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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01752543
• Other study ID #: H-3-2012-139
• Status: Completed
• Phase: Phase 4
• First received: December 12, 2012
• Last updated: June 16, 2015
• Start date: December 2013
• Est. completion date: June 2015

Study information

• Verified date: June 2015
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research EthicsDenmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Conivaptan
Conivaptan treatment: 20 mg bolus followed by infusion of 2 mg/hour
• Placebo (Dextrose)
Placebo treatment: 20 mg bolus followed by infusion of 2 mg/hour

Locations

Country	Name	City	State
Denmark	Department of Cardiology, Copenhagen University Hospital, Rigshospital	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Finn Gustafsson	Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The joint endpoint of change in pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) at the submaximal exercise intensity of 50 % of the maximal exercise capacity		1 day	Yes
Secondary	Cardiac index (CI) during submaximal exercise from rest to submaximal exercise		1 day	Yes
Secondary	Pulmonary and systemic vascular resistance from rest to submaximal exercise		1 day	Yes
Secondary	Left ventricular end diastolic diameter during exercise from rest to submaximal exercise		1 day	No
Secondary	The change in mean pulmonary artery pressure (mPAP) from rest to submaximal exercise		1 day	Yes
Secondary	The change in BNP, MR-ANP and copeptin from rest to submaximal exercise		1 day	No