- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03505788
Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR) (Advor)
A Multi-center, Randomized, Double-blind, Phase IV Clinical Trial on the Diuretic Effects of Acetazolamide in Patients With Decompensated Heart Failure and Volume OveRload
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a randomized, double blind study with 2 treatment groups. This means that the patients will be randomized to one of the two treatment groups by chance. Patients randomized to the first group will receive standard treatment with high doses of intravenous loop diuretics and a placebo. Patients randomized to the other treatment group will receive a combination of the same doses of loop diuretics and an additional diuretic, acetazolamide (Diamox®). All diuretics will be administered intravenously. It is expected that the patients of the treatment group with the combination therapy will have a faster reduction of their fluid overload. In consequence the treatment duration and total dose of diuretics administered will be shorter. Acetazolamide (Diamox®) is a diuretic that acts at a different location in the kidney compared to the loop diuretics. This mutual reinforcement will probably reduce the total dose and duration of the diuretics.
The study will start during the hospitalization and will last around 3 months.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Limburg
-
Genk, Limburg, Belgium, 3600
- Ziekenhuis Oost-Limburg AV
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Signed written informed consent must be obtained before any study assessment is performed
- Male or female patients 18 years of age or older
- An elective or emergency hospital admission with clinical diagnosis of decompensated HF with at least one clinical sign of volume overload (e.g. oedema (score 2 or more), ascites confirmed by echography or pleural effusion confirmed by chest X-ray or echography)
- Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide or an equivalent dose for at least 1 month before hospital admission (Conversion: 1 mg bumetanide = 40 mg furosemide = 20 mg torsemide)
- Plasma NT-proBNP levels >1000 ng/mL or BNP levels >250 ng/mL at the time of screening.
- Assessed LVEF by any imaging technique; i.e. echocardiography, catheterization, nuclear scan or magnetic resonance imaging within 12 months of inclusion
Exclusion Criteria:
- Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain in addition to a troponin rise above the 99th percentile and/or electrocardiographic changes suggestive of cardiac ischemia
- History of congenital heart disease requiring surgical correction
- History of a cardiac transplantation and/or ventricular assist device
- Systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg at the moment of admission
- Expected use of intravenous inotropes, vasopressors or nitroprusside during the study. Use of nitrates is allowed only if the patient's systolic blood pressure is >140 mmHg
- Estimated glomerular filtration rate <20 mL/min/1.73m² at screening
- Use of renal replacement therapy or ultrafiltration at any time before study inclusion
- Treatment with acetazolamide during the index hospitalization and prior to randomization
- Exposure to nephrotoxic agents (i.e. contrast dye) anticipated within the next 3 days
- Use of any non-protocol defined diuretic agent with the exception of mineralocorticoid receptor antagonists. Thiazides, metolazone, indapamide and amiloride should be stopped upon study inclusion. If patient is taking a combination drug including a thiazide-type diuretic, the thiazide-type diuretic should be stopped
- Current use of sodium-glucose transporter-2 inhibitors
- Subjects who are pregnant or breastfeeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: high-dose loop diuretics+placebo
|
In the placebo group, the patient will receive the standard of care loop diuretics and the placebo
|
Experimental: high-dose loop diuretics+acetazolamide
|
In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment success
Time Frame: 4 days
|
Treatment success (decongestion achieved) on the morning of day 4 without the need for escalating diuretic strategy on the morning of day 3.
|
4 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality
Time Frame: 3 months
|
All-cause mortality during the first 3 months after start of the study
|
3 months
|
Hospital readmission
Time Frame: 3 months
|
If a patient is readmitted to the hospital within 3 months, this data will be collected
|
3 months
|
Length of index hospital admission
Time Frame: 3 months
|
The time frame between hospital admission and discharge will be calculated
|
3 months
|
EuroQoL five dimensions questionnaire (EQ-5D)
Time Frame: at day 1, day 4, at any hospital readmission within 3 months, at 3 months
|
A questionnaire about the patients' quality of life will be performed at baseline, the morning of day 4, at any readmission, 3 months.
The questionnaire is divided into 5 levels of severity with a score varying from 1 to 5. 1 indicates no problems and 5 indicates severe problems.
|
at day 1, day 4, at any hospital readmission within 3 months, at 3 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Body weight
Time Frame: day 1, day 2, day3, day 4
|
Body weight change after day 1, 2, 3, 4 discharge compared to admission
|
day 1, day 2, day3, day 4
|
Use of medication
Time Frame: 3 months
|
A list of specific medication will be collected
|
3 months
|
Diureses and natriuresis
Time Frame: 3 days
|
The volume of urine will be measured until the morning of day 3.
In the same urine, natriuresis will be assessed.
|
3 days
|
Adverse events
Time Frame: 3 months
|
Any undesired clinical outcomes will be reported
|
3 months
|
Abnormal blood parameters
Time Frame: an average of 7 days
|
Any abnormal laboratory parameters in the blood (electrolytes, heart failure markers and anemia markers) during hospital admission will be reported
|
an average of 7 days
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wiflried Mullens, MD PhD, Ziekenhuis Oost-Limburg
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ZOLCAR17001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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