Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR)

NCT03505788 | Completed Phase 4 Results

• 1 other identifier: ZOLCAR17001
• Study Type: interventional
• Target: 519
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Decompensated Heart Failure; Volume Overload

Outcome Measures

Primary Outcomes (1)

• Successful Decongestion

  defined as the absence of signs of volume overload, within 3 days after randomization and with no indication for escalation of decongestive therapy.

  4 days

Secondary Outcomes (4)

• Mortality

  3 months

• Hospital Readmission

  3 months

• Length of Index Hospital Admission

  3 months

• EuroQoL Five Dimensions Questionnaire (EQ-5D)

  at baseline, day 4 (or discharge), at 3 months

Study Arms (2)

high-dose loop diuretics+placebo

PLACEBO COMPARATOR

* 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

high-dose loop diuretics+acetazolamide

EXPERIMENTAL

* 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

Interventions

Acetazolamide DRUG

In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide

high-dose loop diuretics+acetazolamide

Placebo DRUG

In the placebo group, the patient will receive the standard of care loop diuretics and the placebo

high-dose loop diuretics+placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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
• Current use of sodium-glucose transporter-2 inhibitors
• Subjects who are pregnant or breastfeeding

Sponsors & Collaborators

• Ziekenhuis Oost-Limburg: lead

Study Sites (1)

Ziekenhuis Oost-Limburg AV

Genk, Limburg, 3600, Belgium

Location

Related Publications (5)

• Van den Eynde J, Martens P, Dauw J, Nijst P, Meekers E, Ter Maaten JM, Damman K, Filippatos G, Lassus J, Mebazaa A, Ruschitzka F, Dupont M, Mullens W, Verbrugge FH. Serum Chloride and the Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload: A Post Hoc Analysis From the ADVOR Trial. Circ Heart Fail. 2024 Oct;17(10):e011749. doi: 10.1161/CIRCHEARTFAILURE.123.011749. Epub 2024 Aug 22.

  PMID: 39171394 DERIVED

• Meekers E, Dauw J, Martens P, Dhont S, Verbrugge FH, Nijst P, Ter Maaten JM, Damman K, Mebazaa A, Filippatos G, Ruschitzka F, Tang WHW, Dupont M, Mullens W. Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial. Eur Heart J. 2023 Oct 1;44(37):3672-3682. doi: 10.1093/eurheartj/ehad557.

  PMID: 37623428 DERIVED

• Verbrugge FH, Martens P, Dauw J, Nijst P, Meekers E, Augusto SN Jr, Ter Maaten JM, Damman K, Filippatos G, Lassus J, Mebazaa A, Ruschitzka F, Dupont M, Mullens W. Natriuretic Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload. J Am Coll Cardiol. 2023 May 23;81(20):2013-2024. doi: 10.1016/j.jacc.2023.03.400.

  PMID: 37197845 DERIVED

• Martens P, Dauw J, Verbrugge FH, Nijst P, Meekers E, Augusto SN Jr, Ter Maaten JM, Damman K, Mebazaa A, Filippatos G, Ruschitzka F, Tang WHW, Dupont M, Mullens W. Decongestion With Acetazolamide in Acute Decompensated Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction: A Prespecified Analysis From the ADVOR Trial. Circulation. 2023 Jan 17;147(3):201-211. doi: 10.1161/CIRCULATIONAHA.122.062486. Epub 2022 Nov 6.

  PMID: 36335479 DERIVED

• Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, Tartaglia K, Chenot F, Moubayed S, Dierckx R, Blouard P, Troisfontaines P, Derthoo D, Smolders W, Bruckers L, Droogne W, Ter Maaten JM, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M; ADVOR Study Group. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27.

  PMID: 36027559 DERIVED

MeSH Terms

Conditions

Edema

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

1. Nearly all patients were white 2. Patients had a history of chronic heart failure and had been receiving long-term outpatient treatment with at least 40 mg of furosemide equivalent. 3. Patients in the two trial groups received similar loop diuretics. 4. The congestion score focused on the presence of edema in the lower limb, pleural effusion, and ascites - reflective of mainly extracellular volume overload 5. The trial design excluded use of SGLT2 inhibitors

Results Point of Contact

• Title: Prof. dr. Wilfried Mullens
• Organization: Ziekenhuis Oost-Limburg

wilfried.mullens@zol.be

+32(0)89327140

Study Officials

• Wiflried Mullens, MD PhD

  Ziekenhuis Oost-Limburg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2018
• First Posted: April 23, 2018
• Study Start: November 11, 2018
• Primary Completion: January 20, 2022
• Study Completion: May 16, 2022
• Last Updated: October 28, 2024
• Results First Posted: October 28, 2024

Record last verified: 2024-08

Locations

BE (1)