PREVENTION OF WORSENING RENAL FUNCTION OF INTRAVENUS ALBUMIN IN HEART FAILURE PATIENTS

HUMAN ALBUMIN IN HEART FAILURE - DIORASIS TRIAL

Patients hospitalized for acute decompensation of CHF are usually complicated by worsening renal function (WRF) which leads to diuretic resistance and inadequate decongestion as well as poor prognosis. WRF has been attributed to a reflex renal vasoconstriction elicited by intravascular volume depletion during brisk diuresis. The investigators hypothesize that CHF patients with hepatic dysfunction are more prone to WRF due to poor albumin production. This sub-group of CHF patients may benefit more (increased diuretic efficacy and protected against worsening renal function) by the use of IV loop diuretics in combination with an intravascular volume expander such as IV Human Albumin.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; With Decompensation; Diuretics Drug Reactions; Albumin; Double
• Intervention / Treatment: Drug: Human albumin

Detailed Description

Acute decompensation of chronic heart failure (CHF) warranting hospital admission, defined as diagnosed on the basis of the presence of at least one symptom (dyspnea, orthopnea, paroxysmal nocturnal dyspnea, weight gain, worsening functional class or edema) and one sign (rales, peripheral edema, ascites, increased jugular vein pressure, hepatomegaly, third heart sound gallop or pulmonary vascular congestion on chest radiography) of heart failure plus laboratory or imaging evidence of hepatic dysfunction at randomization

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: MARIOS-VASILEIOS A KOUTROULOS; Phone Number: +30 6942862493; Email: mvkoutroulos@gmail.com
• Study Contact Backup: Name: ANARGYROS TSALGKIDIS; Phone Number: 6940926983; Email: anargyrost@gmail.com

Study Locations

• Greece
  • Evros
    • Alexandroupolis, Evros, Greece, 68100
      • Recruiting
      • DUThrace Cardiology Department
      • Contact: Marios Vasileios Β Koutroulos; Phone Number: 6942862493; Email: mvkoutroulos@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age over 18 yrs
2. acute decompensation of CHF
3. evidence of hepatic dysfunction by laboratory biochemical measurements or imaging (liver ultrasonography)
4. history of CHF with previous use of an oral loop diuretic
5. anticipated need for IV diuretic therapy for at least 72 hours

There is no pre-specified inclusion criterion with respect to ejection fraction

Exclusion Criteria:

1. hemodynamic collapse (at least one of the following: systolic blood pressure (BP) < 90 mmHg, or BP drop by >= 40 mmHg for >= 15 min, with end-organ hypoperfusion; need for inotropes (except of digoxin); need for cardiopulmonary resuscitation).
2. hepatic dysfunction of other than cardiac etiology
3. severe anemia (Hb<8 g/dL)
4. uncontrolled hypertension or hypertensive emergency/urgency
5. pulmonary edema or pulmonary congestion necessitating use of IV vasodilators
6. serum creatinine > 3 mg/dL or glomerular filtration rate (GFR) < 30 ml/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IV Human Albumin + IV Furosemide; Continuous slow IV infusion of Human Albumin plus IV Furosemide	Drug: Human albumin; Experimental intervention (Group A): Continuous slow IV infusion of Human Albumin, based on diuresis-adjusted dosing, not later than 30 minutes after randomisation and not later than 2 hours after admission. Concomitant continuous slow IV infusion of diuretics (furosemide) based on body weight- and diuresis-adjusted dosing. Control intervention (Group B): Continuous slow IV infusion of diuretics (furosemide), based on body weight - and diuresis-adjusted dosing. Experimental intervention (Human Albumin) is off-label treatment for patients with acute decompensation of CHF in Greece. Control intervention (IV diuretic therapy) is on-label treatment for acute decompensation CHF in Greece.
Placebo Comparator: IV Furosemide alone; Continuous slow IV infusion of Furosemide	Drug: Human albumin; Experimental intervention (Group A): Continuous slow IV infusion of Human Albumin, based on diuresis-adjusted dosing, not later than 30 minutes after randomisation and not later than 2 hours after admission. Concomitant continuous slow IV infusion of diuretics (furosemide) based on body weight- and diuresis-adjusted dosing. Control intervention (Group B): Continuous slow IV infusion of diuretics (furosemide), based on body weight - and diuresis-adjusted dosing. Experimental intervention (Human Albumin) is off-label treatment for patients with acute decompensation of CHF in Greece. Control intervention (IV diuretic therapy) is on-label treatment for acute decompensation CHF in Greece.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of symptoms	Patient's global assessment of symptoms, measured with the use of a visual-analogue scale (VAS) and quantified as the area under the curve (AUC) of serial assessments.	From baseline to 72 hours.
Change in the serum creatinine level	Change in the serum creatinine level	From baseline to 72 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported dyspnea	Patient-reported dyspnea (as assessed with the use of a VAS and quantified as the AUC of serial assessments)	From baseline to 72 hours.
Changes in body weight	Changes in body weight	From baseline to 72 hours.
Length of stay	Length of stay	From baseline to discharge.
The composite of death, rehospitalization, escalation in treatment or an emergency room visit within 180 days.	The composite of death, rehospitalization, escalation in treatment or an emergency room visit within 180 days.	From baseline to 180 days from discharge.
Net fluid loss	Net fluid loss	From baseline to 72 hours

Collaborators and Investigators

• Sponsor: Democritus University of Thrace
• Investigators: Principal Investigator: MARIOS VASILEIOS KOUTROULOS, University Hospital of Alexandroupolis

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 11, 2026

Study Registration Dates

• First Submitted: March 29, 2023
• First Submitted That Met QC Criteria: October 4, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: October 4, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Heart Failure; Furosemide; Human Albumin
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Heart Diseases; Cardiovascular Diseases; Heart Failure; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: 6/ 29.2.2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No