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

National Center for Cardiovascular Diseases

Status and phase: Unknown; Phase 4

Conditions: Transcatheter Aortic Valve Replacement; Inotropic Agents; Aortic Valve Stenosis; Safety Issues; Heart Failure; Effect of Drug; Cardiac Event

Treatments: Other: Placebo; Drug: Levosimendan

Study type: Interventional

Funder types: Other

Identifiers

NCT04573049

2020-1357

Details and patient eligibility

About

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

Full 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.

Enrollment: 124 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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 ≥ Ⅲ -Ⅳ)
   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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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124 participants in 2 patient groups, including a placebo group

Levosimendan

Experimental group

Description:

Levosimendan 0.1µg/kg/min will last for 24h after the valve is released.

Treatment:

Drug: Levosimendan

Placebo

Placebo Comparator group

Description:

5% glucose 0.1µg/kg/min administration will continue for 24h after the valve is released.

Treatment:

Other: Placebo