Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure Patients
June 16, 2015 updated by: Finn Gustafsson
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Copenhagen, Denmark, 2100
- Department of Cardiology, Copenhagen University Hospital, Rigshospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 80 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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ACTIVE_COMPARATOR: Conivaptan
10 patients will be randomized to conivaptan treatment
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Conivaptan treatment: 20 mg bolus followed by infusion of 2 mg/hour
Other Names:
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PLACEBO_COMPARATOR: Dextrose
10 patients will receive placebo treatment (dextrose)
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Placebo treatment: 20 mg bolus followed by infusion of 2 mg/hour
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
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
Time Frame: 1 day
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1 day
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Cardiac index (CI) during submaximal exercise from rest to submaximal exercise
Time Frame: 1 day
|
1 day
|
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Pulmonary and systemic vascular resistance from rest to submaximal exercise
Time Frame: 1 day
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1 day
|
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Left ventricular end diastolic diameter during exercise from rest to submaximal exercise
Time Frame: 1 day
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1 day
|
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The change in mean pulmonary artery pressure (mPAP) from rest to submaximal exercise
Time Frame: 1 day
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1 day
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The change in BNP, MR-ANP and copeptin from rest to submaximal exercise
Time Frame: 1 day
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1 day
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Louise Balling, MD, Rigshospitalet, Denmark
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2013
Primary Completion (ACTUAL)
June 1, 2015
Study Completion (ACTUAL)
June 1, 2015
Study Registration Dates
First Submitted
December 12, 2012
First Submitted That Met QC Criteria
December 14, 2012
First Posted (ESTIMATE)
December 19, 2012
Study Record Updates
Last Update Posted (ESTIMATE)
June 17, 2015
Last Update Submitted That Met QC Criteria
June 16, 2015
Last Verified
June 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-3-2012-139
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.