Pilot Study of Using Copeptin to Predict Response to Tolvaptan

Study Overview
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Brief Summary
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This pilot study will investigate the association between levels of the peptide copeptin and response to tolvaptan, a drug that blocks the action of the water retaining hormone vasopressin. The study will enroll stable outpatients with CHF with reduced LVEF (≤45) selected by targeting upper and lower quartile copeptin levels at screening (10 each). The treatment phase of the study will be a prospective, single-arm, open label protocol. All patients will receive active therapy consisting of a single oral dose of 30 mg of tolvaptan with body weight, fluid intake, and urine output monitored in a research unit for 24 hours. For analysis of study endpoints, patients in the single intervention arm will be stratified by a prospectively determined cut-point of copeptin level into two groups (≥10 versus <10 pmol/L). The copeptin level used for the two group stratification will be the blinded copeptin value obtained at baseline from the hospital phase prior to administration of tolvaptan.

Detailed Description
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The study screening strategy will be designed to enroll an enriched patient population by identifying patients at the high or low end of the spectrum of copeptin levels for outpatients with stable heart failure. This will be accomplished by blinded review of copeptin levels obtained during screening. The primary endpoints for analysis will be 24 hour urine output and the change in body weight over 24 hours during the inpatient stay.

Official Title
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Pilot Study of the Relationship of Ambient Copeptin to the Aquaretic Effects of Tolvaptan in Patients With Heart Failure

Conditions
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Cardiovascular Diseases, Heart Diseases, Heart Failure

Intervention / Treatment
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* Drug: tolvaptan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients with a history of chronic symptomatic heart failure, defined as dyspnea on exertion or edema, due to cardiac dysfunction, of at least one month's duration Left ventricular ejection fraction ≤ 45% as documented by quantitative assessment by an accepted imaging technique within one year of screening Meet baseline copeptin criteria for entry Currently taking a diuretic (with diuretic defined as any loop or thiazide diuretic or aldosterone antagonist at any dose) Exclusion Criteria: Current New York Heart Association Functional Class IV heart failure Patients who are felt to be volume depleted based on clinical examination or need to reduce diuretic administration Presence of clinical contraindications to tolvaptan Episode of acute myocardial infarction or acute coronary syndrome within the past 3 months Cardiovascular surgical procedure within the past 4 weeks CHF due to uncorrected thyroid disease, active myocarditis, or known amyloid cardiomyopathy. History of primary significant liver disease or acute hepatic failure, as defined by the investigator. Chronic uncontrolled diabetes mellitus as determined by the investigator. Supine systolic arterial blood pressure < 90 mmHg at screening Serum creatinine > 3.5 mg/dL at screening Serum potassium > 5.5 mEq/L or < 3.5 mEq/L at screening Subjects currently treated with hemofiltration or dialysis j. Subjects judged by the investigator to be unable to maintain accurate intake and output during their hospitalization related to medical or other problems

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tolvaptan<br>Single arm study | Drug: tolvaptan<br>* oral, 30 mg, single dose, one time administration<br>* Other names: Samsca;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Output | Total urine output for 24 hours following tolvaptan administration | 24 hours | 
| Body Weight | Change in body weight from baseline to 24 hours after tolvaptan administration | Change over 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tolvaptan, copeptin, heart failure, vasopressin antagonist