Chronic Heart Failure, Congestive Heart Failure, Diuretics Drug Reactions
Conditions
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.
Interventions
DRUGIV Furosemide
Given over 4-hour drip using IV pump, 40mg of the 250mg will be given as a bolus
DRUGIV 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
DRUGIV 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
Sponsors
Rambam Health Care Campus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-site, single-arm, open-label, cross-over controlled study Randomization will determine the sequence of the three (3) regimens
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sodium weight | 1st week visit (time zero) | Na Weight (Spot Na \* total volume of urine) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of symptomatic hypotension events | A week after 1st visit | Systolic BP \<90mmhg with symptoms |
| Urine Volume | 1st week visit (time zero) | Total urinary volume starting from initiation of intravenous (IV) therapy for 6 hours |
| rate of worsening renal function events | A week 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 phase | A week after 1st visit | Hyponatremia \<133mmol/dl |
| Rate of dyskalemia events during treatment phase | A week after 1st visit | Dyskalemia defined as \<3.5 or \>5.6mmol/dl |
| Rate of metabolic acidosis events requiring NaHCO3 supplements | A week after 1st visit | Rate of Metabolic acidosis (requiring NaHCO3 supplements) events |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in body weight a week after each IV regimen | A week after 1st visit | weight scale |
| Change in BNP level a week after each IV treatment | A week after 1st visit | Plasma Nt-ProBNP |
| Change in decongestion achieved by change in congestion score- week after treatment | A week after 1st visit | 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. |
| Rate of magnesium deficiency a week after treatment | A week after 1st visit | Defined as Mag levels \<1.6mmol/dl |
| Change in plasma volume | A week after 1st visit | Assessed using weight and HCT |
Countries
Israel
Outcome results
None listed