Combination Oral Acetazolamide and Intravenous Furosemide on Acute Decompensated Heart Failure Outcomes

Official title

Effects of Combination Oral Acetazolamide and Intravenous Furosemide on Acute Decompensated Heart Failure

Overview

Based on ADVOR trial, the potential of adding acetazolamide in increasing the success of decongestion, the amount of natriuresis and diuresis. However, the use of intravenous acetazolamide may not be possible in Indonesia, where the intravenous formulation is not available. This clinical research study is being conducted in single hospitals in Indonesia. We aim to learn if Oral Acetazolamide in addition to Furosemide intravenous works to treat congestion in Acute Decompensated Heart Failure, besides evaluating the total urinary output, change of NT pro BNP level, and safety profile of oral Acetazolamide. The hypothesis of this study is oral acetazolamide works well to achieve successful decongestion.

Detailed description

This is a randomized, double blind study with 2 treatment groups. Participants diagnosed with ADHF who meet the inclusion criteria and no exclusion criteria are given an explanation regarding the research and additional therapy that will be given, then informed consent is requested. Participants will be randomized to one of the two treatment groups by chance. Patients randomized to the first group will receive intravenous furosemide and oral acetazolamide. Patients randomized to the other treatment group will receive a combination of iv furosemide and placebo. 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.

Interventions

• Drug Oral Acetazolamide
  Participants will be randomized into group receiving either oral acetazolamide or placebo for up to 3 days
• Drug Placebo
  Participants will be randomized into group receiving either oral acetazolamide or placebo for up to 3 days

Primary outcome measures

• Successful Decongestion [Time frame: within 3 days]

Secondary outcome measures (4)

• NT pro BNP [Time frame: within 3 days]
• Renal Function [Time frame: From date of randomization until the date of first documented worsening renal function (increased of creatinine serum level >50% of baseline creatinine) or date of death from any cause, evaluation every 48 hours or whichever came first, up to 90 days]
• Urinary Output [Time frame: From date of randomization until participants discharge from hospital up to 7 days post discharge.]
• Length of Stay [Time frame: From date of randomization until the date of first documented progression and discharge from hospital or date of death from any cause, whichever came first, assessed up to 30 days.]

Eligibility criteria

Inclusion criteria

• Agree to be included in the research by signing informed consent
• Patients with a clinical diagnosis of acute decompensated heart failure with at least one clinical sign of volume overload with a congestion score ≥2 (ADVOR Score) (e.g. edema (score 2 or more), ascites confirmed by physical examination or ultrasonography or pleural effusion confirmed by chest x-ray or echocardiography).
• Patients on routine oral loop diuretic therapy with a dose of ≥40 mg furosemide for ≥1 month
• Plasma NT-proBNP levels that increase ≥300 pg/mL or the applicable cut-off according to the age range at the time of examination in the ER.

Exclusion criteria

• Subjects with acute coronary syndrome
• History of congenital heart disease requiring surgical correction.
• Subjects in cardiogenic shock.
• Estimated glomerular filtration rate <20 mL/min/1.73m² at the time of examination.
• Use of renal replacement therapy or ultrafiltration at any time before the study was included.
• Treatment with acetazolamide within 1 month before randomization.
• Exposure to nephrotoxic agents (i.e. contrast dye) is anticipated within the next 3 days
• Subjects who are pregnant or breastfeeding.
• Subjects with urinary incontinence who are unwilling to use a bladder catheter.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Indonesia · 2 centers

• Department of Cardiology and Vascular Medicine, Universitas Diponegoro, Kariadi Central Ge — Semarang
• Kariadi Central General Hospital — Semarang

Identifiers

NCT: NCT06475105 · No16129/EC/KEPK-RSDK/2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