Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR)

Acute Decompensated Heart Failure Clinical Trial

— Advor  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03505788
• Other study ID #: ZOLCAR17001
• Status: Completed
• Phase: Phase 4
• Start date: November 11, 2018
• Est. completion date: May 16, 2022

Study information

• Verified date: June 2022
• Source: Ziekenhuis Oost-Limburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical research study is being conducted in multiple hospitals in Belgium and approximately 519 patients with acute decompensated heart failure are expected to participate. Large-scale research shows that 90% of the physicians treat volume overload with high doses of loop diuretics. However, there is not a lot of scientific data available regarding the optimal doses of these diuretic medications. In addition, it is observed that a lot of people, treated with these drugs, are being readmitted to the hospital due to a new episode of heart failure. The hypothesis of this study is that the volume overload could be better treated when patients receive a combination of different types of diuretics. Additionally, the total dose of the administrated diuretics might be lower this way.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 519
• Est. completion date: May 16, 2022
• Est. primary completion date: January 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure
• Volume Overload

Intervention

Drug:
• Acetazolamide
In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
• Placebo
In the placebo group, the patient will receive the standard of care loop diuretics and the placebo

Locations

Country	Name	City	State
Belgium	Ziekenhuis Oost-Limburg AV	Genk	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Ziekenhuis Oost-Limburg

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body weight	Body weight change after day 1, 2, 3, 4 discharge compared to admission	day 1, day 2, day3, day 4
Other	Use of medication	A list of specific medication will be collected	3 months
Other	Diureses and natriuresis	The volume of urine will be measured until the morning of day 3. In the same urine, natriuresis will be assessed.	3 days
Other	Adverse events	Any undesired clinical outcomes will be reported	3 months
Other	Abnormal blood parameters	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
Primary	Treatment success	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	Mortality	All-cause mortality during the first 3 months after start of the study	3 months
Secondary	Hospital readmission	If a patient is readmitted to the hospital within 3 months, this data will be collected	3 months
Secondary	Length of index hospital admission	The time frame between hospital admission and discharge will be calculated	3 months
Secondary	EuroQoL five dimensions questionnaire (EQ-5D)	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