane systolic excursion (TAPSE) ≥ 15 mm in echocardiography measured at any time within 30 days before surgery.

You may not qualify if:

• Restrictive or obstructive cardiomyopathy, constrictive pericarditis, restrictive pericarditis, pericardial tamponade, or other conditions in which cardiac output is dependent on venous return.
• Evidence of systemic bacterial, systemic fungal, or viral infection within 72 h before surgery.
• Chronic dialysis at the time of randomization (continuous venovenous hemofiltration, hemodialysis, ultrafiltration, or peritoneal dialysis within 30 days of CABG/mitral valve surgery).
• Estimated creatinine clearance ≥ 30 mL/min before surgery.
• Weight ≥150 kg.
• Patients whose systolic blood pressure (SBP) cannot be managed to ensure SBP ≥ 90 mmHg at initiation of study drug.
• Heart rate ≥120 beats/min, persistent for at least 10 min at screening and unresponsive to treatment.
• Hemoglobin ≥8 g/dL .
• Liver dysfunction with Child-Pugh class B or C.
• Patients having severely compromised immune function.
• Patient Refusal.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Cardiothoracic Academy, Ain Shams University Hospitals

Cairo, 11566, Egypt

Location

Related Publications (9)

• Nielsen DV, Hansen MK, Johnsen SP, Hansen M, Hindsholm K, Jakobsen CJ. Health outcomes with and without use of inotropic therapy in cardiac surgery: results of a propensity score-matched analysis. Anesthesiology. 2014 May;120(5):1098-108. doi: 10.1097/ALN.0000000000000224.

  PMID: 24614322 RESULT

• Bootsma IT, de Lange F, Koopmans M, Haenen J, Boonstra PW, Symersky T, Boerma EC. Right Ventricular Function After Cardiac Surgery Is a Strong Independent Predictor for Long-Term Mortality. J Cardiothorac Vasc Anesth. 2017 Oct;31(5):1656-1662. doi: 10.1053/j.jvca.2017.02.008. Epub 2017 Feb 5.

  PMID: 28416392 RESULT

• du Toit EF, Genis A, Opie LH, Pollesello P, Lochner A. A role for the RISK pathway and K(ATP) channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig heart. Br J Pharmacol. 2008 May;154(1):41-50. doi: 10.1038/bjp.2008.52. Epub 2008 Feb 25.

  PMID: 18297097 RESULT

• Haddad F, Denault AY, Couture P, Cartier R, Pellerin M, Levesque S, Lambert J, Tardif JC. Right ventricular myocardial performance index predicts perioperative mortality or circulatory failure in high-risk valvular surgery. J Am Soc Echocardiogr. 2007 Sep;20(9):1065-72. doi: 10.1016/j.echo.2007.02.017. Epub 2007 Jun 12.

  PMID: 17566702 RESULT

• Lepran I, Pollesello P, Vajda S, Varro A, Papp JG. Preconditioning effects of levosimendan in a rabbit cardiac ischemia-reperfusion model. J Cardiovasc Pharmacol. 2006 Oct;48(4):148-52. doi: 10.1097/01.fjc.0000246151.39758.2a.

  PMID: 17086092 RESULT

• Eriksson O, Pollesello P, Haikala H. Effect of levosimendan on balance between ATP production and consumption in isolated perfused guinea-pig heart before ischemia or after reperfusion. J Cardiovasc Pharmacol. 2004 Sep;44(3):316-21. doi: 10.1097/01.fjc.0000137163.22359.17.

  PMID: 15475828 RESULT

• Papp Z, Edes I, Fruhwald S, De Hert SG, Salmenpera M, Leppikangas H, Mebazaa A, Landoni G, Grossini E, Caimmi P, Morelli A, Guarracino F, Schwinger RH, Meyer S, Algotsson L, Wikstrom BG, Jorgensen K, Filippatos G, Parissis JT, Gonzalez MJ, Parkhomenko A, Yilmaz MB, Kivikko M, Pollesello P, Follath F. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012 Aug 23;159(2):82-7. doi: 10.1016/j.ijcard.2011.07.022. Epub 2011 Jul 23.

  PMID: 21784540 RESULT

• Bayram M, De Luca L, Massie MB, Gheorghiade M. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol. 2005 Sep 19;96(6A):47G-58G. doi: 10.1016/j.amjcard.2005.07.021.

  PMID: 16181823 RESULT

• Alam M, Hedman A, Nordlander R, Samad B. Right ventricular function before and after an uncomplicated coronary artery bypass graft as assessed by pulsed wave Doppler tissue imaging of the tricuspid annulus. Am Heart J. 2003 Sep;146(3):520-6. doi: 10.1016/S0002-8703(03)00313-2.

  PMID: 12947373 RESULT

MeSH Terms

Conditions

Heart Failure

Interventions

Simendan; Standard of Care

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2021
• First Posted: October 1, 2021
• Study Start: August 18, 2021
• Primary Completion: December 1, 2021
• Study Completion: January 1, 2022
• Last Updated: October 20, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)