Efficacy and Safety of Combination Diuretic Therapy in Patients With Acute Decompensated Heart Failure and Volume Overload

Phase 4

Recruiting

• Conditions: Acute Decompensated Heart Failure; Volume Overload; Edema
• Interventions: Drug: Acetazolamide; Drug: Metolazone; Drug: IV Loop Diuretics

• Registration Number: NCT06414759
• Lead Sponsor: Cairo University

Brief Summary

This study aims to compare two medications, acetazolamide and metolazone, along with loop diuretics, to see which one works better and is safer for patients with ADHF who have volume overload. By comparing these medications, we hope to learn which one can help these patients the most. This will help doctors choose the best treatment for patients with ADHF and volume overload.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-08
• Study First Submitted QC: 2024-05-13
• Study First Posted: 2024-05-16
• Status Verified: 2024-07
• Study Start: 2024-07-01
• Last Update Submitted: 2024-07-23
• Last Update Posted: 2024-07-24
• Primary Completion: 2024-12-30
• Study Completion: 2025-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

• Male or female patients with ages ≥ 18 years old, and less than 65 years old.
• For both elective and emergency hospital admissions, patients with a clinical diagnosis of ADHF must exhibit at least one clinical sign indicative of volume overload. These signs may include edema (score 2 or higher), ascites confirmed through echography, or pleural effusion confirmed by chest X-ray or echography or rales on auscultation, or jugular venous pressure greater than10 mm Hg.

Exclusion Criteria

• Patient diagnosed with acute kidney injury upon hospital admission based on the presence of any of the following criteria: an increase in SCr by at least 0.3 mg/dL within 48 hours, an increase in SCr to at least 2 times the baseline value, known or presumed to have occurred within the prior 7 days, and a urine volume less than 0.5 ml/kg/hour for a duration of 6 hours.
• Patients with acute pulmonary edema caused by increased afterload and fluid redistribution to the lungs in the absence or with minimal fluid accumulation.
• Anticipated exposure to nephrotoxic agents (such as contrast dye) during hospitalization.
• Patients who exhibit anuria or are undergoing renal replacement therapy or ultrafiltration.
• Patients with eGFR less than 30 mL/min/1.73m² at the time of screening.
• Expected use of intravenous inotropes, vasopressors, or nitroprusside during the study.
• Prior cardiac transplantation and/or utilization of a ventricular assist device.
• Blood pressure below 90 mmHg or mean arterial pressure below 65 mmHg at the time of recruitment.
• Patients who are pregnant or breastfeeding.
• Administration of acetazolamide or metolazone within the one-month period preceding randomization.
• The usage of any diuretic agent during the treatment phase is not specified in the study protocol, except for mineralocorticoid receptor antagonists.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	IV Loop Diuretics	First group (IV loop Diuretics + oral acetazolamide): patients will receive IV loop diuretic 2 times the outpatient oral (PO) daily dose, and oral loop diuretics will be stopped. In cases where the patient was not previously on oral diuretics, a starting dose of 40 mg of IV furosemide, IV bumetanide 1 mg or a bolus of 20 mg of IV torsemide can be utilized, together with acetazolamide: 500 mg PO once daily.
Group 2	IV Loop Diuretics	Second group (IV loop diuretics + oral metolazone): patients will receive IV loop diuretic approximately 2 times the outpatient oral daily dose, and oral loop diuretics will be stopped. In cases where the patient was not previously on oral diuretics, a starting dose of 40 mg of IV furosemide, IV bumetanide 1 mg or a bolus of 20 mg of IV torsemide can be utilized, together with metolazone: 5 mg PO once daily.
Group 1	Acetazolamide	First group (IV loop Diuretics + oral acetazolamide): patients will receive IV loop diuretic 2 times the outpatient oral (PO) daily dose, and oral loop diuretics will be stopped. In cases where the patient was not previously on oral diuretics, a starting dose of 40 mg of IV furosemide, IV bumetanide 1 mg or a bolus of 20 mg of IV torsemide can be utilized, together with acetazolamide: 500 mg PO once daily.
Group 2	Metolazone	Second group (IV loop diuretics + oral metolazone): patients will receive IV loop diuretic approximately 2 times the outpatient oral daily dose, and oral loop diuretics will be stopped. In cases where the patient was not previously on oral diuretics, a starting dose of 40 mg of IV furosemide, IV bumetanide 1 mg or a bolus of 20 mg of IV torsemide can be utilized, together with metolazone: 5 mg PO once daily.

Primary Outcome Measures

Name	Time	Method
Urine Output	48 Hours	Total Urine output Volume

Secondary Outcome Measures

Name	Time	Method
Body Weight	48 Hours	Change in Body Weight
Diuretic Response	48 Hours	Urine output/40 mg furosemide equivalent
Congestion Score	48 Hours	Change in congestion score (Modified ADVOR Trial Congestion Score)
Bicarbonate Level	48 Hours	Change in bicarbonate level from baseline \[VBG\]
Serum Creatinine	48 Hours	Change in serum creatinine (SCr)
eGFR	48 Hours	Change in estimated glomerular filtration rate (eGFR) from baseline
NT-proBNP/BNP	On admission and before discharge (After 48 hours)	Change in NT-Pro BNP/BNP levels
Blood Pressure	48 Hours	Change in systolic blood pressure (SBP) from baseline
Potassium Level	48 Hours	Change in potassium level from baseline \[VBG\]
Length of Hospital Stay	Up to 2 weeks	Both general ward and CCU
Mortality or HF Events	3 Months	All-cause mortality and heart failure readmission during 3 months of follow-up

Trial Locations

Locations (1)

National Heart Institute; 🇪🇬 Giza, GZ, Egypt