Back to resultsThe Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement
Primary Purpose
Aortic Valve Stenosis, Heart Failure, Inotropic Agents
Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Levosimendan
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Aortic Valve Stenosis focused on measuring Aortic valve stenosis, Heart failure, Levosimendan, Transcatheter Aortic Valve Replacement, Effectiveness, Safety, NT-proBNP
Eligibility Criteria
Inclusion Criteria:
- 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
Severe aortic stenosis
- Mean transaortic gradient ≥ 40 mmHg(at rest or stress)
- Aortic peak velocity ≥ 4m/s;
- Arotic valve area <0.8 cm2 and/or aortic valve area index< 0.5cm2/m2
Cardiac dysfunction
- LVEF≤50% (estimated by Simpson)
- NT-proBNP≥1500ng/L；
- Symptoms of dyspnea and fatigue when at rest or after slight exertion (New York Heart Association ≥ Ⅲ -Ⅳ)
- Intermittant fluid retention and/or symptoms induced by low cardiac output at rest, but lack of hemodynamic instability
Exclusion Criteria:
- Decompensated acute cardiac failure due to hemodynamic instability
- A historty of torsade de points ventricular tachycardia
- Known allergic reaction or sensitivity to Levosimendan or excipients
- Received levosimendan within 1 week prior to the planned clinical trial
- Serum potassium < 3.5 mmol/L and > 5.5 mmol/L before the drug study
- Systolic blood pressure < 90mmHg at baseline
- Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m2.
- Unable to participate in study for being critically ill asssed by clinicians
- 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.
Sites / Locations
- Jianhui WangRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Levosimendan
Placebo
Arm Description
Levosimendan 0.1µg/kg/min will last for 24h after the valve is released.
5% glucose 0.1µg/kg/min administration will continue for 24h after the valve is released.
Outcomes
Primary Outcome Measures
The change of NT-proBNP level
Secondary Outcome Measures
The change of CK-MB
The change of c-TnI
The change of left ventricular ejection fraction
It is evaluated by echcardiography.
The change of left ventricular end-diastolic diameter
It is evaluated by echcardiography.
The number of patients in need of secondary intra-operative vasoactive-inotropic substances
Vasoactive-inotropic substances include dobutamine, milrinone, epinephrine, dopamine and vasopressors.
The incidence of postoperative kidney injury
The kidney injury will be assessed by the change of serum creatinine, urea nitrogen and cystatin C.
Full Information
NCT ID
NCT04573049
First Posted
September 15, 2020
Last Updated
September 27, 2020
Sponsor
China National Center for Cardiovascular Diseases
Collaborators
China International Medical Foundation
1. Study Identification
Unique Protocol Identification Number
NCT04573049
Brief Title
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
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
April 1, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
China National Center for Cardiovascular Diseases
Collaborators
China International Medical Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
124 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Levosimendan
Arm Type
Experimental
Arm Description
Levosimendan 0.1µg/kg/min will last for 24h after the valve is released.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
5% glucose 0.1µg/kg/min administration will continue for 24h after the valve is released.
Intervention Type
Drug
Intervention Name(s)
Levosimendan
Intervention Description
On the basis of routine care given by corresponding clinicians, 0.1µg/kg/min levosimendan is given for 24 hours.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
On the basis of routine care given by corresponding clinicians, 0.1µg/kg/min 5% glucose infusion is given for 24 hours.
Primary Outcome Measure Information:
Title
The change of NT-proBNP level
Time Frame
day 1, day 3, day 5, month 1 and month 3
Secondary Outcome Measure Information:
Title
The change of CK-MB
Time Frame
day 1, day 3, day 5, month 1 and month 3
Title
The change of c-TnI
Time Frame
day 1, day 3, day 5, month 1 and month 3
Title
The change of left ventricular ejection fraction
Description
It is evaluated by echcardiography.
Time Frame
day 1, day 3, day 5, month 1 and month 3
Title
The change of left ventricular end-diastolic diameter
Description
It is evaluated by echcardiography.
Time Frame
day 1, day 3, day 5, month 1 and month 3
Title
The number of patients in need of secondary intra-operative vasoactive-inotropic substances
Description
Vasoactive-inotropic substances include dobutamine, milrinone, epinephrine, dopamine and vasopressors.
Time Frame
Peri-operation
Title
The incidence of postoperative kidney injury
Description
The kidney injury will be assessed by the change of serum creatinine, urea nitrogen and cystatin C.
Time Frame
day 1, day 3, day 5, month 1 and month 3
Other Pre-specified Outcome Measures:
Title
The incidence of adverse events
Description
Adverse events include hypotension and arrythmia.
Time Frame
Peri-operation
Title
The incidence of atrial fibrillation
Time Frame
Peri-operation
Title
The change of electrolyte
Description
The change of electrolyte is evaluated by potassium, calcium and lactic acid level.
Time Frame
Peri-operation
Title
The number of patients having liver dysfunction
Description
Liver dysfunction is assessed by the change of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Time Frame
Peri-operation
Title
The length of intensive care unit stay
Time Frame
From date of surgery until intensive care unit discharge (assessed up to 1 month)
Title
In-hospital medical expense
Time Frame
From baseline until hospital discharge (assessed up to 1 month)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Severe aortic stenosis
Mean transaortic gradient ≥ 40 mmHg(at rest or stress)
Aortic peak velocity ≥ 4m/s;
Arotic valve area <0.8 cm2 and/or aortic valve area index< 0.5cm2/m2
Cardiac dysfunction
LVEF≤50% (estimated by Simpson)
NT-proBNP≥1500ng/L；
Symptoms of dyspnea and fatigue when at rest or after slight exertion (New York Heart Association ≥ Ⅲ -Ⅳ)
Intermittant fluid retention and/or symptoms induced by low cardiac output at rest, but lack of hemodynamic instability
Exclusion Criteria:
Decompensated acute cardiac failure due to hemodynamic instability
A historty of torsade de points ventricular tachycardia
Known allergic reaction or sensitivity to Levosimendan or excipients
Received levosimendan within 1 week prior to the planned clinical trial
Serum potassium < 3.5 mmol/L and > 5.5 mmol/L before the drug study
Systolic blood pressure < 90mmHg at baseline
Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m2.
Unable to participate in study for being critically ill asssed by clinicians
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianhui Wang, MD
Phone
010-88398082
Email
stewenwang@sina.com
Facility Information:
Facility Name
Jianhui Wang
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100037
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianhui Wang, MD
Phone
010-88398082
Email
stewenwang@sina.com
12. IPD Sharing Statement
Learn more about this trial
The Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement
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