The Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement

Heart Failure Clinical Trial

Official title:

A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04573049
• Other study ID #: 2020-1357
• Status: Recruiting
• Phase: Phase 4
• Start date: September 1, 2020
• Est. completion date: December 30, 2022

Study information

• Verified date: September 2020
• Source: China National Center for Cardiovascular Diseases
• Contact: Jianhui Wang, MD
• Phone: 010-88398082
• Email: stewenwang[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to evaluate the effectiveness and safety of levosimendan compared with placebo in subjects with severe aortic stenosis and heart failure undergoing transcatheter aortic valve replacement

Description:

The number of subjects undergoing transcatheter aortic valve replacement to treat aortic stenosis have been increasing in recent decades. Levosimendan, an innovative inotrope, is powerfully evidenced to have the function to improve cardiac output and hemodynamic parameters. However, there is no specified study concentrated on the role of Levosimendan in surgical procedure such as transcathter aortic intervention. This double-blind, randomized, placebo-controlled study is aimed to investigate the effectiveness and safety of Levosimendan in adults having severe aortic stenosis combined with heart failure undergoing transcatheter aortic valve replacement. Therefore, the purpose of this trial is to explore whether the improvement of cardiac and renal performance can be rendered by intra-operative Levosimendan infusion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 124
• Est. completion date: December 30, 2022
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Signed (by the subjects or their legally acceptable representatives) informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

2. Severe aortic stenosis

1. Mean transaortic gradient = 40 mmHg(at rest or stress)

2. Aortic peak velocity = 4m/s;

3. Arotic valve area <0.8 cm2 and/or aortic valve area index< 0.5cm2/m2

3. Cardiac dysfunction

1. LVEF=50% (estimated by Simpson)

2. NT-proBNP=1500ng/L;

3. Symptoms of dyspnea and fatigue when at rest or after slight exertion (New York Heart Association = ? -?)

4. Intermittant fluid retention and/or symptoms induced by low cardiac output at rest, but lack of hemodynamic instability

Exclusion Criteria:

1. Decompensated acute cardiac failure due to hemodynamic instability

2. A historty of torsade de points ventricular tachycardia

3. Known allergic reaction or sensitivity to Levosimendan or excipients

4. Received levosimendan within 1 week prior to the planned clinical trial

5. Serum potassium < 3.5 mmol/L and > 5.5 mmol/L before the drug study

6. Systolic blood pressure < 90mmHg at baseline

7. Estimated glomerular filtration rate (eGFR) =30 mL/min/1.73m2.

8. Unable to participate in study for being critically ill asssed by clinicians

9. Other concomitant severe morbidities leading to poor prognosis and decreased mortality, such as malignant tumor and disease involving other vital organs; life expectancy less than 1 year.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Cardiac Event
• Constriction, Pathologic
• Effect of Drug
• Heart Failure
• Inotropic Agents
• Safety Issues
• Transcatheter Aortic Valve Replacement

Intervention

Drug:
• Levosimendan
On the basis of routine care given by corresponding clinicians, 0.1µg/kg/min levosimendan is given for 24 hours.

Other:
• Placebo
On the basis of routine care given by corresponding clinicians, 0.1µg/kg/min 5% glucose infusion is given for 24 hours.

Locations

Country	Name	City	State
China	Jianhui Wang	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
China National Center for Cardiovascular Diseases	China International Medical Foundation

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The incidence of adverse events	Adverse events include hypotension and arrythmia.	Peri-operation
Other	The incidence of atrial fibrillation		Peri-operation
Other	The change of electrolyte	The change of electrolyte is evaluated by potassium, calcium and lactic acid level.	Peri-operation
Other	The number of patients having liver dysfunction	Liver dysfunction is assessed by the change of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).	Peri-operation
Other	The length of intensive care unit stay		From date of surgery until intensive care unit discharge (assessed up to 1 month)
Other	In-hospital medical expense		From baseline until hospital discharge (assessed up to 1 month)
Primary	The change of NT-proBNP level		day 1, day 3, day 5, month 1 and month 3
Secondary	The change of CK-MB		day 1, day 3, day 5, month 1 and month 3
Secondary	The change of c-TnI		day 1, day 3, day 5, month 1 and month 3
Secondary	The change of left ventricular ejection fraction	It is evaluated by echcardiography.	day 1, day 3, day 5, month 1 and month 3
Secondary	The change of left ventricular end-diastolic diameter	It is evaluated by echcardiography.	day 1, day 3, day 5, month 1 and month 3
Secondary	The number of patients in need of secondary intra-operative vasoactive-inotropic substances	Vasoactive-inotropic substances include dobutamine, milrinone, epinephrine, dopamine and vasopressors.	Peri-operation
Secondary	The incidence of postoperative kidney injury	The kidney injury will be assessed by the change of serum creatinine, urea nitrogen and cystatin C.	day 1, day 3, day 5, month 1 and month 3