Phase 4 N=40 Randomized Triple-blind Treatment

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

Congestive Heart Failure

Bottom Line

View on ClinicalTrials.gov: NCT02476409 ↗

Enrolled (actual)

Serious AEs

25.0%

Results posted

May 2022

Primary outcome: Primary: Change in Body Weight at 48 Hours — -3.3; -0.8 pounds — p=0.094

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: tolvaptan (Drug); Placebo (Other)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University of North Carolina, Chapel Hill
Primary completion: May 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Body Weight at 48 Hours	-3.3; -0.8	0.094
PRIMARY Change in Body Weight at 48 Hours Stratified by Copeptin	-2.9; 0.3; -3.8; -2.4	0.166
SECONDARY Changes in Visual Analog Scale - Patient Dyspnea	21; 15	0.543
SECONDARY Change in Loop Diuretic Dose (Furosemide Milligram Equivalents) at 48 Hours	-57; -11	0.050
SECONDARY Number of Participants With a Decrease in Loop Diuretic Dosing at 48 Hours	9; 4	0.092
SECONDARY Change in Loop Diuretic Score Defined Based on Change in Loop Diuretic Use	-0.47; 0	0.034 sig
SECONDARY Change in Body Weight at Day 8	-1.8; -2.8	0.643

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.

Eligibility 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02476409). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.