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Early Sequential Nephron Blockade in Acute Heart Failure Patients: A Randomised, Controlled Study (NEB-HF)

Primary Purpose

Acute Heart Failure, Acute Kidney Injury

Status

Unknown status

Phase

Phase 3

Locations

Thailand

Study Type

Interventional

Intervention

Spironolactone or hydrochlorothiazide

Placebo

About this trial

This is an interventional treatment trial for Acute Heart Failure focused on measuring Acute heart failure, Diuretic resistance, Sequential nephron blockade, Diuretic combination

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Furosemide with spironolactone or hydrochlorothiazide

Furosemide with placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Urine volume

Total urine volume after randomisation

Secondary Outcome Measures

Urine volume

Total urine volume after randomization

Body weight

Changes of patient's body weight

Length of hospital admission

Number of days that patients need to stay in the hospital

Furosemide dose

Total dosage of intravenous furosemide

Levels of B-type atrial natriuretic peptide (BNP)

levels of pro-BNP

Number of participants with adverse events

All adverse events during hospital admission

Dyspnea score assessed by visual analogue scale

The scale is between 0 and 100. The higher scale represents lower level of dyspnea

Full Information

NCT ID

NCT04465123

First Posted

July 6, 2020

Last Updated

August 16, 2020

Sponsor

Chiang Mai University

1. Study Identification

Unique Protocol Identification Number

NCT04465123

Brief Title

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

Acronym

NEB-HF

Official Title

Furosemide With Early Sequential Nephron Blockade Versus Furosemide Alone in Acute Heart Failure Patients With Furosemide-guided Diuretic Resistance: A Double-blinded, Randomized, Placebo-controlled Study

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Unknown status

Study Start Date

August 13, 2020 (Actual)

Primary Completion Date

July 31, 2022 (Anticipated)

Study Completion Date

December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chiang Mai University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Heart Failure, Acute Kidney Injury

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Furosemide with spironolactone or hydrochlorothiazide

Arm Type

Experimental

Arm Description

Arm Title

Furosemide with placebo

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Spironolactone or hydrochlorothiazide

Other Intervention Name(s)

Aldactone, HCTZ, Thiazide

Intervention Description

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

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Urine volume

Description

Total urine volume after randomisation

Time Frame

72 hours

Secondary Outcome Measure Information:

Title

Urine volume

Description

Total urine volume after randomization

Time Frame

24 and 48 hours

Title

Body weight

Description

Changes of patient's body weight

Time Frame

72 hours after randomisation

Title

Length of hospital admission

Description

Number of days that patients need to stay in the hospital

Time Frame

During hospital admission period

Title

Furosemide dose

Description

Total dosage of intravenous furosemide

Time Frame

72 hours after randomisation

Title

Levels of B-type atrial natriuretic peptide (BNP)

Description

levels of pro-BNP

Time Frame

72 hours and 7 days after randomisation

Title

Number of participants with adverse events

Description

All adverse events during hospital admission

Time Frame

During hospital admission

Title

Dyspnea score assessed by visual analogue scale

Description

The scale is between 0 and 100. The higher scale represents lower level of dyspnea

Time Frame

At randomization, and 6, 12, 24, 48 and 72 hours after randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Kajohnsak Noppakun, MD

Phone

+66815953465

kajohnsak.noppakun@cmu.ac.th

First Name & Middle Initial & Last Name or Official Title & Degree

Tiranun Suriya, RN

Phone

+66818812106

tingsuri@hotmail.co.th

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kajohnsak Noppakun, MD

Organizational Affiliation

Instructor, Division of Nephrology, Department of Internal Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Chiang Mai

ZIP/Postal Code

50200

Country

Thailand

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kajohnsak Noppakun, MD

Phone

+66815953465

kajohnsak.noppakun@cmu.ac.th

First Name & Middle Initial & Last Name & Degree

Tiranun Suriya, RN

Phone

+66818812106

tingsuri@hotmail.co.th

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Request for individual participant data (IPD) has to be submitted to the Institutional Review Board (IRB) of Faculty of Medicine, Chiang Mai University, Chiang Mai, THAILAND.

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

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