Pilot Study of Using Copeptin to Predict Response to Tolvaptan

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Intervention / Treatment: Drug: tolvaptan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Tolvaptan; Single arm study	Drug: tolvaptan; oral, 30 mg, single dose, one time administration; Other Names: Samsca

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Otsuka America Pharmaceutical
• Investigators: Principal Investigator: Kirkwood F Adams, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: April 29, 2011
• First Submitted That Met QC Criteria: April 29, 2011
• First Posted (Estimate): May 2, 2011

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: April 11, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: heart failure; copeptin; tolvaptan; vasopressin antagonist
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Pituitary Diseases; Heart Failure; Heart Diseases; Cardiovascular Diseases; Diabetes Insipidus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: TOLCOPEP11