Liver Transplant; Complications, Vasoplegic Syndrome
Conditions
Keywords
hydroxocobalamin, methylene blue
Brief summary
This study will evaluate if Hydroxocobalamin may be a new and possibly superior treatment for refractory vasoplegic syndrome during liver transplant surgery.
Interventions
DRUGHydroxocobalamin
Hydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes
DRUGMethylene Blue
Methylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, Open-Label, pilot study to describe the efficacy of hydroxocobalamin vs methylene blue
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients scheduled to undergo liver transplantation * Patients able to read and understand consent document (if patient is unable to provide an informed consent, the Legally Authorized Representative will be ask to consent on behalf of the patient). * SVR lower than 500 dynes-sec/cm-5 intraoperatively (this criterion must be met after consent intraoperatively)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Vascular Resistance (SVR) | 15, 30, 60, 90 and 120 minutes after initiation of treatment | SVR refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature. Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment. |
| Systolic Blood Pressure | 15, 30, 60, 90 and 120 minutes after initiation of treatment | Systolic blood pressure (top number of blood pressure reading). Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment. |
| Diastolic Blood Pressure | 15, 30, 60, 90 and 120 minutes after initiation of treatment | Diastolic blood pressure (bottom number of blood pressure reading). Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment. |
| Vasopressin | 15, 30, 60, 90 and 120 minutes after initiation of treatment | Vasopressin as measured by the total amount of vasopressors administered. Measured at 15, 30, 60, 90 and 120 minutes after initiation of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay | Up to 30 days after surgery | Total number of days subjects were admitted to the hospital |
| Post-operative Complications | Up to 30 days after surgery | The number of subjects to experience a death, cardiopulmonary event, Acute Kidney injury (AKI), Myocardial infarctions (MI), Stroke or Surgical and medical procedures - Other. |
| Post-operative Intensive Care Unit (ICU) Length of Stay | Up to 30 days after surgery | Total number of days subjects were admitted to the ICU |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cyanokit Single dose intraoperatively of Hydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes
Hydroxocobalamin: Hydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes | 9 |
| Methylene Blue Single dose intraoperatively of Methylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes
Methylene Blue: Methylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes | 10 |
| Total | 19 |
Baseline characteristics
| Characteristic | Cyanokit | Total | Methylene Blue |
|---|---|---|---|
| Age, Continuous | 65 years | 65 years | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 17 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 19 Participants | 10 Participants |
| Region of Enrollment United States | 9 participants | 19 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 15 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 1 / 10 |
| other Total, other adverse events | 1 / 9 | 2 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
Diastolic Blood Pressure
Diastolic blood pressure (bottom number of blood pressure reading). Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Population: The number of participants analyzed at each time point differs due to some participants completing their surgery earlier than others. Those participants were out of the surgical room by those time points and data was not collected nor analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cyanokit | Diastolic Blood Pressure | 30 minutes | 57 Millimeters of Mercury |
| Cyanokit | Diastolic Blood Pressure | 90 minutes | 60 Millimeters of Mercury |
| Cyanokit | Diastolic Blood Pressure | 60 minutes | 61 Millimeters of Mercury |
| Cyanokit | Diastolic Blood Pressure | 120 minutes | 59 Millimeters of Mercury |
| Cyanokit | Diastolic Blood Pressure | 15 minutes | 58 Millimeters of Mercury |
| Methylene Blue | Diastolic Blood Pressure | 120 minutes | 57 Millimeters of Mercury |
| Methylene Blue | Diastolic Blood Pressure | 15 minutes | 55 Millimeters of Mercury |
| Methylene Blue | Diastolic Blood Pressure | 30 minutes | 55 Millimeters of Mercury |
| Methylene Blue | Diastolic Blood Pressure | 60 minutes | 55 Millimeters of Mercury |
| Methylene Blue | Diastolic Blood Pressure | 90 minutes | 57 Millimeters of Mercury |
Primary
Systemic Vascular Resistance (SVR)
SVR refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature. Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Population: Data was not collected nor analyzed at all for one participant in the Methylene Blue arm. The number of participants analyzed at each time point differs due to some participants completing their surgery earlier than others. Those participants were out of the surgical room by those time points and data was not collected nor analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cyanokit | Systemic Vascular Resistance (SVR) | 30 minutes | 588 dyne*sec/cm^5 |
