Early Sequential Nephron Blockade in Acute Heart Failure Patients: A Randomised, Controlled Study

NCT04465123 | Unknown Phase 3

• 1 other identifier: MED-2563-07080 (2)
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to demonstrate the efficacy of sequential nephron blockade by adding hydrochlorothiazide or spironolactone on intravenous furosemide compared to intravenous furosemide alone in the treatments of volume overload in patients with acute heart failure who have diuretic resistance from furosemide stress test.

Conditions

Acute Heart Failure; Acute Kidney Injury

Keywords

Acute heart failure; Diuretic resistance; Sequential nephron blockade; Diuretic combination

Outcome Measures

Primary Outcomes (1)

• Urine volume

  Total urine volume after randomisation

  72 hours

Secondary Outcomes (7)

• Urine volume

  24 and 48 hours

• Body weight

  72 hours after randomisation

• Length of hospital admission

  During hospital admission period

• Furosemide dose

  72 hours after randomisation

• Levels of B-type atrial natriuretic peptide (BNP)

  72 hours and 7 days after randomisation

Study Arms (2)

Furosemide with spironolactone or hydrochlorothiazide

EXPERIMENTAL

IV furosemide dosage will be adjusted according to the protocol as follows. Level 1: previous oral furosemide dose ≤80 mg/day; furosemide 80 mg IV bolus every 6 hours Level 2: previous oral furosemide dose 81-160 mg/day; furosemide 160 mg IV bolus every 6 hours Level 3: previous oral furosemide dose \>160 mg/day; furosemide 250 mg IV bolus every 6 hours Furosemide dosage will be adjusted to keep urine output between 3,000 and 5,000 ml/day and \>600 ml during 6 hours after furosemide administration. If the urine output \<3,000 ml/day or \<600 ml per 6 hours, furosemide dosage will be increase 1-level up per protocol above. If the urine output \>5,000 ml/day, furosemide dosage will be reduced 1-level down per protocol above. Patients will be received spironolactone or hydrochlorothiazide in combination with intravenous furosemide according to patients' serum potassium levels.

Drug: Spironolactone or hydrochlorothiazide

Furosemide with placebo

ACTIVE COMPARATOR

IV furosemide dosage will be adjusted according to the pre-defined protocol as shown in the experimental group. Patients will be received spironolactone placebo or hydrochlorothiazide placebo in combination with intravenous furosemide according to patients' serum potassium levels.

Drug: Placebo

Interventions

Spironolactone or hydrochlorothiazide DRUG

Patients will be received spironolactone or hydrochlorothiazide in combination with intravenous furosemide according to patients' serum potassium levels. If serum potassium levels ≤4 mEq/L, patients will be received spironolactone 100 mg every 12 hour for 72 hours. If serum potassium levels \>4 mEq/L, patients will be received hydrochlorothiazide 50 mg every 12 hour for 72 hours.

Also known as: Aldactone, HCTZ, Thiazide

Furosemide with spironolactone or hydrochlorothiazide

Placebo DRUG

Patients will be received spironolactone placebo or hydrochlorothiazide placebo in combination with intravenous furosemide according to patients' serum potassium levels. If serum potassium levels ≤4 mEq/L, patients will be received spironolactone placebo every 12 hour for 72 hours. If serum potassium levels \>4 mEq/L, patients will be received hydrochlorothiazide placebo every 12 hour for 72 hours.

Furosemide with placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Diagnosis of acute heart failure which is defined by 2 of the 3 following features: ≥2+ leg edema, jugular venous pressure \>10 cm from physical examination or central venous pressure \>10 mmHg, and bilateral pulmonary edema or bilateral pleural effusion from chest radiography
• Patients consent to participate into the study

You may not qualify if:

• Patients who receive furosemide ≥500 mg/day or hydrochlorothiazide ≥100 mg/day or spironolactone ≥100 mg/day or tolvaptan of any doses
• Patients who have systolic blood pressure \<100 mmHg or who need vasoactive drugs inotropic agents (except dobutamine)
• Patients with intravascular volume depletion from clinical evaluation
• Patients with chronic kidney disease stage 5 (estimated glomerular filtration rate \<15 ml/min/1.73 m2) or patients who receive maintenance dialysis
• Patients who require renal replacement therapy at the time of admission
• Patients whom diagnosed hypertrophic obstructive cardiomyopathy, severe valvular stenosis or complex congenital heart disease
• Patients with sepsis or systemic infection
• Pregnant women
• Patients who have history of furosemide, spironolactone or hydrochlorothiazide allergy

Sponsors & Collaborators

• Chiang Mai University: lead

Study Sites (1)

Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University

Chiang Mai, 50200, Thailand

RECRUITING

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

buthiazide, spironolactone drug combination; Spironolactone; Hydrochlorothiazide; Thiazides

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kajohnsak Noppakun, MD

  Instructor, Division of Nephrology, Department of Internal Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kajohnsak Noppakun, MD

CONTACT

+66815953465; kajohnsak.noppakun@cmu.ac.th

Tiranun Suriya, RN

CONTACT

+66818812106; tingsuri@hotmail.co.th

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 9, 2020
• Study Start: August 13, 2020
• Primary Completion: July 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 18, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)