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

August 16, 2020 updated by: Kajohnsak Noppakun, Chiang Mai University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Chiang Mai, Thailand, 50200
        • Recruiting
        • Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 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.
Drug: 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.

Other Names:
  • Aldactone
  • HCTZ
  • Thiazide
ACTIVE_COMPARATOR: 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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Urine volume
Time Frame: 72 hours
Total urine volume after randomisation
72 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Urine volume
Time Frame: 24 and 48 hours
Total urine volume after randomization
24 and 48 hours
Body weight
Time Frame: 72 hours after randomisation
Changes of patient's body weight
72 hours after randomisation
Length of hospital admission
Time Frame: During hospital admission period
Number of days that patients need to stay in the hospital
During hospital admission period
Furosemide dose
Time Frame: 72 hours after randomisation
Total dosage of intravenous furosemide
72 hours after randomisation
Levels of B-type atrial natriuretic peptide (BNP)
Time Frame: 72 hours and 7 days after randomisation
levels of pro-BNP
72 hours and 7 days after randomisation
Number of participants with adverse events
Time Frame: During hospital admission
All adverse events during hospital admission
During hospital admission
Dyspnea score assessed by visual analogue scale
Time Frame: At randomization, and 6, 12, 24, 48 and 72 hours after randomization
The scale is between 0 and 100. The higher scale represents lower level of dyspnea
At randomization, and 6, 12, 24, 48 and 72 hours after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chiang Mai University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 13, 2020

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2022

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 6, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2020

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 9, 2020

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 18, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MED-2563-07080 (2)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Dietary Supplements

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