| Cyanokit | Systemic Vascular Resistance (SVR) | 90 minutes | 571 dyne*sec/cm^5 |
| Cyanokit | Systemic Vascular Resistance (SVR) | 60 minutes | 650 dyne*sec/cm^5 |
| Cyanokit | Systemic Vascular Resistance (SVR) | 120 minutes | 543 dyne*sec/cm^5 |
| Cyanokit | Systemic Vascular Resistance (SVR) | 15 minutes | 480 dyne*sec/cm^5 |
| Methylene Blue | Systemic Vascular Resistance (SVR) | 120 minutes | 415 dyne*sec/cm^5 |
| Methylene Blue | Systemic Vascular Resistance (SVR) | 15 minutes | 410 dyne*sec/cm^5 |
| Methylene Blue | Systemic Vascular Resistance (SVR) | 30 minutes | 420 dyne*sec/cm^5 |
| Methylene Blue | Systemic Vascular Resistance (SVR) | 60 minutes | 480 dyne*sec/cm^5 |
| Methylene Blue | Systemic Vascular Resistance (SVR) | 90 minutes | 530 dyne*sec/cm^5 |
Primary
Systolic Blood Pressure
Systolic blood pressure (top number of blood pressure reading). Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Population: The number of participants analyzed at each time point differs due to some participants completing their surgery earlier than others. Those participants were out of the surgical room by those time points and data was not collected nor analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cyanokit | Systolic Blood Pressure | 30 minutes | 113 Millimeters of Mercury |
| Cyanokit | Systolic Blood Pressure | 90 minutes | 129 Millimeters of Mercury |
| Cyanokit | Systolic Blood Pressure | 60 minutes | 120 Millimeters of Mercury |
| Cyanokit | Systolic Blood Pressure | 120 minutes | 116 Millimeters of Mercury |
| Cyanokit | Systolic Blood Pressure | 15 minutes | 109 Millimeters of Mercury |
| Methylene Blue | Systolic Blood Pressure | 120 minutes | 109 Millimeters of Mercury |
| Methylene Blue | Systolic Blood Pressure | 15 minutes | 110 Millimeters of Mercury |
| Methylene Blue | Systolic Blood Pressure | 30 minutes | 101 Millimeters of Mercury |
| Methylene Blue | Systolic Blood Pressure | 60 minutes | 111 Millimeters of Mercury |
| Methylene Blue | Systolic Blood Pressure | 90 minutes | 111 Millimeters of Mercury |
Primary
Vasopressin
Vasopressin as measured by the total amount of vasopressors administered. Measured at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cyanokit | Vasopressin | 30 minutes | 0.04 milli-units/kg/min |
| Cyanokit | Vasopressin | 90 minutes | 0.00 milli-units/kg/min |
| Cyanokit | Vasopressin | 60 minutes | 0.00 milli-units/kg/min |
| Cyanokit | Vasopressin | 120 minutes | 0.00 milli-units/kg/min |
| Cyanokit | Vasopressin | 15 minutes | 0.04 milli-units/kg/min |
| Methylene Blue | Vasopressin | 120 minutes | 0.00 milli-units/kg/min |
| Methylene Blue | Vasopressin | 15 minutes | 0.04 milli-units/kg/min |
| Methylene Blue | Vasopressin | 30 minutes | 0.04 milli-units/kg/min |
| Methylene Blue | Vasopressin | 60 minutes | 0.02 milli-units/kg/min |
| Methylene Blue | Vasopressin | 90 minutes | 0.00 milli-units/kg/min |
Secondary
Hospital Length of Stay
Total number of days subjects were admitted to the hospital
Time frame: Up to 30 days after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cyanokit | Hospital Length of Stay | 7 days |
| Methylene Blue | Hospital Length of Stay | 7 days |
Secondary
Post-operative Complications
The number of subjects to experience a death, cardiopulmonary event, Acute Kidney injury (AKI), Myocardial infarctions (MI), Stroke or Surgical and medical procedures - Other.
Time frame: Up to 30 days after surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyanokit | Post-operative Complications | Death | 1 participants |
| Cyanokit | Post-operative Complications | Cardiopulmonary Event | 0 participants |
| Cyanokit | Post-operative Complications | AKI | 0 participants |
| Cyanokit | Post-operative Complications | MI | 0 participants |
| Cyanokit | Post-operative Complications | Stroke | 0 participants |
| Cyanokit | Post-operative Complications | Surgical and medical procedures - Other. | 1 participants |
| Methylene Blue | Post-operative Complications | Stroke | 0 participants |
| Methylene Blue | Post-operative Complications | Death | 1 participants |
| Methylene Blue | Post-operative Complications | MI | 0 participants |
| Methylene Blue | Post-operative Complications | Cardiopulmonary Event | 1 participants |
| Methylene Blue | Post-operative Complications | Surgical and medical procedures - Other. | 1 participants |
| Methylene Blue | Post-operative Complications | AKI | 0 participants |
Secondary
Post-operative Intensive Care Unit (ICU) Length of Stay
Total number of days subjects were admitted to the ICU
Time frame: Up to 30 days after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cyanokit | Post-operative Intensive Care Unit (ICU) Length of Stay | 1 days |
| Methylene Blue | Post-operative Intensive Care Unit (ICU) Length of Stay | 0 days |