The Heart Failure Diuresis Efficacy Comparison (DEA-HF) Study (DEA-HF)

Diuresis Efficacy in Ambulatory Chronic Heart Failure Patients With Volume Overload- Intra -Patient Comparison of Three Diuretics Regimens

To investigate the effectiveness of three (3) IV diuretic regimens to increase natriuresis in volume-overloaded HF patients, allowing for better decongestion and potentially resulting in improved clinical and biochemical parameters outcome.

Study Overview

• Status: Completed
• Conditions: Chronic Heart Failure; Congestive Heart Failure; Diuretics Drug Reactions
• Intervention / Treatment: Drug: IV Furosemide; Drug: IV Furosemide and PO Metolazone; Drug: IV Furosemide and IV Acetazolamide

Detailed Description

The study will assess the efficacy and safety of three (3) different clinically prevailing diuretic regimens. All three regimens are based on furosemide, as mentioned above- a 1st line HF GL2,3 recommended and MOH registered 7 for fluid decongestion, and the two adjuvants medications are also approved as diuretics in HF patients. Better natriuresis will lead to better decongestion in CHF patients with volume overload. It is expected that the better natriuresis will lead to better decongestion, and improvement in favorable markers parameters such as NT pro BNP.

The trial will investigate treatment regimens, readily available, clinically approved ("on-label" in Israel), which can be very easily administered, through an IV infusion or IV and PO administration without additional extra testing or invasive monitoring. The setting is in an established dedicated HF day-care unit at the cardiology department of Rambam Health Campus (RMC)- a tertiary referral academic center.

The knowledge gathered in this study, could be easily adopted by every clinic or hospital in a quick manner with considerable cost-savings with regards to health care expenditure.

Importantly, this study will examine which application of existing decongestive therapies (not novel drugs), based on strong scientific reasoning, will result in a better outcome for patients. Therefore, data from the study will provide information regarding the safety and efficacy of diuretic treatment in the above-mentioned patient population.

The study intends to be a real-life study, in the manner of:

1. Conducted in an established, protocol-operated setting
2. Essential only recruitment restrictions
3. Without any additional testing to the day care standard of care
4. Have minimal or no additional expected risk for the patient (comparison between standard diuretic regimens)
5. Have very clinically meaningful endpoints.

Therefore, this study should be considered a 'Low-intervention clinical trial' as:

1. The investigational medicinal products, which are used in clinical practice and approved, have a very low-risk profile and are well-known to general cardiologists and internists worldwide.
2. According to the protocol of the clinical trial, all investigational medicinal products will be used in accordance with EU and US marketing approval according to published guidelines. Note: from commercial and supply chain reasons oral metolazone and IV acetazolamide are imported by medical institutions in Israel by means of group "29 gimel" form. Both are FDA and EU labeled for HF treatment.
3. No additional diagnostic or monitoring procedures are asked. Hence, minimal additional risk or burden to the safety of the subjects compared to normal clinical practice.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Aharon (Ronnie) Abbo, MD; Phone Number: +97147772397; Email: ro_abbo@rmc.gov.il

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Rambam MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed written informed consent must be obtained before any study assessment is performed.
2. Male or female patients 18 years of age or older
3. Confirmed Diagnosis of Heart Failure (per ESC guidelines 20212)
4. At least one sign of active congestion at recruitment: Jugular venous pressure(JVP)/Ascites/Edema/Pulmonary rales/Pleural effusion/ Lung ultrasound B lines >3 lines (at 6 sites).
5. Patient is at least on two heart failure drugs including: BB, MRA, sGLT2i, ACEI/ARB/ARNI (or has a clinical reason for its absence) and on oral diuretics for the last 30 days before study inclusion.

Exclusion Criteria:

1. History of myocardial infraction in the last 14 days prior to patient randomization.
2. History of a cardiac transplantation and/or ventricular assist device.
3. Mean blood pressure <60 mmHg at screening
4. Simultaneous use of intravenous inotropes, vasopressors or nitroprusside due to acute decompensated heart failure in the last 14 days.
5. Estimated glomerular filtration rate <20ml/min/1.73m2 at screening
6. Any circumstances where urine collection is not possible.
7. Use of renal replacement therapy or ultrafiltration 30 days prior to patient randomization.
8. Subjects who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Active Comparator: Diuretic comparison; each participant will be followed for 4 consecutive weeks. during which 3 different diuretic regimens will be given (random sequence). Last week follow up without protocol regimen.

