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

NCT04331132 | Unknown DMC

• 1 other identifier: 92/CN-HĐĐĐ
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Heart Failure

Keywords

acute heart failure; worsening renal function; loop diuretic resistance; vasopressin-2 receptor antagonist

Outcome Measures

Primary Outcomes (1)

• Cumulative urine volume output at 48h after randomization

  Urine volume in mL

  Hour 48

Secondary Outcomes (12)

• Cumulative dose of furosemide at 48h after randomization

  Hour 48

• Symptom of dyspnea by 7-point Likert scale at 24h and 48h after randomization

  Hour 24, Hour 48

• Changes in body weight at 24h and 48h after randomization

  Hour 24, Hour 48

• Incidence of clinically relevant worsening renal function at 24h and 48h after randomization

  Hour 24, Hour 48

• Changes in serum electrolytes measured at 12h, 24h and 48h after randomization

  Hour 12, Hour 24, Hour 48

Study Arms (2)

Conventional diuretic group

PLACEBO COMPARATOR

The conventional furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association

Drug: Tolvaptan 15 MG

Vasopressin-2 antagonist group

ACTIVE COMPARATOR

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

Interventions

Tolvaptan 15 MG DRUG

vasopressin-2 receptor antagonist 15mg once daily is added-on to the conventional diuretic strategy

Also known as: Samsca

Conventional diuretic group; Vasopressin-2 antagonist group

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gia Dinh People Hospital: lead
• Otsuka Pharmaceutical Vietnam: collaborator

Study Sites (1)

Cardiology Department

Ho Chi Minh City, 70000, Vietnam

RECRUITING

Related Publications (4)

• Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available.

  PMID: 27206819 BACKGROUND

• Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Mar 17;75(10):1178-1195. doi: 10.1016/j.jacc.2019.12.059.

  PMID: 32164892 BACKGROUND

• Mullens W, Damman K, Harjola VP, Mebazaa A, Brunner-La Rocca HP, Martens P, Testani JM, Tang WHW, Orso F, Rossignol P, Metra M, Filippatos G, Seferovic PM, Ruschitzka F, Coats AJ. The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019 Feb;21(2):137-155. doi: 10.1002/ejhf.1369. Epub 2019 Jan 1.

  PMID: 30600580 BACKGROUND

• Minh NG, Hoang HN, Maeda D, Matsue Y. Tolvaptan Add-on Therapy to Overcome Loop Diuretic Resistance in Acute Heart Failure With Renal Dysfunction (DR-AHF): Design and Rationale. Front Cardiovasc Med. 2022 Jan 27;8:783181. doi: 10.3389/fcvm.2021.783181. eCollection 2021.

  PMID: 35155599 DERIVED

MeSH Terms

Interventions

Tolvaptan

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Hai H. Nguyen, Ph.D

  Cardiology Department

  STUDY CHAIR

Central Study Contacts

Nhat M. Giang, M.D

CONTACT

+84919963999; minhnhat_210189@yahoo.com

Hai H. Nguyen, Ph.D

CONTACT

+84908247359; bsnguyenhoanghai@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Acute heart failure 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

Study Record Dates

• First Submitted: March 27, 2020
• First Posted: April 2, 2020
• Study Start: December 1, 2021
• Primary Completion: June 30, 2023
• Study Completion: July 26, 2023
• Last Updated: August 11, 2022

Record last verified: 2021-09

Locations

VN (1)