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

May 13, 2024 updated by: Mohamed Ahmed Naguib Mohamed Abdelmoaty, Cairo University
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

110

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
    • GZ
      • Giza, GZ, Egypt, 3755204
        • National Heart Institute
        • Contact:
        • Contact:
          • Bassem Zarif, PhD, Cardiology
          • Phone Number: +201223950548
        • Principal Investigator:
          • Mohamed AN Abdelmoaty, B.Sc. Pharmaceutical Sciences
        • Principal Investigator:
          • Nirmeen Sabry, PhD, Clinical Pharmacy
        • Principal Investigator:
          • Bassem Zarif, PhD, Cardiology
        • Principal Investigator:
          • Sahar Atef, PhD, Clinical Pharmacy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
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.
Drug: Acetazolamide

Acetazolamide is a medication that belongs to the class of carbonic anhydrase inhibitors. It acts by reducing the reabsorption of sodium in the proximal tubules of the kidneys. When combined with loop diuretics, acetazolamide has the potential to enhance the effectiveness of diuretic therapy, thus aiding in the process of decongestion.

It will be given 500mg orally, once daily.

Other Names:
  • Carbonic anhydrase inhibitor
Drug: IV Loop Diuretics
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.
Experimental: Group 2
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.
Drug: IV Loop Diuretics
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.
Drug: Metolazone

Metolazone is a medication with properties like thiazide diuretics, prescribed for the management of congestive heart failure and hypertension. Its mechanism of action involves blocking the transport of sodium across the epithelium of renal tubules, predominantly in the distal tubules.

It will be given 5mg orally, once daily.

Other Names:
  • Thiazide like diuretic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urine Output
Time Frame: 48 Hours
Total Urine output Volume
48 Hours

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cairo University

Collaborators

National Heart Institute, Egypt

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 22, 2024

Primary Completion (Estimated)

December 30, 2024

Study Completion (Estimated)

March 30, 2025

Study Registration Dates

First Submitted

May 8, 2024

First Submitted That Met QC Criteria

May 13, 2024

First Posted (Actual)

May 16, 2024

Study Record Updates

Last Update Posted (Actual)

May 16, 2024

Last Update Submitted That Met QC Criteria

May 13, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CL3575
  • IHC00077 (Registry Identifier: General Organization for Teaching Hospitals and Institutes (GOTHI))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Edema

Clinical Trials on Acetazolamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mexico

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe