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

Phase 4

• Conditions: Heart Failure; Effect of Drug; Cardiac Event; Inotropic Agents; Safety Issues; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis
• Interventions: Other: Placebo; Drug: Levosimendan

• Registration Number: NCT04573049
• Lead Sponsor: China National Center for Cardiovascular Diseases

Brief 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

Detailed 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.

Study Timeline

• Status Verified: 2020-09
• Study Start: 2020-09-01
• Study First Submitted: 2020-09-15
• Study First Submitted QC: 2020-09-27
• Last Update Submitted: 2020-09-27
• Study First Posted: 2020-10-05
• Last Update Posted: 2020-10-05
• Primary Completion: 2022-04-01
• Study Completion: 2022-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 124

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	5% glucose 0.1µg/kg/min administration will continue for 24h after the valve is released.
Levosimendan	Levosimendan	Levosimendan 0.1µg/kg/min will last for 24h after the valve is released.

Primary Outcome Measures

Name	Time	Method
The change of NT-proBNP level	day 1, day 3, day 5, month 1 and month 3

Secondary Outcome Measures

Name	Time	Method
The change of CK-MB	day 1, day 3, day 5, month 1 and month 3
The change of c-TnI	day 1, day 3, day 5, month 1 and month 3
The change of left ventricular ejection fraction	day 1, day 3, day 5, month 1 and month 3	It is evaluated by echcardiography.
The change of left ventricular end-diastolic diameter	day 1, day 3, day 5, month 1 and month 3	It is evaluated by echcardiography.
The number of patients in need of secondary intra-operative vasoactive-inotropic substances	Peri-operation	Vasoactive-inotropic substances include dobutamine, milrinone, epinephrine, dopamine and vasopressors.
The incidence of postoperative kidney injury	day 1, day 3, day 5, month 1 and month 3	The kidney injury will be assessed by the change of serum creatinine, urea nitrogen and cystatin C.

Trial Locations

Locations (1)

Jianhui Wang; 🇨🇳 Beijing, Beijing, China