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VAMP: Early Use of Vasopressin in Post-Fontan Management

Sponsor
Medical College of Wisconsin (Other)
Overall Status
Completed
CT.gov ID
NCT03088345
Collaborator
(none)
20
Enrollment
1
Location
2
Arms
22.8
Actual Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an investigator initiated, prospective, single-center, double-blinded, randomized, placebo-controlled trial of post-operative low dose vasopressin infusions as an early treatment of low systemic perfusion in pediatric patients following Fontan palliation.

Condition or Disease Intervention/Treatment Phase
  • Drug: Vasopressin, Arginine
  • Drug: Placebo
 Phase 2/Phase 3

Detailed Description

The treatments for preventing and managing low cardiac output syndrome after congenital heart surgery with cardiopulmonary bypass include manipulations of vascular volume and infusions of phosphodiesterase inhibitors (milrinone) and catecholamines (epinephrine and norepinephrine) for inotropic and vasoactive effects, all of which have associated risks which can contribute to morbidity and mortality. Vasopressin, a vasoactive drug with efficacy in septic shock, has also been utilized to improve postoperative hemodynamics after cardiac surgery in children. It is a common institutional practice to use vasopressin in this patient population, but usually after escalation through two or three other vasoactive drugs. There have been several studies in pediatrics and adults which suggest that vasopressin is not inferior to other vasoconstrictor therapies, and advantageous when looking at specific end points. The investigators propose to randomize the use of vasopressin to use at an earlier point in our typical post-operative medication strategy. The proposed study is a double blinded, randomized, placebo control study of vasopressin infusion immediately after the completion Fontan operation. The goal is to identify a vasoactive treatment strategy that improves hemodynamics with lower catecholamine infusion burden, reduces volume of fluid resuscitation, and reduces in-hospital resource utilization.

Neonatal and pediatric interventions associated with congenital heart disease (CHD) continue to produce improved outcomes. There are no established guidelines for managing patients after congenital heart surgery due to lesion-specific unique challenges in the post-operative period. Volume resuscitation and catecholamine infusions are the traditional treatment methods to maintain adequate perfusion. However, these two treatment modalities are associated with increased risk of worsening lung function and prolonged ventilator support with aggressive fluid resuscitation, increased myocardial oxygen demand, and precipitation of arrhythmias. Given the multifactorial etiology of postoperative low cardiac output syndrome, it is often unclear which catecholamine infusion is optimal to improve circulatory function. Vasopressin, an alternative vasoactive therapy commonly utilized in shock, has been utilized to improve postoperative hemodynamics in neonatal and pediatric patient populations and has recently gained more attention.

The use of arginine vasopressin infusion in infants and children after cardiac surgery was first reported in 1999 in a case series of 11 patients with vasodilatory shock in the postoperative period. This case series reported initiation of vasopressin for hypotension refractory to traditional treatment methods and reported a significant rise in hemodynamics with improved blood pressure in all patients as well as weaning inotropic support in 10/11 patients. Since this study there have been conflicting reports regarding vasopressin levels and the use of vasopressin to improve hemodynamics. Results from a study published in 2008 evaluated vasopressin levels in 39 patients with CHD in the pre and post-operative periods and concluded that children do not have deficient levels of vasopressin following surgery with cardiopulmonary bypass (CPB). In addition, lower levels were not associated with hypotension. A larger study in 2010 of 121 patients who had congenital heart surgery with CPB described results suggestive of clinically important hypotension associated with low vasopressin levels. Several other publications have reported improved blood pressure and decreased catecholamine usage in patients with CHD. Two of these reports have focused on vasopressin use in infants with single ventricle physiology. In all of these reported case series the vasopressin infusion has been initiated in the post-operative period as a rescue therapy. None of the studies have advocated for initiation of vasopressin immediately post-operatively and prior to a time period of hemodynamic instability, except for one retrospective chart review by Alten et al. This study from 2012 initiated vasopressin in the operating room after CPB in 19 neonates undergoing either an arterial switch for d-transposition of the great arteries or the Norwood palliation procedure for hypoplastic left heart syndrome. In this study, all neonates in whom vasopressin was initiated in the operating room received significantly lower amounts of volume replacement and catecholamine support in the immediate post-operative period. They also described lower heart rate, lower incidence of arrhythmias, shorter duration of mechanical ventilation and shorter intensive care unit stay when compared to lesion-matched control group. More recently in 2016, a single center retrospectively reviewed their experience with vasopressin and patients undergoing Fontan operations over a 10 year period and it's effects on chest tube output. They determined that patients receiving vasopressin perioperatively had less chest tube output and shorter duration of chest tube drainage in addition to shorter hospital length of stay and improved fluid balance as compared to historical controls.

There is a gap in the literature describing improved outcomes with a specific targeted vasoactive and inotropic therapy regimen to use in the post-operative Fontan procedure patients. This proposed novel study will further provide evidence for outcome based post-operative medical interventions. The proposed study is a double blinded, randomized control study of vasopressin infusion versus placebo in the first 24-hours after Fontan completion. The aim of this study is to evaluate the impact of vasopressin on the early postoperative course in a relatively homogenous population, with specific attention to catecholamine use, hemodynamics, pleural drainage, extracardiac organ function (kidney and liver) and length of stay. Furthermore, the investigators plan to evaluate vasopressin levels between the two groups.

