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

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 20

Inclusion Criteria

-Age > 18 years
-LVEF < 45 %
-Treatment with beta-blockers and ACE-inhibitors for at least 1 month
-NYHA-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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

-Signs of symptomatic or ongoing myocardial ischemia
-Presence of hypovolemic hyponatremia (as judged by the investigator)
-Clinical signs of volume depletion or dehydration
-Hypernatremia (P-Na+) > 145 mmol/L
-Chronic obstructive pulmonary disease (FEV1 < 1L)
-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
-Uncontrolled cardiac arrhythmias
-Untreated serious hypothyroidism
-Adrenal insufficiency
-Poor echocardiographic window
-Not able 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
-Severely decreased kidney function (eGFR < 20 ml/min)
-Serum K+< 3.5 or > 5.5 mmol/L
-Conivaptan intolerability
-Corn allergy
-Treatment with potent CYP3A-inhibitors (ketoconazole, otrakonazole, clarithromycin, ritonavir, indinavir)
-Treatment with arginine vasopressin, oxytocin, desmopressin and other medications for the treatment of hyponatremia (lithium salts, urea and demeocycline)
-Warfarin treatment
-Presence of infection or active bleeding
-Need of inotropic circulatory support within the last 30 days
-Pregnant women or fertile women not taking safe contraception
-Women who are breastfeeding
-Hemodynamically significant heart valve disease estimated by echocardiography
-The ability to understand written and oral Danish
-Contraindication to insertion of Swan-Ganz catheter

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To test if infusion of the V1A/V2-receptor blocker conivaptan improves hemodynamics and physical capacity in HF patients on optimal HF medical therapy and to improve understanding of the role of vasopressin in HF.;Secondary Objective: Not applicable;Primary end point(s): -PCWP at the submaximal exercise intensity of 50 % of the maximal exercise capacity ;Timepoint(s) of evaluation of this end point: 1 day

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Cardiac index (CI) during submaximal exercise before and during conivaptan-infusion<br>-Pulmonary and peripheral vascular resistance during exercise<br>-Left ventricular end diastolic diameter during exercise<br>-The Doppler-index of the left ventricular filling (E/e’) during exercise<br>-The change in BNP, MR-ANP and copeptin from rest to submaximal exercise<br>;Timepoint(s) of evaluation of this end point: 1 day