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

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Conivaptan
Placebo (Dextrose)
Sponsored by
Finn Gustafsson
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Vasopressin, Exercise capacity, Conivaptan

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Department of Cardiology, Copenhagen University Hospital, Rigshospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Conivaptan

Dextrose

Arm Description

10 patients will be randomized to conivaptan treatment

10 patients will receive placebo treatment (dextrose)

Outcomes

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

Secondary Outcome Measures

Cardiac index (CI) during submaximal exercise from rest to submaximal exercise
Pulmonary and systemic vascular resistance from rest to submaximal exercise
Left ventricular end diastolic diameter during exercise from rest to submaximal exercise
The change in mean pulmonary artery pressure (mPAP) from rest to submaximal exercise
The change in BNP, MR-ANP and copeptin from rest to submaximal exercise

Full Information

First Posted
December 12, 2012
Last Updated
June 16, 2015
Sponsor
Finn Gustafsson
Collaborators
Rigshospitalet, Denmark
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1. Study Identification

Unique Protocol Identification Number
NCT01752543
Brief Title
Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure Patients
Official Title
Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure Patients
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Finn Gustafsson
Collaborators
Rigshospitalet, Denmark

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Vasopressin, Exercise capacity, Conivaptan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Conivaptan
Arm Type
Active Comparator
Arm Description
10 patients will be randomized to conivaptan treatment
Arm Title
Dextrose
Arm Type
Placebo Comparator
Arm Description
10 patients will receive placebo treatment (dextrose)
Intervention Type
Drug
Intervention Name(s)
Conivaptan
Other Intervention Name(s)
Vaprisol
Intervention Description
Conivaptan treatment: 20 mg bolus followed by infusion of 2 mg/hour
Intervention Type
Drug
Intervention Name(s)
Placebo (Dextrose)
Other Intervention Name(s)
5 % dextrose
Intervention Description
Placebo treatment: 20 mg bolus followed by infusion of 2 mg/hour
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Cardiac index (CI) during submaximal exercise from rest to submaximal exercise
Time Frame
1 day
Title
Pulmonary and systemic vascular resistance from rest to submaximal exercise
Time Frame
1 day
Title
Left ventricular end diastolic diameter during exercise from rest to submaximal exercise
Time Frame
1 day
Title
The change in mean pulmonary artery pressure (mPAP) from rest to submaximal exercise
Time Frame
1 day
Title
The change in BNP, MR-ANP and copeptin from rest to submaximal exercise
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Louise Balling, MD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Finn Gustafsson, MD, PhD, DMSci
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiology, Copenhagen University Hospital, Rigshospital
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
30057012
Citation
Balling L, Thomsen JH, Wolsk E, Hassager C, Boesgaard S, Goldsmith SR, Gustafsson F. Hemodynamic effects of short-term infusion of a vasopressin V1A/V2 receptor antagonist conivaptan in patients withchronic heart failure during submaximal exercise. Am Heart J. 2018 Sep;203:101-104. doi: 10.1016/j.ahj.2018.05.015. Epub 2018 Jun 14. No abstract available.
Results Reference
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Effects on Exercise Hemodynamics of Vasopressin Blockade by Conivaptan Infusion in Heart Failure Patients

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