Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure Patients

Finn Gustafsson

Status and phase

Completed

Phase 4

Conditions

Heart Failure

Treatments

Drug: Placebo (Dextrose)

Drug: Conivaptan

Study type

Interventional

Funder types

Other

Identifiers

NCT01752543

H-3-2012-139

Details and patient eligibility

About

The purpose of the present study is to evaluate the effects of a blockade of the vasopressin system and central hemodynamic system in heart failure (HF) patients during physical exercise. The significance of the vasopressin system during physical exercise is unclear. If vasopressin is a significant regulator of exercise hemodynamics in HF, strategies to intervene against activation of the V1A-receptor might be expected to improve HF symptoms and possibly outcome.

The potential effects of the central hemodynamic system will be evaluated with a Swan-Ganz catheter. Echocardiography will be performed at rest and during submaximal working capacity before and during the infusion of a vasopressin receptor antagonist (conivaptan) or placebo. Cardiac output will be measured by thermodilution. The exercise test will be performed at 50 % of VO2 max and hemodynamic and echocardiographic measurements will be collected. The exercise test will be performed on a supine multistage bicycle.

Enrollment

20 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age > 18 years
Left ventricular ejection fraction (LVEF) < 45 % on the baseline echocardiography.
Treatment with beta-blockers and angiotensin-converting-enzyme (ACE) inhibitors for at least 1 month as tolerated
New York Heart Association (NYHA) Functional Class II-III
Given informed consent
Women, who have not yet entered menopause (defined as no menstrual bleeding in the last 12 months), will provide a negative urine HCG before entering the study

Exclusion criteria

Signs of symptomatic or ongoing myocardial ischemia
Known non-revascularized coronary disease
Presence of hypovolemic hyponatremia (P-Na+ <130 mmol/l and clinical signs of volume depletion or dehydration as judged by investigator).
Hypernatraemia (P-Na+) > 145 mmol/L
Chronic obstructive pulmonary disease (FEV1/FVC < 70 % and/or 30 % > FEV1 < 50 %)
Supine systolic blood pressure < 85 mmHg
Significant orthostatic hypotension
Standing blood pressure < 80 mmHg or a blood pressure drop > 20 mmHg when changing from a supine to a standing position
Uncontrolled hypertension evaluated by the investigator
Uncontrolled cardiac arrhythmias evaluated by the investigator
Untreated serious hypothyroidism
Adrenal insufficiency
Poor echocardiographic window
Inability to perform exercise testing
Permanent atrial fibrillation or atrial fluttering
Planned coronary by-pass surgery
Moderate hepatic impairment (ALAT/ASAT > 3 UNL)
Presence of other diseases affecting treatment with conivaptan or the evaluation of safety as evaluated by the investigator
Severely decreased kidney function (eGFR < 20 mL/min)
Serum K+< 3.5 or > 5.5 mmol/L
Known conivaptan intolerability
Corn allergy
Dextrose Allergy
Treatment with potent CYP3A-inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir)
Treatment with arginine vasopressin, oxytocin, desmopressin and other medications for the treatment of hyponatremia (lithium salts, urea and demeclocycline)
Warfarin treatment
Presence of infection or active bleeding