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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.
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:
Therefore, this study should be considered a 'Low-intervention clinical trial' as:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diuretic comparison | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IV Furosemide | Drug | Given over 4-hour drip using IV pump, 40mg of the 250mg will be given as a bolus |
|
| 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 |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Aharon Abbo, MD | Rambam Health Care Campus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rambam MC | Haifa | 3109601 | Israel |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | May 20, 2023 | Jun 1, 2023 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D005665 | Furosemide |
| D000086 | Acetazolamide |
| C110422 | magnesium citrate |
| ID | Term |
|---|---|
| D013424 | Sulfanilamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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Single-site, single-arm, open-label, cross-over controlled study Randomization will determine the sequence of the three (3) regimens
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| IV Furosemide and PO Metolazone | Drug | 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 | Drug | 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 |
|
|
| 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 |
| 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 |
| D000814 |
| Aniline Compounds |
| D000588 | Amines |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D013830 | Thiadiazoles |
| D013844 | Thiazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |