Text Size

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

This study is not yet open for participant recruitment.
Verified December 2012 by Rigshospitalet, Denmark
Sponsor:
Collaborator:
Rigshospitalet, Denmark
Information provided by (Responsible Party):
Finn Gustafsson, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01752543
First received: December 12, 2012
Last updated: December 14, 2012
Last verified: December 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Heart Failure
 Drug: Conivaptan
Drug: Placebo (Dextrose)
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Cardiac index (CI) during submaximal exercise from rest to submaximal exercise [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Pulmonary and systemic vascular resistance from rest to submaximal exercise [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Left ventricular end diastolic diameter during exercise from rest to submaximal exercise [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • The change in mean pulmonary artery pressure (mPAP) from rest to submaximal exercise [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • The change in BNP, MR-ANP and copeptin from rest to submaximal exercise [ Time Frame: 1 day ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: February 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Conivaptan
10 patients will be randomized to conivaptan treatment
 Drug: Conivaptan
Conivaptan treatment: 20 mg bolus followed by infusion of 2 mg/hour
Other Name: Vaprisol
Placebo Comparator: Dextrose
10 patients will receive placebo treatment (dextrose)
 Drug: Placebo (Dextrose)
Other Name: 5 % dextrose

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01752543

Contacts
Contact: Finn Gustafsson, MD, PhD, DMSci 004535459743 finn.gustafsson@regionh.dk
Contact: Louise Balling, MD 004523451679 louise.balling@dadlnet.dk

Locations
Denmark
Department of Cardiology, Copenhagen University Hospital, Rigshospital Not yet recruiting
Copenhagen, Denmark, 2100
Contact: Finn Gustafsson, MD, PhD, DMSci     004535459743     finn.gustafsson@regionh.dk    
Contact: Louise Balling, MD     004523451679     louise.balling@dadlnet.dk    
Sponsors and Collaborators
Finn Gustafsson
Rigshospitalet, Denmark
Investigators
Principal Investigator: Louise Balling, MD Rigshospitalet, Denmark
Principal Investigator: Finn Gustafsson, MD, PhD, DMSci Rigshospitalet, Denmark
  More Information

No publications provided

Responsible Party: Finn Gustafsson, Staff Cardiologist, MD, Phd, DMSci, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01752543     History of Changes
Other Study ID Numbers: H-3-2012-139
Study First Received: December 12, 2012
Last Updated: December 14, 2012
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Medicines Agency

Keywords provided by Rigshospitalet, Denmark:
Vasopressin
Exercise capacity
Conivaptan

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Vasopressins
Arginine Vasopressin
Hemostatics
Coagulants
Hematologic Agents
 Therapeutic Uses
Pharmacologic Actions
Vasoconstrictor Agents
Cardiovascular Agents
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 18, 2013