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Use of Arginine Vasopressin in Early Postoperative Management After Fontan Palliation
Actual Study Start Date :
Mar 6, 2017
Actual Primary Completion Date :
Nov 1, 2018
Actual Study Completion Date :
Jan 28, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Vasopressin, Arginine

Patients randomized to this arm will receive a continuous arginine vasopressin in normal saline carrier infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery.

Drug: Vasopressin, Arginine
Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
Other Names:
  • Arginine Vasopressin

    		•
    Placebo Comparator: Placebo

    Patients randomized to this arm will receive a continuous normal saline carrier infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery.

    Drug: Placebo
    Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    Other Names:
  • Normal Saline

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Hemodynamics as Characterized by Vasoactive Inotrope Score (VIS) [48 hours post-operative]

      The vasoactive inotrope score (VIS) is a linear sum of vasoactive and inotrope durg infusion doses. It is usually reported as dimensionless but is sometimes reported as normalized to dopamine mcg/kg/min equivalents. The score starts at 0 and has no defined upper limit, with a commonly observed range 0-50. It is used as a measure of the intensity of hemodynamic support, with higher scores indicating more vasoactive drug support for patients. The relationship of VIS to other patient outcomes is not consistent. It will be calculated hourly for all subjects and compared between groups over the entire observation timeframe.

    2. Hemodynamics as Characterized by Mean Arterial Pressure [24 hours post-operative]

      Organ perfusion pressure measured as Mean Arterial Pressure (MAP). It will be measured hourly for 24 postoperative hours for all subjects and compared between the two study groups over the whole time of observation as the main between-group effect in panel regression.

    3. Hemodynamics as Characterized by Transpulmonary Pressure Gradient [24 hours post-operative]

      The transpulmonary pressure gradient (TPG), defined as the difference between mean pulmonary arterial pressure (Ppa) and left/common atrial (common atrial) pressure (Pla) will be measured hourly for 24 postoperative hours for all subjects and compared between the two study groups over the whole time of observation as the main between-group effect in panel regression.

    Secondary Outcome Measures

    1. Renal Dysfunction as Characterized by Change in Cystatin Level [from baseline pre-cardiopulmonary bypass to 24 hours post-operative]

      Cystatin levels will be measured at baseline (immediately before cardiopulmonary bypass) 24 hours postoperative. The change (postoperative minus baseline) in cystatin level will be compared between groups.

    2. Liver Dysfunction as Characterized by Transaminase Levels [48 hours post-operative]

      Transaminase levels (alanine and aspartate, measured in IU/L ) will be tracked for all patients and changes will be compared between study groups.

    Other Outcome Measures

    1. Resource Utilization Measured by Length of Stay (LOS) [from time of operation until hospital discharge]

      Length of stay (LOS) measured in postoperative hours compared between groups

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Weeks to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Planned completion of Fontan palliation

    • English or Spanish speaking

    • Completion of Informed Consent

    Exclusion Criteria:

    • Previous failed attempts at Fontan completion with subsequent takedown

    • Planned concomitant atrioventricular valvuloplasty or neoaortic valve or arch reconstruction at the time of Fontan completion

    • History of renal failure requiring renal replacement therapy

    • Absence of informed consent

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Medical College of Wisconsin

    Investigators

    • Principal Investigator: George Hoffman, MD, Medical College of Wisconsin

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Amee Bigelow, Professor, Medical College of Wisconsin
    ClinicalTrials.gov Identifier:
    NCT03088345
    Other Study ID Numbers:
    • IRBNet 885148
    First Posted:
    Mar 23, 2017
    Last Update Posted:
    Jul 7, 2020
    Last Verified:
    Jun 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Amee Bigelow, Professor, Medical College of Wisconsin
    Fontan Palliation Surgery
    Post-Operative Care
    Additional relevant MeSH terms:
    Heart Diseases
    Heart Defects, Congenital
    Univentricular Heart
    Vasopressins
    Arginine Vasopressin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Vasopressin, Arginine Placebo
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    Period Title: Overall Study
    STARTED 10 10
    COMPLETED 10 10
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Vasopressin, Arginine Placebo Total
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Total of all reporting groups
    Overall Participants 10 10 20
    Age (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    40
    (23)
    37
    (7)
    38
    (14)
    Sex: Female, Male (Count of Participants)
    Female
    3
    30%
    2
    20%
    5
    25%
    Male
    7
    70%
    8
    80%
    15
    75%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    10
    100%
    10
    100%
    20
    100%

