Acute Heart FailurePhase 3NEB-HFNCT04465123
Early Sequential Nephron Blockade in Acute Heart Failure Patients: A Randomised, Controlled Study
A Phase 3 study testing Spironolactone or hydrochlorothiazide in people with Acute Heart Failure and Acute Kidney Injury, run by Chiang Mai University at 1 site in Thailand.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Heart Failure, Acute Kidney Injury
- What is being tested?
- Spironolactone or hydrochlorothiazide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteThailand
- Study dates
- 13 Aug 2020to 31 Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- Patients with sepsis or systemic infection
- Pregnant women
- Patients who have history of furosemide, spironolactone or hydrochlorothiazide allergy
Trial locations and contacts
1 site in 1 country.
Thailand1 site, 1 recruiting
- Recruiting
Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University
Chiang Mai, 50200
Kajohnsak Noppakun, MD, +66815953465, kajohnsak.noppakun@cmu.ac.th
Tiranun Suriya, RN, +66818812106, tingsuri@hotmail.co.th
About this study
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
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.
Read the 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
- Being tested
- Spironolactone or hydrochlorothiazide, Placebo
- Keywords
- Acute heart failure, Diuretic resistance, Sequential nephron blockade, Diuretic combination
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spironolactone or hydrochlorothiazideDrug
Also called Aldactone, HCTZ, Thiazide
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urine volume
Total urine volume after randomisation
Measured: 72 hours
Secondary outcomes (7)
Urine volume
Total urine volume after randomization
Measured: 24 and 48 hours
Body weight
Changes of patient's body weight
Measured: 72 hours after randomisation
Length of hospital admission
Number of days that patients need to stay in the hospital
Measured: During hospital admission period
Furosemide dose
Total dosage of intravenous furosemide
Measured: 72 hours after randomisation
Levels of B-type atrial natriuretic peptide (BNP)
levels of pro-BNP
Measured: 72 hours and 7 days after randomisation
Number of participants with adverse events
All adverse events during hospital admission
Measured: 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
Measured: At randomization, and 6, 12, 24, 48 and 72 hours after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start13 Aug 2020
- Primary completion31 Jul 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chiang Mai University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kajohnsak Noppakun, Chiang Mai University
- Investigators
- Kajohnsak Noppakun, MD, Principal investigator, Instructor, Division of Nephrology, Department of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04465123
- Sponsor's protocol ID
- MED-2563-07080 (2)
- Acronym
- NEB-HF
- Status last verified
- Aug 2020
- First submitted
- 6 Jul 2020
- Last updated
- 18 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04465123
- Acronym / sponsor ID
- NEB-HF / MED-2563-07080 (2)
- Conditions
- Acute Heart Failure, Acute Kidney Injury
- Keywords
- Acute heart failure, Diuretic resistance, Sequential nephron blockade, Diuretic combination
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Chiang Mai UniversityUniversity, hospital or other
- Study start
- 13 Aug 2020 (actual)
- Primary completion
- 31 Jul 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 9 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Furosemide with spironolactone or hydrochlorothiazide | Experimental | Drug: Spironolactone or hydrochlorothiazideIV 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. |
| Furosemide with placebo | Active comparator | Drug: PlaceboIV 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spironolactone or hydrochlorothiazideAlso: Aldactone, HCTZ, ThiazidePatients 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. | Drug | Furosemide with spironolactone or hydrochlorothiazide |
| PlaceboPatients 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. | Drug | Furosemide with placebo |
Primary outcome
Urine volume
Time frame: 72 hours
Total urine volume after randomisation
7 secondary outcomes
Urine volume
Time frame: 24 and 48 hours
Body weight
Time frame: 72 hours after randomisation
Length of hospital admission
Time frame: During hospital admission period
Furosemide dose
Time frame: 72 hours after randomisation
Levels of B-type atrial natriuretic peptide (BNP)
Time frame: 72 hours and 7 days after randomisation
Number of participants with adverse events
Time frame: During hospital admission
Dyspnea score assessed by visual analogue scale
Time frame: At randomization, and 6, 12, 24, 48 and 72 hours after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2020.
- Individual participant dataSharing planned: No. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kajohnsak Noppakun, MD principal investigator
Instructor, Division of Nephrology, Department of Internal Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Spironolactone or hydrochlorothiazide in people with Acute Heart Failure and Acute Kidney Injury, run by Chiang Mai University at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kajohnsak Noppakun, MD (+66815953465, kajohnsak.noppakun@cmu.ac.th), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urine volume (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2020.