Protocol of Diuretics Use in Congestive Therapy in Heart Failure (ProDUCT-HF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Chronic Heart Failure; Acute Heart Failure
• Intervention / Treatment: Drug: Furosemide; Drug: Hydrochlorothiazide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Annecy, France
    • Recruiting
    • CH Annecy
    • Sub-Investigator: Mathieu CHACORNAC
  • Clermont-Ferrand, France, 63003
    • Recruiting
    • CHU Clermont-Ferrand
    • Principal Investigator: Guillaume CLERFOND
    • Sub-Investigator: Romain ESCHALIER
    • Sub-Investigator: Pascal MOTREFF
  • Grenoble, France
    • Recruiting
    • CHU de Grenoble
    • Sub-Investigator: Gérald VANZETTO
  • Issoire, France
    • Recruiting
    • Ch Issoire
    • Sub-Investigator: Youssef NAHLI
  • Le Puy-en-Velay, France
    • Recruiting
    • CH PUY
    • Sub-Investigator: Olivier DE TAURIAC
  • Lyon, France
    • Recruiting
    • CH Lyon sud
    • Sub-Investigator: Brahim HARBAOUI
  • Lyon, France, 69300
    • Recruiting
    • Infirmerie Protestante de Lyon
    • Sub-Investigator: Salim MADI
  • Moulins, France
    • Recruiting
    • CH Moulins
    • Sub-Investigator: Hassan BARAKE
  • Riom, France
    • Recruiting
    • CH RIOM
    • Sub-Investigator: Laurence FLORK

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Hospices Civils de Lyon; University Hospital, Grenoble; Hôpital de la Croix-Rousse; CH Annecy Genevois; CH Puy en Velay; CH Moulins-Yzeure; CH Riom; Infirmerie Protestante de Lyon; CH Issoire

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: February 22, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Actual): April 15, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Heart Failure; Diuretics; Furosemide; Diuretic resistance; Loop diuretics
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Hydrochlorothiazide; Furosemide
• Other Study ID Numbers: CHU-428; 2018-A02971-54 (Other Identifier: 2018-A02971-54)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No