Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR) (Advor)

June 2, 2022 updated by: Wilfried Mullens, Ziekenhuis Oost-Limburg

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

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.

Study Overview

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

Interventional

Enrollment (Actual)

519

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Limburg
      • Genk, Limburg, Belgium, 3600
        • Ziekenhuis Oost-Limburg AV

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
  • At the moment of randomization (day 1), oral loop diuretics are stopped and the patient receives IV loop diuretics at a dose equal to the double of his oral daily maintenance dose + 500 mg IV bolus of placebo.
  • If the patient still have signs of volume overload the next mornings (day 2 and day 3), the patient will receive IV loop diuretics at a dose equal to the oral daily maintenance dose + 500 mg IV bolus of placebo. It the patient has no sign of volume overload at these time points, the study treatment will be stopped.
In the placebo group, the patient will receive the standard of care loop diuretics and the placebo
Experimental: high-dose loop diuretics+acetazolamide
  • At the moment of randomization (day 1), oral loop diuretics are stopped and the patient receives IV loop diuretics at a dose equal to the double of his oral daily maintenance dose + 500 mg IV bolus of acetazolamide.
  • If the patient still have signs of volume overload the next mornings (day 2 and day 3), the patient will receive IV loop diuretics at a dose equal to the oral daily maintenance dose + 500 mg IV bolus of acetazolamide. It the patient has no sign of volume overload at these time points, the study treatment will be stopped.
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

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Wiflried Mullens, MD PhD, Ziekenhuis Oost-Limburg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2018

Primary Completion (Actual)

January 20, 2022

Study Completion (Actual)

May 16, 2022

Study Registration Dates

First Submitted

March 28, 2018

First Submitted That Met QC Criteria

April 12, 2018

First Posted (Actual)

April 23, 2018

Study Record Updates

Last Update Posted (Actual)

June 3, 2022

Last Update Submitted That Met QC Criteria

June 2, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

Clinical Trials on Acute Decompensated Heart Failure

Clinical Trials on Placebo

3
Subscribe