Drug: IV Furosemide; Given over 4-hour drip using IV pump, 40mg of the 250mg will be given as a bolus; Drug: IV Furosemide and PO Metolazone; Given over 4-hour drip using IV pump, 40mg of the 250mg will be given as a bolus +5mg PO Metolazone; Drug: IV Furosemide and IV Acetazolamide; Furosemide would be given over 4-hour drip using IV pump, 40mg of the 250mg will be given as a bolus. 500mg IV Acetazolamide would be given in 100cc of saline over half an hour; Other Names: Oral Magnesium citrate 600mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sodium weight	Na Weight (Spot Na * total volume of urine)	1st week visit (time zero)
Sodium weight	Na Weight (Spot Na * total volume of urine)	1 week after 1st visit
Sodium weight	Na Weight (Spot Na * total volume of urine)	2 weeks after 1st visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Volume	Total urinary volume starting from initiation of intravenous (IV) therapy for 6 hours	1st week visit (time zero)
Urine Volume	Total urinary volume starting from initiation of intravenous (IV) therapy for 6 hours	1 week after 1st visit
Urine Volume	Total urinary volume starting from initiation of intravenous (IV) therapy for 6 hours	2 weeks after 1st visit
Rate of symptomatic hypotension events	Systolic BP <90mmhg with symptoms	A week after 1st visit
Rate of symptomatic hypotension events	Systolic BP <90mmhg with symptoms	2 weeks after 1st visit
Rate of symptomatic hypotension events	Systolic BP <90mmhg with symptoms	3 weeks after 1st visit
rate of worsening renal function events	WRF defined as a >0.3 mg/dL increase in serum Cr, or a >20% decrease in eGFR by the CKDEPI formula	A week after 1st visit
rate of worsening renal function events	WRF defined as a >0.3 mg/dL increase in serum Cr, or a >20% decrease in eGFR by the CKDEPI formula	2 weeks After 1st visit
rate of worsening renal function events	WRF defined as a >0.3 mg/dL increase in serum Cr, or a >20% decrease in eGFR by the CKDEPI formula	3 weeks after 1st visit
Rate of hyponatremia during treatment phase	Hyponatremia <133mmol/dl	A week after 1st visit
Rate of hyponatremia during treatment phase	Hyponatremia <133mmol/dl	2 weeks after 1st visit
Rate of hyponatremia during treatment phase	Hyponatremia <133mmol/dl	3 weeks after 1st visit
Rate of dyskalemia events during treatment phase	Dyskalemia defined as <3.5 or >5.6mmol/dl	A week after 1st visit
Rate of dyskalemia events during treatment phase	Dyskalemia defined as <3.5 or >5.6mmol/dl	2 weeks after 1st visit
Rate of dyskalemia events during treatment phase	Dyskalemia defined as <3.5 or >5.6mmol/dl	3 weeks after 1st visit
Rate of metabolic acidosis events requiring NaHCO3 supplements	Rate of Metabolic acidosis (requiring NaHCO3 supplements) events	A week after 1st visit
Rate of metabolic acidosis events requiring NaHCO3 supplements	Rate of Metabolic acidosis (requiring NaHCO3 supplements) events	2 weeks after 1st visit
Rate of metabolic acidosis events requiring NaHCO3 supplements	Rate of Metabolic acidosis (requiring NaHCO3 supplements) events	3 weeks after 1st visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma volume	Assessed using weight and HCT	A week after 1st visit
Change in plasma volume	Assessed using weight and HCT	2 weeks after 1st visit
Change in plasma volume	Assessed using weight and HCT	3 weeks after 1st visit
Rate of magnesium deficiency a week after treatment	Defined as Mag levels <1.6mmol/dl	A week after 1st visit
Rate of magnesium deficiency a week after treatment	Defined as Mag levels <1.6mmol/dl	2 weeks after 1st visit
Rate of magnesium deficiency a week after treatment	Defined as Mag levels <1.6mmol/dl	3 weeks after 1st visit
Change in body weight a week after each IV regimen	weight scale	A week after 1st visit
Change in body weight a week after each IV regimen	weight scale	2 weeks after 1st visit
Change in body weight a week after each IV regimen	weight scale	3 weeks after 1st visit
Change in BNP level a week after each IV treatment	Plasma Nt-ProBNP	A week after 1st visit
Change in BNP level a week after each IV treatment	Plasma Nt-ProBNP	2 weeks after 1st visit
Change in BNP level a week after each IV treatment	Plasma Nt-ProBNP	3 weeks after 1st visit
Change in decongestion achieved by change in congestion score- week after treatment	A composite score of: pedal edema, orthopnea, ultrasound evidence of pleural effusion, ascites and B-lines. each getting a rank between 0-4. total score can range from 0-16, where higher score indicates worse congestion and prognosis status.	A week after 1st visit
Change in decongestion achieved by change in congestion score- week after treatment	A composite score of: pedal edema, orthopnea, ultrasound evidence of pleural effusion, ascites and B-lines. each getting a rank between 0-4. total score can range from 0-16, where higher score indicates worse congestion and prognosis status.	2 weeks after 1st visit
Change in decongestion achieved by change in congestion score- week after treatment	A composite score of: pedal edema, orthopnea, ultrasound evidence of pleural effusion, ascites and B-lines. each getting a rank between 0-4. total score can range from 0-16, where higher score indicates worse congestion and prognosis status.	3 weeks after 1st visit

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus
• Investigators: Principal Investigator: Aharon Abbo, MD, Rambam

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2023
• Primary Completion (Actual): August 1, 2023
• Study Completion (Actual): August 24, 2023

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: June 10, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Heart Diseases; Cardiovascular Diseases; Heart Failure; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Gastrointestinal Agents; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Anticonvulsants; Cathartics; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Acetazolamide; Furosemide; Magnesium citrate; Metolazone
• Other Study ID Numbers: 0067-23-RMB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No