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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04465123
Recruitment Status : Recruiting
First Posted : July 9, 2020
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Kajohnsak Noppakun, Chiang Mai University

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.

Condition or disease Intervention/treatment Phase
Acute Heart Failure Acute Kidney Injury Drug: Spironolactone or hydrochlorothiazide Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : July 31, 2020
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
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.





Primary Outcome Measures :
  1. Urine volume [ Time Frame: 72 hours ]
    Total urine volume after randomisation


Secondary Outcome Measures :
  1. Urine volume [ Time Frame: 24 and 48 hours ]
    Total urine volume after randomization

  2. Body weight [ Time Frame: 72 hours after randomisation ]
    Changes of patient's body weight

  3. Length of hospital admission [ Time Frame: During hospital admission period ]
    Number of days that patients need to stay in the hospital

  4. Furosemide dose [ Time Frame: 72 hours after randomisation ]
    Total dosage of intravenous furosemide

  5. Levels of B-type atrial natriuretic peptide (BNP) [ Time Frame: 72 hours and 7 days after randomisation ]
    levels of pro-BNP

  6. Number of participants with adverse events [ Time Frame: During hospital admission ]
    All adverse events during hospital admission

  7. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04465123


Contacts
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Contact: Kajohnsak Noppakun, MD +66815953465 kajohnsak.noppakun@cmu.ac.th
Contact: Tiranun Suriya, RN +66818812106 tingsuri@hotmail.co.th

Locations
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Thailand
Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University Recruiting
Chiang Mai, Thailand, 50200
Contact: Kajohnsak Noppakun, MD    +66815953465    kajohnsak.noppakun@cmu.ac.th   
Contact: Tiranun Suriya, RN    +66818812106    tingsuri@hotmail.co.th   
Sponsors and Collaborators
Chiang Mai University
Investigators
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Principal Investigator: Kajohnsak Noppakun, MD Instructor, Division of Nephrology, Department of Internal Medicine
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Responsible Party: Kajohnsak Noppakun, Assistant Professor of Medicine, Chiang Mai University
ClinicalTrials.gov Identifier: NCT04465123    
Other Study ID Numbers: MED-2563-07080 (2)
First Posted: July 9, 2020    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kajohnsak Noppakun, Chiang Mai University:
Acute heart failure
Diuretic resistance
Sequential nephron blockade
Diuretic combination
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Kidney Diseases
Urologic Diseases
Acute Kidney Injury
Renal Insufficiency
Hydrochlorothiazide
Spironolactone
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing