Clinical trial NCT06475105: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Decompensated Heart Failure
Keywords: Oral Acetazolamide
Acute Decompensated Heart Failure
Congestion
Lead sponsor: Universitas Diponegoro
Sponsor class: OTHER
First posted: 2024-06-26
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This research is an experimental clinical study with a double blinded randomized controlled trial design. The study group consisted of patients with acute decompensated heart failure with volume overload who required intravenous diuretic therapy. The first group was patients who received intravenous furosemide plus acetazolamide 250 mg / 12 hours orally for up to 3 days (group A). Meanwhile, the second group was patients who received intravenous furosemide plus placebo for up to 3 days (group B).
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Successful Decongestion
timeFrame: within 3 days
Secondary outcomes:
measure: NT pro BNP
timeFrame: within 3 days
measure: Renal Function
timeFrame: 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
measure: Urinary Output
timeFrame: From date of randomization until participants discharge from hospital up to 7 days post discharge.
measure: Length of Stay
timeFrame: 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.
Other outcomes:
Locations:
city: Semarang
country: Indonesia
facility: Department of Cardiology and Vascular Medicine, Universitas Diponegoro, Kariadi Central General Hospital
state: Central Java
city: Semarang
country: Indonesia
facility: Kariadi Central General Hospital
state: Central Java
Study officials:
affiliation: Department Cardiology and Vascular Medicine Universitas Diponegoro Kariadi General Hospital
name: Ilham Uddin, MD
role: PRINCIPAL_INVESTIGATOR
References: