Volume Challenge Added to DSE in the Diagnosis of Severe LFLGAS (FLOW-AS)
Primary Purpose
Aortic Valve Stenosis
Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Volume Challenge
Sponsored by
About this trial
This is an interventional diagnostic trial for Aortic Valve Stenosis focused on measuring Low - flow, Low - gradient, Low - dose dobutamine, Volume challenge, Echocardiography
Eligibility Criteria
Inclusion Criteria:
- Age > 18 years
- Written informed consent
- Patients with LFLGAS (mean Gradient: < 40 mmHg, AVA ≤ 1.0 cm2 (by continuity equation using LVOT diameter) SVI ≤ 35 ml/m2), by rest TTE
Exclusion Criteria:
- Hypersensitivity to dobutamine or midazolam
- Lack of safe contraception defined as: Female participants of childbearing potential not using and not willing to continue contraception for study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices.
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.,
- Enrolment of the investigator, his/her family members, employees and other dependent persons
- Previous enrolment into the current study,
ADDITIONAL SPECIFIC EXCLUSION CRITERIA REGARDING STRESS ECHOCARDIOGRAPHY:
- Systolic left ventricular ejection fraction (LVEF) < 20%
- More than mild aortic regurgitation
- Mitral valve disease, defined by mitral valve area < 2.0 cm2 or more than mild mitral regurgitation
- Unstable angina
- Acute pulmonary oedema
- Signs of relevant left ventricular heart failure defined as crackles more than one fourth of lung field on auscultation
- Signs of relevant right ventricular heart failure defined as central venous pressure (CVP) > 15 mmHg estimated with dilatation and collapsibility of vena cava inferior (VCI)
- Severe pulmonary, renal or hepatic disease
ADDITIONAL SPECIFIC EXCLUSION CRITERIA REGARDING TRANSESOPHAGEAL ECHOCARDIOGRAPHY:
- Oesophageal varices
- History of bariatric surgery
Sites / Locations
- Bern University hospital
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Arm Volume Challenge
Arm Description
A standard LDDSE will be performed. The stroke volume (SV) will be recorded. The addition of VC with the passive leg raise method at peak dobutamine dose will be performed. A TEE with low dose dobutamine and a bolus of normal saline will be performed as a validation method.
Outcomes
Primary Outcome Measures
Diagnosis of true severe AS
Proportion of patients receiving the diagnosis of true severe AS defined as a combination of AVA <1.0 cm2 and ∆SV ≥ 20% will be compared between standard LDDSE and LDDSE with addition of VC
Secondary Outcome Measures
Full Information
NCT ID
NCT03617406
First Posted
July 31, 2018
Last Updated
May 16, 2022
Sponsor
Insel Gruppe AG, University Hospital Bern
1. Study Identification
Unique Protocol Identification Number
NCT03617406
Brief Title
Volume Challenge Added to DSE in the Diagnosis of Severe LFLGAS
Acronym
FLOW-AS
Official Title
Volume Challenge Added to Dobutamine Stress Echocardiography in the Diagnosis of Severe Low-Flow, Low-Gradient Aortic Stenosis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
May 31, 2018 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this study is to test the diagnostic added value of Volume Challenge (VC) to low-dose dobutamine stress echocardiography (LDDSE) in patients with a low-flow, low-gradient aortic stenosis (LFLGAS). This study will assess if LDDSE plus VC allows to increase the proportion of patients in whom a true severe AS can be differentiated from a pseudo severe AS.
Detailed Description
The design of the study is a monocentric prospective non-randomized pilot clinical trial. A standard LDDSE will be performed. The stroke volume (SV) will be recorded. The addition of VC with the passive leg raise method at peak dobutamine dose will be performed. A transesophageal echocardiography (TEE) with low dose dobutamine and a bolus of normal saline will be performed as a validation method to measure AVA with the planimetry method. The SV will be recorded. Proportion of patient receiving the diagnosis of true severe AS defined as a combination of AVA <1.0 cm2 and ∆SV ≥ 20% will be compared between standard LDDSE and LDDSE with addition of VC. Calculating sensitivity, specificity, performing ROC curve analysis and calculating the Youden-index, the accuracy of the test method (LDDSE plus passive leg raising) for the detection of truly severe AS in comparison with the reference method (TEE) will be determined.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Valve Stenosis
Keywords
Low - flow, Low - gradient, Low - dose dobutamine, Volume challenge, Echocardiography
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm Volume Challenge
Arm Type
Other
Arm Description
A standard LDDSE will be performed. The stroke volume (SV) will be recorded. The addition of VC with the passive leg raise method at peak dobutamine dose will be performed. A TEE with low dose dobutamine and a bolus of normal saline will be performed as a validation method.
Intervention Type
Diagnostic Test
Intervention Name(s)
Volume Challenge
Intervention Description
Addition volume challenge with passive leg raising method in LDDSE as well as administration of normal saline and dobutamine during TEE
Primary Outcome Measure Information:
Title
Diagnosis of true severe AS
Description
Proportion of patients receiving the diagnosis of true severe AS defined as a combination of AVA <1.0 cm2 and ∆SV ≥ 20% will be compared between standard LDDSE and LDDSE with addition of VC
Time Frame
Measures taken during echocardiograph a few minutes after administration of VC
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age > 18 years
Written informed consent
Patients with LFLGAS (mean Gradient: < 40 mmHg, AVA ≤ 1.0 cm2 (by continuity equation using LVOT diameter) SVI ≤ 35 ml/m2), by rest TTE
Exclusion Criteria:
Hypersensitivity to dobutamine or midazolam
Lack of safe contraception defined as: Female participants of childbearing potential not using and not willing to continue contraception for study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices.
Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.,
Enrolment of the investigator, his/her family members, employees and other dependent persons
Previous enrolment into the current study,
ADDITIONAL SPECIFIC EXCLUSION CRITERIA REGARDING STRESS ECHOCARDIOGRAPHY:
Systolic left ventricular ejection fraction (LVEF) < 20%
More than mild aortic regurgitation
Mitral valve disease, defined by mitral valve area < 2.0 cm2 or more than mild mitral regurgitation
Unstable angina
Acute pulmonary oedema
Signs of relevant left ventricular heart failure defined as crackles more than one fourth of lung field on auscultation
Signs of relevant right ventricular heart failure defined as central venous pressure (CVP) > 15 mmHg estimated with dilatation and collapsibility of vena cava inferior (VCI)
Severe pulmonary, renal or hepatic disease
ADDITIONAL SPECIFIC EXCLUSION CRITERIA REGARDING TRANSESOPHAGEAL ECHOCARDIOGRAPHY:
Oesophageal varices
History of bariatric surgery
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Seiler, MD
Organizational Affiliation
University Clinic for Cardiology, Inselspital, Bern
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stefano de Marchi, MD
Organizational Affiliation
University Clinic for Cardiology, Inselspital, Bern
Official's Role
Study Chair
Facility Information:
Facility Name
Bern University hospital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
12. IPD Sharing Statement
Learn more about this trial
Volume Challenge Added to DSE in the Diagnosis of Severe LFLGAS
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