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

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ClinicalTrials.gov Identifier: NCT03505788
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
Wilfried Mullens, Ziekenhuis Oost-Limburg

Brief 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.

Condition or disease Intervention/treatment Phase
Acute Decompensated Heart Failure Volume Overload Drug: Acetazolamide Drug: Placebo Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 519 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 11, 2018
Estimated Primary Completion Date : October 5, 2020
Estimated Study Completion Date : January 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Mortality [ Time Frame: 3 months ]
    All-cause mortality during the first 3 months after start of the study

  2. Hospital readmission [ Time Frame: 3 months ]
    If a patient is readmitted to the hospital within 3 months, this data will be collected

  3. Length of index hospital admission [ Time Frame: 3 months ]
    The time frame between hospital admission and discharge will be calculated

  4. 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.


Other Outcome Measures:
  1. Body weight [ Time Frame: day 1, day 2, day3, day 4 ]
    Body weight change after day 1, 2, 3, 4 discharge compared to admission

  2. Use of medication [ Time Frame: 3 months ]
    A list of specific medication will be collected

  3. 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.

  4. Adverse events [ Time Frame: 3 months ]
    Any undesired clinical outcomes will be reported

  5. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03505788


Contacts
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Contact: Wilfried Mullens, MD PhD +3289327325 wilfried.mullens@zol.be
Contact: Katrien Tartaglia +3289327325 katrien.tartaglia@zol.be

Locations
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Belgium
Ziekenhuis Oost-Limburg AV Recruiting
Genk, Limburg, Belgium, 3600
Contact: Wilfried Mullens, MD PhD    +32 89 32 7325      
Sponsors and Collaborators
Ziekenhuis Oost-Limburg
Investigators
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Principal Investigator: Wiflried Mullens, MD PhD Ziekenhuis Oost-Limburg

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Responsible Party: Wilfried Mullens, Principal Investigator, Ziekenhuis Oost-Limburg
ClinicalTrials.gov Identifier: NCT03505788     History of Changes
Other Study ID Numbers: ZOLCAR17001
First Posted: April 23, 2018    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Diuretics
Acetazolamide
Sodium Potassium Chloride Symporter Inhibitors
Natriuretic Agents
Physiological Effects of Drugs
Anticonvulsants
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Membrane Transport Modulators