    Outcome Measures

    1. Primary Outcome
    Title Hemodynamics as Characterized by Vasoactive Inotrope Score (VIS)
    Description The vasoactive inotrope score (VIS) is a linear sum of vasoactive and inotrope durg infusion doses. It is usually reported as dimensionless but is sometimes reported as normalized to dopamine mcg/kg/min equivalents. The score starts at 0 and has no defined upper limit, with a commonly observed range 0-50. It is used as a measure of the intensity of hemodynamic support, with higher scores indicating more vasoactive drug support for patients. The relationship of VIS to other patient outcomes is not consistent. It will be calculated hourly for all subjects and compared between groups over the entire observation timeframe.
    Time Frame 48 hours post-operative

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vasopressin, Arginine Placebo
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    Measure Participants 10 10
    Mean (Standard Deviation) [units]
    11
    (1.6)
    11.3
    (1.9)
    2. Primary Outcome
    Title Hemodynamics as Characterized by Mean Arterial Pressure
    Description Organ perfusion pressure measured as Mean Arterial Pressure (MAP). It will be measured hourly for 24 postoperative hours for all subjects and compared between the two study groups over the whole time of observation as the main between-group effect in panel regression.
    Time Frame 24 hours post-operative

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vasopressin, Arginine Placebo
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    Measure Participants 10 10
    Mean (Standard Deviation) [mmHg]
    67
    (1.3)
    66
    (1.1)
    3. Primary Outcome
    Title Hemodynamics as Characterized by Transpulmonary Pressure Gradient
    Description The transpulmonary pressure gradient (TPG), defined as the difference between mean pulmonary arterial pressure (Ppa) and left/common atrial (common atrial) pressure (Pla) will be measured hourly for 24 postoperative hours for all subjects and compared between the two study groups over the whole time of observation as the main between-group effect in panel regression.
    Time Frame 24 hours post-operative

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vasopressin, Arginine Placebo
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    Measure Participants 10 10
    Mean (Standard Deviation) [mmHg]
    6.4
    (0.5)
    8.3
    (0.5)
    4. Secondary Outcome
    Title Renal Dysfunction as Characterized by Change in Cystatin Level
    Description Cystatin levels will be measured at baseline (immediately before cardiopulmonary bypass) 24 hours postoperative. The change (postoperative minus baseline) in cystatin level will be compared between groups.
    Time Frame from baseline pre-cardiopulmonary bypass to 24 hours post-operative

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vasopressin, Arginine Placebo
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    Measure Participants 10 10
    Mean (95% Confidence Interval) [mg/L]
    0.095
    0.017
    5. Secondary Outcome
    Title Liver Dysfunction as Characterized by Transaminase Levels
    Description Transaminase levels (alanine and aspartate, measured in IU/L ) will be tracked for all patients and changes will be compared between study groups.
    Time Frame 48 hours post-operative

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vasopressin, Arginine Placebo
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    Measure Participants 10 10
    Mean (Standard Deviation) [iU/L]
    715
    (653)
    522
    (397)
    6. Other Pre-specified Outcome
    Title Resource Utilization Measured by Length of Stay (LOS)
    Description Length of stay (LOS) measured in postoperative hours compared between groups
    Time Frame from time of operation until hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vasopressin, Arginine Placebo
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    Measure Participants 10 10
    Mean (Standard Deviation) [hours]
    180
    (72)
    203
    (72)

    Adverse Events

    Time Frame 1 month
    Adverse Event Reporting Description
    Arm/Group Title Vasopressin, Arginine Placebo
    Arm/Group Description Patients randomized to this arm will receive a continuous arginine vasopressin infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Vasopressin, Arginine: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period. Patients randomized to this arm will receive a continuous normal saline infusion immediately following the modified ultrafiltration (MUF) period of their cardiac surgery. Placebos: Subjects will be started on a blinded continuous infusion of study drug/placebo in the OR, immediately following the completion of the MUF at 0.3 mU/kg/min. All caregivers will be blinded to the arm assignment. The infusion will run for 20 hours, at which time it will be weaned off at 0.1 mU/hr, over 3 hours.During the active study period, the care team will treat subjects per SOC, using any preferred medication to correct low cardiac output; there is no restriction on using open-label vasopressin during the active study treatment period.
    All Cause Mortality
    Vasopressin, Arginine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/10 (0%) 0/10 (0%)
    Serious Adverse Events
    Vasopressin, Arginine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/10 (0%) 0/10 (0%)
    Other (Not Including Serious) Adverse Events
    Vasopressin, Arginine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/10 (0%) 0/10 (0%)

    Limitations/Caveats

    The study design represents experience at a single center and may have limited generalizability. This study was underpowered to detect differences in many clinical outcomes.

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Amee Bigelow
    Organization Medical College of Wisconsin/Children's Hospital of Wisconsin
    Phone 5136364200
    Email amee.bigelow@cchmc.org
    Responsible Party:
    Amee Bigelow, Professor, Medical College of Wisconsin
    ClinicalTrials.gov Identifier:
    NCT03088345
    Other Study ID Numbers:
    • IRBNet 885148
    First Posted:
    Mar 23, 2017
    Last Update Posted:
    Jul 7, 2020
    Last Verified:
    Jun 1, 2020