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

Congestive Heart Failure Clinical Trial

— DEA-HF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05904808
• Other study ID #: 0067-23-RMB
• Status: Completed
• Phase: Phase 4
• Start date: April 19, 2023
• Est. completion date: August 24, 2023

Study information

• Verified date: May 2024
• Source: Rambam Health Care Campus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: August 24, 2023
• Est. primary completion date: August 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Heart Failure
• Congestive Heart Failure
• Diuretics Drug Reactions
• Drug-Related Side Effects and Adverse Reactions
• Heart Failure

Intervention

Drug:
• IV Furosemide
Given over 4-hour drip using IV pump, 40mg of the 250mg will be given as a bolus
• 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
• 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

Locations

Country	Name	City	State
Israel	Rambam MC	Haifa

Sponsors (1)

Lead Sponsor	Collaborator
Rambam Health Care Campus

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in plasma volume	Assessed using weight and HCT	A week after 1st visit
Other	Change in plasma volume	Assessed using weight and HCT	2 weeks after 1st visit
Other	Change in plasma volume	Assessed using weight and HCT	3 weeks after 1st visit
Other	Rate of magnesium deficiency a week after treatment	Defined as Mag levels <1.6mmol/dl	A week after 1st visit
Other	Rate of magnesium deficiency a week after treatment	Defined as Mag levels <1.6mmol/dl	2 weeks after 1st visit
Other	Rate of magnesium deficiency a week after treatment	Defined as Mag levels <1.6mmol/dl	3 weeks after 1st visit
Other	Change in body weight a week after each IV regimen	weight scale	A week after 1st visit
Other	Change in body weight a week after each IV regimen	weight scale	2 weeks after 1st visit
Other	Change in body weight a week after each IV regimen	weight scale	3 weeks after 1st visit
Other	Change in BNP level a week after each IV treatment	Plasma Nt-ProBNP	A week after 1st visit
Other	Change in BNP level a week after each IV treatment	Plasma Nt-ProBNP	2 weeks after 1st visit
Other	Change in BNP level a week after each IV treatment	Plasma Nt-ProBNP	3 weeks after 1st visit
Other	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
Other	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
Other	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
Primary	Sodium weight	Na Weight (Spot Na * total volume of urine)	1st week visit (time zero)
Primary	Sodium weight	Na Weight (Spot Na * total volume of urine)	1 week after 1st visit
Primary	Sodium weight	Na Weight (Spot Na * total volume of urine)	2 weeks after 1st visit
Secondary	Urine Volume	Total urinary volume starting from initiation of intravenous (IV) therapy for 6 hours	1st week visit (time zero)
Secondary	Urine Volume	Total urinary volume starting from initiation of intravenous (IV) therapy for 6 hours	1 week after 1st visit
Secondary	Urine Volume	Total urinary volume starting from initiation of intravenous (IV) therapy for 6 hours	2 weeks after 1st visit
Secondary	Rate of symptomatic hypotension events	Systolic BP <90mmhg with symptoms	A week after 1st visit
Secondary	Rate of symptomatic hypotension events	Systolic BP <90mmhg with symptoms	2 weeks after 1st visit
Secondary	Rate of symptomatic hypotension events	Systolic BP <90mmhg with symptoms	3 weeks after 1st visit
Secondary	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
Secondary	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
Secondary	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
Secondary	Rate of hyponatremia during treatment phase	Hyponatremia <133mmol/dl	A week after 1st visit
Secondary	Rate of hyponatremia during treatment phase	Hyponatremia <133mmol/dl	2 weeks after 1st visit
Secondary	Rate of hyponatremia during treatment phase	Hyponatremia <133mmol/dl	3 weeks after 1st visit
Secondary	Rate of dyskalemia events during treatment phase	Dyskalemia defined as <3.5 or >5.6mmol/dl	A week after 1st visit
Secondary	Rate of dyskalemia events during treatment phase	Dyskalemia defined as <3.5 or >5.6mmol/dl	2 weeks after 1st visit
Secondary	Rate of dyskalemia events during treatment phase	Dyskalemia defined as <3.5 or >5.6mmol/dl	3 weeks after 1st visit
Secondary	Rate of metabolic acidosis events requiring NaHCO3 supplements	Rate of Metabolic acidosis (requiring NaHCO3 supplements) events	A week after 1st visit
Secondary	Rate of metabolic acidosis events requiring NaHCO3 supplements	Rate of Metabolic acidosis (requiring NaHCO3 supplements) events	2 weeks after 1st visit
Secondary	Rate of metabolic acidosis events requiring NaHCO3 supplements	Rate of Metabolic acidosis (requiring NaHCO3 supplements) events	3 weeks after 1st visit