Aquaresis Utility for Hyponatremic Acute Heart Failure Study

NCT ID: NCT02183792

Last Updated: 2019-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2018-03-31

Brief Summary

Hyponatremia is a common finding in acute heart failure (HF) patients and is associated with worse prognosis. In addition to its prognostic value, hyponatremia may have importance during the acute management of HF. We've recently shown that acute or chronic hyponatremia, especially <130 mEq/L, was associated with higher loop diuretic dose requirements and more frequent need for escalation of the diuretic regimen to achieve the same level of diuresis as normonatremic HF patients. Aquaresis with tolvaptan represents a potentially advantageous approach to the management of volume overload in HF, especially in patients presenting with concomitant hyponatremia. The purpose of the current study is to prospectively evaluate the comparative efficacy and safety of a tolvaptan-based diuretic regimen compared to conventional diuresis with a furosemide-based regimen on short-term clinical and treatment outcomes in hyponatremic acute HF patients.

This will be a prospective, open-label, parallel-group, randomized study comparing a tolvaptan-based aquaretic regimen to a conventional continuous infusion loop diuretic-based regimen of furosemide. Up to 55 (target sample size of 50) adult subjects admitted with acute HF and signs of volume overload, and serum sodium less than 135 mEq/L will be randomized to tolvaptan or furosemide treatment arms. The initial 24 hours of study treatment will compare tolvaptan monotherapy to furosemide monotherapy. After the initial 24 hours, treatment regimens may be altered to achieve desired clinical goals. Patients will be followed for up to 96 hours and at discharge for study purposes.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tolvaptan

Tolvaptan 30-60mg once daily (with rescue loop diuretic or metolazone)

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

Furosemide

Furosemide continuous infusion 5mg/h with option to titrate (with rescue metolazone)

Group Type: ACTIVE_COMPARATOR

Furosemide

Intervention Type: DRUG

Interventions

Tolvaptan

Intervention Type: DRUG

Furosemide

Intervention Type: DRUG

Other Intervention Names

Samsca; Lasix

Eligibility Criteria

Inclusion Criteria

• Acute HF with signs or symptoms of volume overload [i.e. elevated jugular venous pulsation (JVP), rales, edema]
• Serum sodium < 135 mEq/L at time of or within first 48 hours of hospitalization
• Randomized within 48 hours of presentation to hospital
• ≥ 18 years of age
• Informed consent

Exclusion Criteria

• Severe symptomatic hyponatremia requiring acute treatment
• Severe renal impairment upon admission (creatinine clearance < 20 mL/min)
• Renal replacement therapy dependent, or requiring upon admission
• Acute coronary syndrome on admission
• Requires or has a mechanical circulatory support device
• Evidence of cardiogenic shock requiring intravenous vasopressors
• Pregnancy
• Patient requiring concomitant use of strong CYP3A4 inhibitors (clarithromycin, ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, and telithromycin)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka America Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Tien Ng

Associate Professor of Clinical Pharmacy and Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tien Ng, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Uri Elkayam, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

Keck Medical Center of USC

Los Angeles, California, United States

LAC+USC Medical Center

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HS-13-00705

Identifier Type: -

Identifier Source: org_study_id