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

NCT01752543 | Completed Phase 4 DMC

• 1 other identifier: H-3-2012-139
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Keywords

Vasopressin; Exercise capacity; Conivaptan

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Cardiac index (CI) during submaximal exercise from rest to submaximal exercise

  1 day

• Pulmonary and systemic vascular resistance from rest to submaximal exercise

  1 day

• Left ventricular end diastolic diameter during exercise from rest to submaximal exercise

  1 day

• The change in mean pulmonary artery pressure (mPAP) from rest to submaximal exercise

  1 day

• The change in BNP, MR-ANP and copeptin from rest to submaximal exercise

  1 day

Study Arms (2)

Conivaptan

ACTIVE COMPARATOR

10 patients will be randomized to conivaptan treatment

Drug: Conivaptan

Dextrose

PLACEBO COMPARATOR

10 patients will receive placebo treatment (dextrose)

Drug: Placebo (Dextrose)

Interventions

Conivaptan DRUG

Conivaptan treatment: 20 mg bolus followed by infusion of 2 mg/hour

Also known as: Vaprisol

Conivaptan

Placebo (Dextrose) DRUG

Placebo treatment: 20 mg bolus followed by infusion of 2 mg/hour

Also known as: 5 % dextrose

Dextrose

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Finn Gustafsson: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Department of Cardiology, Copenhagen University Hospital, Rigshospital

Copenhagen, 2100, Denmark

Location

Related Publications (1)

• 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.

  PMID: 30057012 DERIVED

MeSH Terms

Conditions

Heart Failure; Diabetes Insipidus

Interventions

conivaptan; Glucose

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• Louise Balling, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Finn Gustafsson, MD, PhD, DMSci

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff Cardiologist, MD, Phd, DMSci

Study Record Dates

• First Submitted: December 12, 2012
• First Posted: December 19, 2012
• Study Start: December 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 17, 2015

Record last verified: 2015-06

Locations

DK (1)