Tolvaptan For Worsening Outpatient Heart Failure: Role of Copeptin In Identifying Responders

• Status: Completed
• Trial end date: 2021-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Patients who present to clinic or in the outpatient setting with worsening heart failure represent a unique opportunity for novel approaches to decongestion (removing fluid) that may more rapidly improve fluid status and symptoms as well as reduce the risk of hospitalization.

In these patients with less severe congestion (fluid overload), combining the vasopressin antagonist tolvaptan with loop diuretics (or fluid pills like furosemide/bumetanide/torsemide) may represent a more effective strategy for decongestion. In addition, looking at patients' copeptin levels may help identify those who are more likely to respond to tolvaptan.

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

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Otsuka America Pharmaceutical
• Treatments: Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Tolvaptan

Criteria

Inclusion Criteria:

• ≥ 18 years of age

• Presenting to clinic with worsening heart failure due congestion (fluid overload) Patient reported worsening fluid overload based on perception of edema and/or weight gain With at least one of the following symptoms

• Worsening dyspnea on exertion or fatigue

• Worsening orthopnea or paroxysmal nocturnal dyspnea (PND)

• Perception of abdominal and/or lower extremity edema

• Early satiety and/or decreased appetite And at least one of the following signs

• Lower extremity edema

• Ascites

• Elevated jugular venous distension (JVD)

• Pulmonary rales

• Daily oral dose of loop diuretic

• Prior history of heart failure with this diagnosis for at least 1 month with preserved or reduced left ventricular ejection fraction

• Signed informed consent

Exclusion Criteria:

• Patients with symptomatic hyponatremia will be excluded from the study.

• Patients with severe hyponatremia, defined as serum sodium < 125 milliequivalents per Liter (mEq/L) at the time of screening, will be excluded regardless of whether they are symptomatic or not.

• Patients with the following predisposing factors for osmotic demyelinating syndrome (ODS), assessed by the study investigator judgment, will be excluded: chronic alcoholism at the time of study, severe liver disease, marked malnutrition, and risk for chronic hypoxia.

• Patients currently undergoing renal replacement therapy

• Planned hospitalization for acute heart failure

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

• Hemodynamically significant arrhythmias

• Acute coronary syndrome (ACS) or acute myocardial infarction within 4 weeks prior to study entry

• Active myocarditis

• Hypertrophic obstructive, restrictive, or constrictive cardiomyopathy

• Severe stenotic valvular disease amendable to surgical treatment

• Complex congenital heart disease

• Constrictive pericarditis

• Clinical evidence of digoxin toxicity

• History of adverse reaction or clinical contraindication to tolvaptan

• Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors

• Inability of patient to sense and/or respond to thirst

• History of hypersensitivity to tolvaptan

• Patient is anuric

• Enrollment or planned enrollment in another randomized clinical trial during the study period

• Pregnant or breast-feeding

• Inability to comply with planned study procedures