Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management

NCT ID: NCT01584557

Last Updated: 2016-09-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2016-08-31

Brief Summary

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The purpose of this study is to evaluate the short term efficacy and safety of tolvaptan in subjects hospitalized for worsening heart failure who have volume overload and one of the following: renal insufficiency, or hyponatremia or inadequate response to diuretic therapy. The primary variable for assessing efficacy will be self-assessed 7-point dyspnea score at 8 and 16 hours.

Detailed Description

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Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Tolvaptan, Samsca

Tolvaptan, Samsca, uncoated tablet, 30 mg, once per day, up to 7 days.

Group Type ACTIVE_COMPARATOR

Tolvaptan or Samsca

Intervention Type DRUG

uncoated tablet, 30mg, once per day, for up to 7 days.

sugar pill

placebo, sugar pill

Group Type PLACEBO_COMPARATOR

placebo or sugar pill

Intervention Type DRUG

sugar pill

Interventions

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Tolvaptan or Samsca

uncoated tablet, 30mg, once per day, for up to 7 days.

Intervention Type DRUG

placebo or sugar pill

sugar pill

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Subjects hospitalized for worsening heart failure and randomized within 36 hours of initial presentation.
2. Males and females 18 years of age or older.
3. NYHA Class III or IV on admission to the hospital.
4. Able to understand content of and willing to provide written informed consent
5. Dyspnea, measured by the 5-point current dyspnea scale (moderately short of breath or worse), within 2 hours of randomization and dosing.

The following must be met within 12 hours of randomization.
6. The subject must have signs of extracellular volume expansion, defined as two or more of the following five: Signs of RHF ( jugular venous distention, pitting edema (≥1+), ascites) and/or Signs of LHF (pulmonary congestion on chest x-ray, pulmonary rales)
7. Have at least one of the following:

* eGFR \< 60ml/min/1.73m2, OR
* serum sodium ≤ 134 mEq/L, OR
* urine output ≤ 125 ml/hr over anytime frame of at least 2 hours, following administration of IV furosemide of at least 40mg. See table below.

Time Period (hr) Cumulative UO (mL) 2 \<250 3 \<375 4 \<500 5 \<625 6 \<750 7 \<875 8 \<1000

Exclusion Criteria

1. Positive urine pregnancy test for women of child bearing potential.
2. Inability to provide written informed consent.
3. Cardiac surgery within 60 days prior to study randomization.
4. Acute Coronary Syndrome (ACS) or percutaneous coronary intervention within 30 days prior to study randomization.
5. Planned revascularization procedures, cardiac mechanical support implantation, cardiac transplantation, or other cardiac surgery within 30 days following study randomization.
6. Planned electrophysiologic (EP) device implantation within 7 days following study randomization.
7. Subjects who are on cardiac mechanical support.
8. Co-morbid condition with an expected survival less than six months.
9. History of a cerebrovascular accident within the last 30 days.
10. Hemodynamically significant uncorrected primary cardiac valvular disease.
11. Hypertrophic cardiomyopathy (obstructive or non-obstructive).
12. Uncorrected thyroid disease, active myocarditis or known amyloid cardiomyopathy.
13. History of primary significant liver disease or acute hepatic failure, as defined by the investigator.
14. Chronic uncontrolled diabetes mellitus as determined by the investigator.
15. Supine systolic arterial blood pressure \< 90 mmHg.
16. Serum creatinine \> 3.5 mg/dL or undergoing dialysis.
17. Hemoglobin \< 9 g/dL
18. History of hypersensitivity and/or idiosyncratic reaction to benzazepine derivatives (such as benazepril).
19. Inability to take oral medications.
20. Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted.
21. Previous exposure to tolvaptan within 7 days prior to randomization.
22. Subjects with refractory, end-stage, heart failure defined as subjects who are appropriate candidates for specialized treatment strategies, such as ventricular assist devices, continuous positive IV inotropic therapy, or hospice care.
23. Ultrafiltration within 7 days prior to randomization or planned.
24. Active gout
25. Serum sodium \>144 mEq/L
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cardiovascular Clinical Sciences Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marvin Konstam, MD

Role: PRINCIPAL_INVESTIGATOR

Cardiovascular Clinical Sciences Inc

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

The Heart Center Research

Huntsville, Alabama, United States

Site Status

Greater Los Angeles VA Medical Center

Los Angeles, California, United States

Site Status

University of Florida Health Science Ctr. Jacksonville

Jacksonville, Florida, United States

Site Status

MIMA Century Research Associates

Melbourne, Florida, United States

Site Status

Jackson Memorial Hospital

Miami, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

University Cardiology Associates, LLC

Augusta, Georgia, United States

Site Status

Mercer University School of Medicine

Macon, Georgia, United States

Site Status

Advocate Medical Group - Oakbrook

Naperville, Illinois, United States

Site Status

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Site Status

St. Vincent Medical Group

Indianapolis, Indiana, United States

Site Status

CardioSpecialists Group

Munster, Indiana, United States

Site Status

Ochsner Medical Center

New Orleans, Louisiana, United States

Site Status

Advanced Cardiovascular Specialists

Shreveport, Louisiana, United States

Site Status

Louisiana Heart Center and Research

Slidell, Louisiana, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status

Crittenton Hospital Medical Center

Rochester, Michigan, United States

Site Status

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

Site Status

Bryan Heart Institute

Lincoln, Nebraska, United States

Site Status

The Valley Hospital

Ridgewood, New Jersey, United States

Site Status

Caromont Heart/Gaston Memorial Hospital

Gastonia, North Carolina, United States

Site Status

Duke Cardiology of Lumberton Research/Southeastern Regional Medical Cente

Lumberton, North Carolina, United States

Site Status

Akron General Medical Center

Akron, Ohio, United States

Site Status

University of Cincinnati

Cincinnatti, Ohio, United States

Site Status

Dayton Heart Center

Dayton, Ohio, United States

Site Status

The Sisters of Mercy of Hamilton, Ohio dba Mercy Hospital Fairfield

Fairfield, Ohio, United States

Site Status

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, United States

Site Status

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Memorial Hospital of RI

Pawtucket, Rhode Island, United States

Site Status

The Miriam Hosptial

Providence, Rhode Island, United States

Site Status

University of Texas Health Science Center

Houston, Texas, United States

Site Status

The Heart Hospital Baylor Plano - Research Insititute

Plano, Texas, United States

Site Status

CV Group Central Lynchburg/Stroobants Heart Center

Lynchburg, Virginia, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Konstam MA, Kiernan M, Chandler A, Dhingra R, Mody FV, Eisen H, Haught WH, Wagoner L, Gupta D, Patten R, Gordon P, Korr K, Fileccia R, Pressler SJ, Gregory D, Wedge P, Dowling D, Romeling M, Konstam JM, Massaro JM, Udelson JE; SECRET of CHF Investigators, Coordinators, and Committee Members. Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload. J Am Coll Cardiol. 2017 Mar 21;69(11):1409-1419. doi: 10.1016/j.jacc.2016.12.035.

Reference Type DERIVED
PMID: 28302292 (View on PubMed)

Other Identifiers

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CCSF-2011-001

Identifier Type: -

Identifier Source: org_study_id

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