Pilot Study of Using Copeptin to Predict Response to Tolvaptan

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Otsuka America Pharmaceutical
• Treatments: Tolvaptan

Criteria

Inclusion Criteria:

1. 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

2. Left ventricular ejection fraction ≤ 45% as documented by quantitative assessment by an accepted imaging technique within one year of screening

3. Meet baseline copeptin criteria for entry

4. Currently taking a diuretic (with diuretic defined as any loop or thiazide diuretic or aldosterone antagonist at any dose)

Exclusion Criteria:

1. Current New York Heart Association Functional Class IV heart failure

2. Patients who are felt to be volume depleted based on clinical examination or need to reduce diuretic administration

3. Presence of clinical contraindications to tolvaptan

4. Episode of acute myocardial infarction or acute coronary syndrome within the past 3 months

5. Cardiovascular surgical procedure within the past 4 weeks

6. CHF due to uncorrected thyroid disease, active myocarditis, or known amyloid cardiomyopathy.

7. History of primary significant liver disease or acute hepatic failure, as defined by the investigator.

8. Chronic uncontrolled diabetes mellitus as determined by the investigator.

9. Supine systolic arterial blood pressure < 90 mmHg at screening

10. Serum creatinine > 3.5 mg/dL at screening

11. Serum potassium > 5.5 mEq/L or < 3.5 mEq/L at screening

12. 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