Trial Outcomes & Findings for Early Use of Vasopressin in Post-Fontan Management (NCT NCT03088345)

NCT ID: NCT03088345

Last Updated: 2020-07-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 20 participants
• Primary outcome timeframe: 48 hours post-operative
• Results posted on: 2020-07-07

Participant Flow

Participant milestones

Measure	Vasopressin, Arginine 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.	Placebo 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.
Overall Study STARTED	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Vasopressin, Arginine n=10 Participants 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.	Placebo n=10 Participants 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 n=20 Participants Total of all reporting groups
Age, Continuous	40 months STANDARD_DEVIATION 23 • n=10 Participants	37 months STANDARD_DEVIATION 7 • n=10 Participants	38 months STANDARD_DEVIATION 14 • n=20 Participants
Sex: Female, Male Female	3 Participants n=10 Participants	2 Participants n=10 Participants	5 Participants n=20 Participants
Sex: Female, Male Male	7 Participants n=10 Participants	8 Participants n=10 Participants	15 Participants n=20 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	10 participants n=10 Participants	10 participants n=10 Participants	20 participants n=20 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Vasopressin, Arginine n=10 Participants 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.	Placebo n=10 Participants 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.
Hemodynamics as Characterized by Vasoactive Inotrope Score (VIS)	11 units Standard Deviation 1.6	11.3 units Standard Deviation 1.9

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Vasopressin, Arginine n=10 Participants 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.	Placebo n=10 Participants 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.
Hemodynamics as Characterized by Mean Arterial Pressure	67 mmHg Standard Deviation 1.3	66 mmHg Standard Deviation 1.1

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Vasopressin, Arginine n=10 Participants 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.	Placebo n=10 Participants 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.
Hemodynamics as Characterized by Transpulmonary Pressure Gradient	6.4 mmHg Standard Deviation 0.5	8.3 mmHg Standard Deviation 0.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Vasopressin, Arginine n=10 Participants 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.	Placebo n=10 Participants 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.
Renal Dysfunction as Characterized by Change in Cystatin Level	0.095 mg/L Interval -0.086 to 0.277	0.017 mg/L Interval -0.16 to 0.194

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Vasopressin, Arginine n=10 Participants 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.	Placebo n=10 Participants 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.
Liver Dysfunction as Characterized by Transaminase Levels	715 iU/L Standard Deviation 653	522 iU/L Standard Deviation 397

OTHER_PRE_SPECIFIED outcome

Timeframe: from time of operation until hospital discharge

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

Outcome measures

Measure	Vasopressin, Arginine n=10 Participants 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.	Placebo n=10 Participants 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.
Resource Utilization Measured by Length of Stay (LOS)	180 hours Standard Deviation 72	203 hours Standard Deviation 72

Adverse Events

Vasopressin, Arginine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Amee Bigelow

Medical College of Wisconsin/Children's Hospital of Wisconsin

Phone: 5136364200

Email: amee.bigelow@cchmc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place