Acute Heart Failure Patients With High Copeptin Treated With Tolvaptan Targets Increased AVP Activation for Treatment (ACTIVATE)

Study Overview
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Brief Summary
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Patients being hospitalized for acute heart failure and already receiving standard therapy will be randomized to receive either tolvaptan or placebo, based on the level of copeptin measured in their bloodstream. Patients with high copeptin levels will be able to participate in the trial, patients with low levels will be excluded. Patients being admitted to the observation unit for acute heart failure and already receiving standard therapy will be randomized to receive either tolvaptan or placebo without consideration of the copeptin level. The hypothesis is that patients receiving tolvaptan will have better improvement of shortness of breath than those receiving placebo, within 9 hours of drug administration.

Official Title
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Acute Heart Failure With High Copeptin Levels Treated With Tolvaptan Targets Increased AVP Activation for Treatment Efficacy

Conditions
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Acute Heart Failure

Intervention / Treatment
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* Drug: Tolvaptan
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Older than or equal to 18 years of age, with diagnosis and planned treatment for Acute Heart Failure Dyspnea at rest or minimal exertion per the patient Evidence of extracellular volume expansion by at least one of the following: JVD, Rales, Ascites, Edema or positive Chest X-ray defined as cardiomegaly, pulmonary vascular congestion, Kerley B-lines, pulmonary edema and/or pleural effusion. Elevated BNP level >200 pg/ml, or NTproBNP > 1000pg/mL Able to administer study drug within 8 hours from triage time Inpatient Hospitalized Inclusion Only: Co-peptin level > 27 pmol/L Exclusion Criteria: Unable to provide informed consent Unable to have 30 day telephone follow up Not expected to survive past 6 months On Renal replacement therapy or creatinine >3.5 History of allergy or intolerance to Tolvaptan Suspected Pregnancy Cardiogenic Shock Participation in any interventional trial in prior 30 days. Receiving or planned to receive IV Inotropic therapy ACS now or in the past 30 days Treatment with IV infusion vasoactive drugs in the hour prior to enrollment Temperature > 100.5 Heart Failure due to atrial fibrillation with Rapid Ventricular Response SBP < 90 mmHg

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard therapy plus Tolvaptan<br>Patient in the interventional group will receive tolvaptan in addition to standard therapy | Drug: Tolvaptan<br>* Tolvaptan 30 mg. tablet for subjects enrolled prior to first 8 hours of coming to an emergency department. Repeated daily up to 5th day.<br>* Other names: Samsca;|
| Placebo Comparator: Standard therapy plus placebo<br> | Drug: placebo<br>* Patient in the placebo group will receive tolvaptan in addition to standard therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea | Dyspnea will be evaluated at 9 hours | 9 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay | The length of hospitalization will be compared between the placebo and interventional cohorts | during hospitalizaton | 
| Rehospitalization | The number and length of re-hospitalizations will be compared between the placebo and interventional cohorts | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute heart failure, emergency department, copeptin, adh antagonists