Protocol of Diuretics Use in Congestive Therapy in Heart Failure

Study Overview
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Brief Summary
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The main objective of the study is to determine if a diuretic adaptation protocol in the decompensation of chronic heart failure is more effective but also safer than the current non-protocolized practice.

Detailed Description
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Diuretics are the main treatment for congestive decompensation of chronic heart failure. For symptomatic purposes, the goal is to decrease the volume overload. In these patients, loop diuretics are used in high doses, sometimes in combination with other classes of diuretics such as thiazides to achieve synergistic, faster and more effective action, and to combat diuretic's resistance. This use, well known to cardiologists and based on a rich pharmacology, more than 40 years old, lacks robust scientific data in real life. Current studies are mainly based on patients with renal insufficiency or limited to cardio-renal syndrome. The CARRESS-H study in 2012 is one of them. The protocol for the use of diuretics from this study was included in 2017 as a benchmark in a publication of the NEJM. It therefore seems necessary to consider the exercise of this protocol in the management of the decompensation of chronic cardiac heart failure. There is, to the investigator's knowledge, no similar study to test this protocol as a real life exercise.

Official Title
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Evaluation of an Optimization Protocol for Diuretics in the Decompensation of Chronic Heart Failure: Randomized Trial in Clusters With Sequential Permutation

Conditions
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Heart Failure, Acute Heart Failure, Chronic Heart Failure

Intervention / Treatment
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* Drug: Furosemide
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients hospitalized for chronic decompensated congestive heart failure without acute pulmonary edema and acute cardiac decompensation against a background of hypertensive crisis covered under a social security program with legal capacity to give voluntary informed consent to participate in the study Exclusion Criteria: First episode of decompensated congestive heart failure Protocolized shock or hypotension (<90 mmHg blood pressure) managed or requiring nitrovasodilators or non-invasive ventilation One of the following cardiovascular pathologies: acute myocardial infarction / cardiac tamponade / aortic dissection / acute pulmonary embolism / heart transplant / ventricular assist device / acute pulmonary edema / hypertensive crisis More than 12h of intravenous diuretics administered prior to inclusion Generalized edema caused by cirrhosis or nephrotic syndrome Requiring pleural or peritoneal tap for therapeutic purposes Patient allergic or intolerant to furosemide and on long-term bumetanide use Patient in dialysis or end-stage chronic kidney disease (CKD-EPI-calculated GFR <15 mL/min/1.73m²) or acute kidney injury of known non-cardiac cause Severe hypokalemia (< 3 mmol/L) on admission Patient who is pregnant, breastfeeding, or of childbearing age not on effective contraception Adult patient safeguarded under court protection measures (guardianship, wardship, or judicial protection)

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard<br>Use of loop diuretics and thiazide diuretics leaves to the discretion of the responsible physician | Drug: Furosemide<br>* Protocol for the use of diuretics<br>Drug: Hydrochlorothiazide<br>* Protocol for the use of diuretics<br>|
| Experimental: Protocol<br>use of loop diuretics and thiazide diuretics according to the CARRESS-HF protocol developed by the Heart Failure Network | Drug: Furosemide<br>* Protocol for the use of diuretics<br>Drug: Hydrochlorothiazide<br>* Protocol for the use of diuretics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the serum creatinine level | serum creatinine | at 96 hours of admission | 
| change in weight | The weight will be measured in kilograms | at 96 hours of admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of intravenous administration of diuretics | Length of time of intravenous administration of diuretics in days | at 1 month | 
| severity of acute kidney injury during hospitalisation | Acute kidney injury requiring interruption of treatment | at 1 month | 
| Severe Hypokaliemia | Severe hypokalaemia means hypokalaemia that requiring interruption of treatment, dialysis or transfer in intensive care. | at month | 
| Number of rehospitalization for heart failure or kidney failure | Number of rehospitalization for heart failure or kidney failure | At 30 days after the date of randomisation | 
| Mortality (all cause and heart failure) | Number of death of participants | At 30 days after the date of randomisation | 
| Dose of diuretics | Comparison of diuretics dose of Furosemide and/or Thiazid diuretic. The dose will be measured on milligrams per day. | At 30 days after the date of randomisation | 
| Description and comparison of global cost between the two groups | Description and comparison of global cost between the two groups | At 30 days after the date of randomisation | 
| Estimated plasma volume change | Estimated plasma volume change captured via hemoglobin-to-hematocrit ratio (Hb/Ht) using the Strauss formula | At 30 days after the date of randomisation | 
| change in bodyweight | The weight will be measured in kilograms | at 96 hours after admission of patient | 
| Blood chemistry (serum creatinine) | serum creatinine | month 1 | 
| Blood chemistry (glomerular filtration rate) | glomerular filtration rate (GFR) estimated using the CKD-EPI equation | month 1 | 
| Blood chemistry | NT-proBNP or BNP (as available) | month 1 | 
| Blood chemistry (plasma volume estimated) | plasma volume estimated via hemoglobin-to-hematocrit ratio (Hb/Ht) | month 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Diuretics, Diuretic resistance, Loop diuretics, Furosemide