Loop Diuretic Therapy in Acutely Decompensated Heart Failure

Study Overview
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Brief Summary
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DiurHF is a prospective, multicenter, observational, study that compares continuous with intermittent infusion of furosemide in patients admitted with a diagnosis of ADHF. Previous pilot study design was planned to anticipate a larger multicenter trial able to definitively evaluate the optimal loop diuretic use strategy in patients with ADHF.

Detailed Description
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The use of intravenous loop diuretics is a cornerstone of therapy for acutely decompensated heart failure (ADHF); significant concerns have been raised regarding risks and benefits of loop diuretics, particularly about dosage and administration regimen. Recent guidelines recommend the use of these drugs to reduce left ventricular filling pressure, avoid pulmonary edema, and alleviate peripheral fluid retention. Some studies have provided guidelines for the administration of these drugs in clinical practice, but data interpretation remains challenging due to the frequent exclusion of patients with kidney disease from major ADHF clinical trials. Therefore, it is not clear if continuous infusion is better than intermittent boluses in terms of decongestion, maintenance of renal filtration function and prognosis. On the other hand, continuous administration should provide a more constant delivery of the drug into the tubule, potentially reducing these phenomena. The aim of the study is to evaluate the better loop diuretic intravenous administration in terms of renal function, congestion signs, BNP and outcome.

Official Title
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Continuous Versus Bolus Intermittent Loop Diuretic Infusion in Acutely Decompensated Heart Failure: Evaluation of Renal Function, Congestion Signs, BNP and Outcome

Conditions
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Acute Heart Failure

Intervention / Treatment
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* Drug: Continuous Furosemide Infusion
* Drug: Intermittent Furosemide Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years; Patients with diagnosis of ADHF(dyspnea, orthopnea, peripheral edema or major fatigue and at least two clinical signs including rales, hepatomegaly, pulmonary congestion on chest radiography, jugular vein dilatation, or a third heart sound); Blood BNP > 100 pg/mL; ADHF: Acute Decompensated Heart Failure; BNP: B-type Natriuretic Peptide; IV: IntraVenous; LVEF: Left Ventricular Ejection Fraction. Exclusion Criteria: Patients who receive more than 40 mg of IV furosemide; End-Stage renal disease or renal replacement therapy; Recent myocardial infarction (within thirty days of screening); Systolic blood pressure < 80 mmHg; Creatinine levels > 4 mg/dL; Patients affected by sepsis, liver diseases, inflammatory diseases or neoplastic diseases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Continuous Furosemide Infusion<br>continuous intravenous furosemide infusion | Drug: Continuous Furosemide Infusion<br>* Intravenous continuous Furosemide infusion<br>* Other names: cIV;|
| Intermittent Furosemide Infusion<br>bolus intermittent intravenous furosemide infusion | Drug: Intermittent Furosemide Infusion<br>* Intravenous bolus intermittent Furosemide Infusion<br>* Other names: iIV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac death and rehospitalization for HF | Number of participant who are affected by cardiovascular death or rehospitalization within 180 days from discharge. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| length of hospital stay (days) | evaluation of length of hospital stay (days) in the two groups | From date of randomization until the discharge (7-12 days) | 
| Inotropes agents | Need to use inotropes agents during the treatment | From date of randomization until the discharge (7-12 days) | 
| hypertonic saline solution | need to use hypertonic saline solution during the treatment | From date of randomization until the discharge (7-12 days) | 
| Acute kidney injury | changes of renal function in terms of creatinine and estimated glomerular filtration rate (eGFR) comparing continuous vs intermittent administration | From date of randomization until the discharge (7-12 days) | 
| Body weight changes | Body weight changes in two groups from the admission to discharge | from admission to discharge (7-12 days) | 
| Diuresis | mean urine output in two groups from the admission to discharge | from admission to discharge (7-12 days) | 
| BNP changes | mean paired changes of B-type natriuretic peptide (BNP) in the two groups during hospitalization. | From date of randomization until the discharge (7-12 days) | 
| BUN changes | mean paired changes of blood urea nitrogen (BUN) in the two groups during hospitalization. | From date of randomization until the discharge (7-12 days) | 
| Reduction of edema | Evaluation of edema regression (or not) after treatment in the two groups. | From date of randomization until the discharge (7-12 days) | 
| Reduction of dyspnea | Evaluation of dyspnea scale reduction (or not) after treatment in the two groups. | From date of randomization until the discharge (7-12 days) | 
| Regression of pulmonary congestion | Evaluation of pulmonary congestion regression (or not) after treatment in the two groups, considering Chest X-ray at admission and at discharge | From date of randomization | 
| Diuretic efficiency: (Weight loss/days of infusion)/ (Mean daily furosemide dosage/40 mg of furosemide) | Evaluation of persistence of congestion (or not) and incidence of AKI (or not) according to quartiles of diuretic efficiency. | From hospital admission until the discharge (7-12 days) | 
| High (> 125 mg/die) versus low (<125 mg/die) intravenous diuretic dosage | Number of patients with high in-hospital diuretic dosage who were affected by adverse outcome. | 180 days | 
| Diuretic efficiency: (Weight loss/days of infusion)/ (Mean daily furosemide dosage/40 mg of furosemide) | Number of patients (according quartiles of diuretic efficiency) who were affected by adverse outcome. | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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loop diuretic, heart failure, renal dysfunction, congestion signs, BNP