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

Phase 4
Completed
Conditions
Chronic Heart Failure
Congestive Heart Failure
Diuretics Drug Reactions
Interventions
Registration Number
NCT05904808
Lead Sponsor
Rambam Health Care Campus
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
42
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Diuretic comparisonIV Furosemideeach 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.
Diuretic comparisonIV Furosemide and PO Metolazoneeach 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.
Diuretic comparisonIV Furosemide and IV Acetazolamideeach 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.
Primary Outcome Measures
NameTimeMethod
Sodium weight2 weeks after 1st visit

Na Weight (Spot Na \* total volume of urine)

Secondary Outcome Measures
NameTimeMethod
Urine Volume2 weeks after 1st visit

Total urinary volume starting from initiation of intravenous (IV) therapy for 6 hours

Rate of symptomatic hypotension events3 weeks after 1st visit

Systolic BP \<90mmhg with symptoms

rate of worsening renal function events3 weeks after 1st visit

WRF defined as a \>0.3 mg/dL increase in serum Cr, or a \>20% decrease in eGFR by the CKDEPI formula

Rate of hyponatremia during treatment phase3 weeks after 1st visit

Hyponatremia \<133mmol/dl

Rate of dyskalemia events during treatment phase3 weeks after 1st visit

Dyskalemia defined as \<3.5 or \>5.6mmol/dl

Rate of metabolic acidosis events requiring NaHCO3 supplements3 weeks after 1st visit

Rate of Metabolic acidosis (requiring NaHCO3 supplements) events

Trial Locations

Locations (1)

Rambam MC

🇮🇱

Haifa, Israel

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