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

NCT ID: NCT04465123

Last Updated: 2020-08-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-13
• Study Completion Date: 2022-12-31

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.

Detailed Description

This study is a randomised, double-blinded, double-dummy, placebo-controlled study to demonstrate the efficacy of oral hydrochlorothiazide or spironolactone in combination with intravenous furosemide compared to intravenous furosemide in combination with placebo. Dosage of intravenous furosemide will be adjusted according to pre-defined protocol. The primary outcome is urine volume during 72 hours after randomisation.

Conditions

Acute Heart Failure; Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Furosemide with spironolactone or hydrochlorothiazide

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.

Group Type: EXPERIMENTAL

Spironolactone or hydrochlorothiazide

Intervention Type: 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.

Furosemide with placebo

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.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

Spironolactone or hydrochlorothiazide

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Aldactone; HCTZ; Thiazide

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiang Mai University

OTHER

Sponsor Role: lead

Responsible Party

Kajohnsak Noppakun

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kajohnsak Noppakun, MD

Role: PRINCIPAL_INVESTIGATOR

Instructor, Division of Nephrology, Department of Internal Medicine

Locations

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

Chiang Mai, , Thailand

Site Status: RECRUITING

Countries

Thailand

Central Contacts

Kajohnsak Noppakun, MD

Role: CONTACT

kajohnsak.noppakun@cmu.ac.th

+66815953465

Tiranun Suriya, RN

Role: CONTACT

tingsuri@hotmail.co.th

+66818812106

Facility Contacts

Kajohnsak Noppakun, MD

Role: primary

kajohnsak.noppakun@cmu.ac.th

+66815953465

Tiranun Suriya, RN

Role: backup

tingsuri@hotmail.co.th

+66818812106

Other Identifiers

MED-2563-07080 (2)

Identifier Type: -

Identifier Source: org_study_id