Diuretic Response in Advanced Heart Failure: Bolus Intermittent vs Continuous INfusion (DRAIN)

Diuretic Treatment in High Risk Decompensated Advanced Heart Failure. Bolus Intermittent Versus Continuous Infusion of Furosemide: a Randomized Controlled Trial.

Loop diuretics are the main therapy for decongestion of patients with advanced acute heart failure. However, these patients often develop diuretic-resistance or even diuretic-refractoriness. In order to overcome such resistance to diuretic, the clinician can increase the dose of furosemide, or change the way of administration (continuous infusion versus boluses) or associate a different class of diuretics (thiazide diuretics, K+-sparing diuretics) up to the addition of low doses of inotropic agents to improve renal perfusion. At the present time there is no evidence in literature in advanced acute heart failure patients about the superiority of the treatment with furosemide in continuous infusion or in intermittent boluses. The aim of the study was to evaluate the efficacy of furosemide in boluses versus continuous infusion in advanced acute heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure NYHA Class III; Heart Failure NYHA Class IV
• Intervention / Treatment: Drug: Loop Diuretics

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • To
    • Torino, To, Italy, 10126
      • Simone Frea

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:

• Advanced heart failure
• WET ≥ 12
• Systolic blood pressure ≤ 110 mmHg
• Serum sodium ≤ 135 mEq/L
• Left systolic ventricular insufficiency (FE < 35%) note for at least 6 months
• Class NYHA III-IV despite medical treatment maximal

Exclusion Criteria:

• Acute coronary syndrome
• Shock cardiogenic
• Chronic renal failure stage V

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continuous infusion of loop diuretics; Furosemide continuous infusion: 125 or 250 mg die	Drug: Loop Diuretics; intravenous administration of diuretics; Other Names: furosemide
Active Comparator: Intermittent infusion of loop diuretics; Furosemide bolus intermittent: 125 or 250 mg die	Drug: Loop Diuretics; intravenous administration of diuretics; Other Names: furosemide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Freedom from congestion	72 hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Worsening of renal function	Increase in creatinine value > 0.3 mg/dl or increase > 1.5 times	72 hours after randomization
Worsening or persistent HF at 72 h	Need to increase the dose of inotropes or diuretics	72 hours after randomization
Change in body weight		72 hours after randomization
Laboratory data variations in NTproBNP		72 hours after randomization
Treatment failure	Composed by the following events: persistence of congestion, need to increase diuretic treatment, need of renal replacement treatment	72 hours after randomization
Weight differences based on diuretic dose unity		72 hours after randomization

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Investigators: Principal Investigator: Simone Frea, MD, A.O.U. Città della Salute e Della Scienza di Torino

Publications and helpful links

General Publications

• Frea S, Pidello S, Volpe A, Canavosio FG, Galluzzo A, Bovolo V, Camarda A, Golzio PG, D'Ascenzo F, Bergerone S, Rinaldi M, Gaita F. Diuretic treatment in high-risk acute decompensation of advanced chronic heart failure-bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial. Clin Res Cardiol. 2020 Apr;109(4):417-425. doi: 10.1007/s00392-019-01521-y. Epub 2019 Jun 29.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2013
• Primary Completion (Actual): December 22, 2017
• Study Completion (Actual): December 22, 2017

Study Registration Dates

• First Submitted: June 18, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (Actual): July 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 19, 2018
• Last Update Submitted That Met QC Criteria: July 9, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Furosemide; Diuretics; Sodium Potassium Chloride Symporter Inhibitors
• Other Study ID Numbers: DRAIN trial

Drug and device information, study documents

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