Tolvaptan add-on Therapy to Overcome Loop Diuretic Resistance in Acute Heart Failure With Renal Dysfunction (DR-AHF)

August 9, 2022 updated by: Gia Dinh People Hospital
Renal dysfunction, which comprises 10%-40% of acute heart failure patients (AHF), plays an important role in diuretic resistance mechanism. DR-AHF was designed to demonstrate the effectiveness of early tolvaptan (a vasopressin-2 receptor antagonist) add-on therapy in acute heart failure patients with renal dysfunction and clinical evidence of loop diuretic resistance.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single-center, open-label, randomized controlled trial, which will enroll 128 patients hospitalized due to AHF. These patients with wet-warm phenotype whose estimated glomerular filtration rates at admission are above 15 and below 60 mL/min/1.73 m2, and cumulative urine output <300 mL in 2 hours after the first dose of intravenous furosemide will be randomly assigned 1:1 to receive a standard care with uptitrating intravenous furosemide alone or a combination therapy with tolvaptan 15mg once daily for 2 days. The standard furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association. The primary endpoint is the cumulative urine output at 48 hour. Key secondary endpoints include the improvement of fractional excretion of sodium at 6 hour, the total dose of furosemide, the changes in the body weights, the net fluid loss, the lessening of diastolic dysfunction parameters on echocardiography, and the incidence of clinically relevant worsening renal function at 48 hour.

Study Type

Interventional

Enrollment (Anticipated)

128

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Vietnam
      • Ho Chi Minh City, Vietnam, 70000
        • Recruiting
        • Cardiology Department
        • Contact:
        • Contact:
        • Principal Investigator:
          • Anh H Nguyen, M.D
        • Principal Investigator:
          • Thao T Nguyen, M.D
        • Principal Investigator:
          • Tin T Huynh, M.D
        • Sub-Investigator:
          • Hoa K Tran, M.D
        • Sub-Investigator:
          • Matsue Yuya, Ph.D

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

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Admitted to hospital with a primary diagnosis of acute heart failure with wet-warm phenotype
  • Cumulative urine volume output < 300ml within 2 hours after the first dose of intravenous furosemide
  • eGFR at admission 15-60ml/min/1.73m2

Exclusion Criteria:

  • Acute coronary syndrome
  • Anuria
  • Sepsis
  • Consciousness impairment
  • Pregnant or breastfeeding women
  • Severe valvular heart diseases (severe valvular stenosis or regurgitation)
  • Admission sodium level > 140 mEq/L
  • Serum total bilirubin > 3 mg/dL
  • Serum potassium > 5.5 mmol/L
  • Allergy or contraindication for tolvaptan
  • Emergency indication for hemodialysis
  • Cardiogenic shock or mechanical circulation support

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Conventional diuretic group
The conventional furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association
Drug: Tolvaptan 15 MG
vasopressin-2 receptor antagonist 15mg once daily is added-on to the conventional diuretic strategy
Other Names:
  • Samsca
Active Comparator: Vasopressin-2 antagonist group
Tolvaptan 15mg once daily for 2 days will be added-on the furosemide strategy based on the modified 2019 Position Statement from the ESC Heart Failure Association
Drug: Tolvaptan 15 MG
vasopressin-2 receptor antagonist 15mg once daily is added-on to the conventional diuretic strategy
Other Names:
  • Samsca

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative urine volume output at 48h after randomization
Time Frame: Hour 48
Urine volume in mL
Hour 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative dose of furosemide at 48h after randomization
Time Frame: Hour 48
Furosemide dose in mg
Hour 48
Symptom of dyspnea by 7-point Likert scale at 24h and 48h after randomization
Time Frame: Hour 24, Hour 48
3: markedly better, 2: moderately better, 1: minimally better, 0: no change, -1: minimally worse, -2: moderately worse, -3: markedly worse
Hour 24, Hour 48
Changes in body weight at 24h and 48h after randomization
Time Frame: Hour 24, Hour 48
weight in gram
Hour 24, Hour 48
Incidence of clinically relevant worsening renal function at 24h and 48h after randomization
Time Frame: Hour 24, Hour 48
An increase in serum creatinine ≥ 0.3 mg/dL within 48 hours accompanying doubling the dose of furosemide according to the diuretic treatment protocol
Hour 24, Hour 48
Changes in serum electrolytes measured at 12h, 24h and 48h after randomization
Time Frame: Hour 12, Hour 24, Hour 48
Changes in serum sodium (mmol/L), potassium (mmol/L), chloride (mmol/L)
Hour 12, Hour 24, Hour 48
Changes in urine electrolyte excretion at 6h, 24h and 48h
Time Frame: Hour 6, Hour 24, Hour 48
Increase in sodium (mmol/L), potassium (mmol/L) and chloride (mmol/L) excretion adjusted for urine creatinine (umol/L)
Hour 6, Hour 24, Hour 48
Changes in NT-proBNP at 48h after randomization
Time Frame: Hour 0, Hour 48
Changes in NT-proBNP (pg/mL)
Hour 0, Hour 48
Changes in mitral e' on echocardiography
Time Frame: Hour 24, Hour 48
Average of septal e' (cm/s) and lateral e' (cm/s) on tissue doppler imaging in apical 4-chamber view
Hour 24, Hour 48
Changes in E/e' ratio on echocardiography
Time Frame: Hour 24, Hour 48
The ratio between mitral E (cm/s) and average e' (cm/s)
Hour 24, Hour 48
Changes in left atrial volume on echocardiography
Time Frame: Hour 24, Hour 48
Average of left atrial volumes (ml) by Simpson's rule in apical 4-chamber and 2-chamber view
Hour 24, Hour 48
Changes in tricuspid regurgitation maximal velocity on echocardiography
Time Frame: Hour 24, Hour 48
Tricuspid regurgitation maximal velocity (m/s) by continuous wave doppler in apical 4-chamber view
Hour 24, Hour 48
Changes in inferior vena cava maximal diameter on echocardiography
Time Frame: Hour 24, Hour 48
Inferior vena cava maximal diameter (mm) in subcostal view
Hour 24, Hour 48

Collaborators and Investigators

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

Sponsor

Gia Dinh People Hospital

Collaborators

Otsuka Pharmaceutical Vietnam

Investigators

  • Study Chair: Hai H. Nguyen, Ph.D, Cardiology Department

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

December 1, 2021

Primary Completion (Anticipated)

June 30, 2023

Study Completion (Anticipated)

July 26, 2023

Study Registration Dates

First Submitted

March 27, 2020

First Submitted That Met QC Criteria

April 1, 2020

First Posted (Actual)

April 2, 2020

Study Record Updates

Last Update Posted (Actual)

August 11, 2022

Last Update Submitted That Met QC Criteria

August 9, 2022

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 92/CN-HĐĐĐ

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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