Levosimendan for Cardiac Patients Undergoing Major Abdominal Cancer Surgeries

The Role of Preoperative Use of Levosimendan in Ischemic Cardiac Patients Undergoing Major Abdominal Cancer Surgeries: A Prospective Randomized Study

The objective of this pilot study is to evaluate the efficacy and safety of preoperative administration of levosimendan in patients with chronic heart failure scheduled for major abdominal cancer surgery assuming the reduction of both perioperative morbidity and mortality.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Levosimendan; Drug: Saline

Detailed Description

Cardiac complications are one of the most common causes of perioperative morbidity and mortality in patients undergoing non-cardiac surgery. Heart failure (HF) is an established risk factor for postoperative cardiac complications and mortality. The risk for postoperative mortality following major non-cardiac surgery is twice as that of patients with coronary artery disease (CAD) without HF. HF occurs in 1% to 6% of patients after major surgery, the risk being higher, between 6% and 25%, in patients with pre-existing cardiac conditions such as CAD, prior HF or valvular heart disease.

Cardiovascular disease and cancer are among the leading causes of mortality worldwide. The number of patients presenting with both diseases concomitantly is likely to increase. Cardiac patients undergoing major abdominal cancer surgeries with substantial fluid shift, blood loss and severe hemodynamic instability are at higher risk for perioperative HF.Therefore, preoperative optimization of such patients is of paramount importance. Unfortunately, guidelines for the perioperative management and preparation of such patients have not been proposed. Besides, the prophylactic use of inotropic agents for preoperative optimization of patients at high risk for HF remains controversial owing to their potential to jeopardize the myocardial oxygen supply-demand balance or to induce dysrhythmias with an assumed higher mortality.

Levosimendan is a calcium sensitizer with a positive inotropic action that has been shown to safely improve cardiac performance and hemodynamics in HF patients without increasing the myocardial oxygen demand or causing dysrrhythmias. The perioperative use of levosimendan for optimization of patients with HF has been reported in few studies with promising results, mainly for cardiac patients undergoing cardiac surgeries. However, the role of levosimendan has not been thoroughly evaluated in patients with chronic heart failure (CHF) undergoing major cancer surgery.

The purpose of this prospective study is to evaluate the safety and efficacy of preoperative administration of levosimendan in patients with CHF scheduled for major abdominal cancer surgery.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11796
    • Department of Anesthesia and Pain medicine.National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients suffering from CHF with left ventricular ejection fraction < 35%, scheduled for major abdominal cancer surgery were eligible.
• Aged 18 to 75 years.

Exclusion criteria were :

• restrictive or obstructive cardiomyopathy.
• severe cardiac valvular disease.
• history of atrial fibrillation, ventricular tachycardia or fibrillation.
• resting systolic arterial pressure <80 mmHg.
• second or third degree atrioventricular block.
• Child-Pugh class C liver cirrhosis.
• severe renal failure (defined as creatinine clearance < 30 ml/min).
• Immediate postoperative complications such as surgical re-exploration for bleeding or suspected leak.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: levosimendan; Levosimendan was prepared in a concentration of 25 µg/ml and infusion was commenced at a rate of 0.1 µg/kg/minute without loading and continued for 24 hours before surgery.The dose was doubled if an increase of > 20 mmHg in systolic blood pressure (SBP) could not be obtained within 2 hours after starting the infusion. Indications for dose reduction were the development of hypotension (SBP < 80 mmHg) or tachycardia (heart rate > 120 beats/min) persisting for more than 10 minute or (premature beats in a frequency exceeding 6/min or occurrence of a significant arrhythmia occurring in runs). The infusion medication would be discontinued should such occurrences persist despite dose reduction.	Drug: Levosimendan; Preoperative 24 hours infusion of levosimendan for chronic heart failure patients prior to major abdominal cancer surgeries.; Other Names: drug group
Active Comparator: control; In the control group ,an identical saline infusion regimen was employed instead of levosimendan . Both patient and care giver were blinded for the study.	Drug: Saline; Preoperative 24 hours infusion of normal saline for chronic heart failure patients prior to major abdominal cancer surgeries.; Other Names: control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in mechanical ventilation	The total duration of postoperative ventilation in days	Baseline and after two weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Ejection fraction	The improvement in the ejection fraction in percentage.	Baseline and after one week postoperative
Changes in cardiac index	The improvement in Cardiac index (Liters/minute/square meter)	Baseline and after one week postoperative
Changes in Stroke volume index	The improvement in stroke volume index(milliliters/square meter)	Baseline and after one week postoperative
Patient total hospital length of stay	Total hospital length of stay in days.	Baseline and after two weeks postoperative

Collaborators and Investigators

• Sponsor: National Cancer Institute, Egypt
• Investigators: Principal Investigator: Ehab H Shaker, MD, National Cancer Institute- Cairo University

Publications and helpful links

Helpful Links

• Preconditioning effects of levosimendan in coronary artery bypass grafting-a pilot study.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): April 23, 2018

Study Registration Dates

• First Submitted: May 10, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 14, 2018

Study Record Updates

• Last Update Posted (Actual): June 14, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: Ehab-Raafat.Levo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: the results ,conclusion and final recommendation can be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No