Clinical trial NCT04573049: The Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Aortic Valve Stenosis
Heart Failure
Inotropic Agents
Safety Issues
Effect of Drug
Cardiac Event
Transcatheter Aortic Valve Replacement
Keywords: Aortic valve stenosis
Heart failure
Levosimendan
Transcatheter Aortic Valve Replacement
Effectiveness
Safety
NT-proBNP
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
Collaborators: name: China International Medical Foundation
First posted: 2020-10-05
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The change of NT-proBNP level
timeFrame: day 1, day 3, day 5, month 1 and month 3
Secondary outcomes:
measure: The change of CK-MB
timeFrame: day 1, day 3, day 5, month 1 and month 3
measure: The change of c-TnI
timeFrame: day 1, day 3, day 5, month 1 and month 3
measure: The change of left ventricular ejection fraction
timeFrame: day 1, day 3, day 5, month 1 and month 3
measure: The change of left ventricular end-diastolic diameter
timeFrame: day 1, day 3, day 5, month 1 and month 3
measure: The number of patients in need of secondary intra-operative vasoactive-inotropic substances
timeFrame: Peri-operation
measure: The incidence of postoperative kidney injury
timeFrame: day 1, day 3, day 5, month 1 and month 3
Other outcomes:
measure: The incidence of adverse events
timeFrame: Peri-operation
measure: The incidence of atrial fibrillation
timeFrame: Peri-operation
measure: The change of electrolyte
timeFrame: Peri-operation
measure: The number of patients having liver dysfunction
timeFrame: Peri-operation
measure: The length of intensive care unit stay
timeFrame: From date of surgery until intensive care unit discharge (assessed up to 1 month)
measure: In-hospital medical expense
timeFrame: From baseline until hospital discharge (assessed up to 1 month)
Locations:
city: Beijing
country: China
facility: Jianhui Wang
state: Beijing
Study officials:
References: