Vasoplegic Syndrome
Conditions
Keywords
Vitamin B12a, Hypotension, Cardiopulmonary Bypass
Brief summary
The study team will evaluate the medication Hydroxocobalamin (B12a) for treatment of low blood pressure after cardiac surgery.
Detailed description
If subjects meet the criteria for inclusion in the study based on the subjects blood pressure the subject will be randomized to receive the study drug or a placebo. Subjects blood pressure will be monitored closely for the first 30 minutes and then have standard intensive care unit (ICU) care afterwards. Kidney dysfunction will be assessed for changes in urine production and laboratory values that are followed as a part of standard postoperative care. Study coordinators will obtain these values from subjects medical records for 7 days and subjects will be contacted by phone for follow up after 30 days.
Interventions
DRUGHydroxocobalamin
5g, IV, Infused once over 15 minutes. The drug comes in a 250ml glass vial with 5g of lyophilized hydroxocobalamin to be reconstituted in 200ml of Normal Saline, Dextrose or Lactated Ringers.
PROCEDURECardiopulmonary Bypass
Technique that temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the patient's body.
DRUGPlacebos
Placebo is a Normal Saline, 5g, IV, Infused once over 15 minutes. The placebo comes in a 250ml glass vial.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Masking and blinding will be carried out by the research pharmacy with unmasking to be performed at study completion through the research pharmacy and statistician.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Any patient for whom we are able to obtain consent ahead of their procedure * Patients presenting for a procedure in which cardiopulmonary bypass will be required * Considered high risk for vasoplegic syndrome * Has no contraindications to arterial line or PA catheter placement * Develops high-dose vasopressors for 30 min or longer and refractory hypotension consistent with vasoplegic syndrome within 24 hours of coming off cardiopulmonary bypass.
Exclusion criteria
* Age\<18 years * Known pregnancy or patients without a documented pregnancy test if not menopausal. * Known prior anaphylactic or allergic reaction to B12a * CKD stage 4 or worse * ECMO (extracorporeal membrane oxygenation) prior to study consent. * Patients currently on cardiopulmonary bypass
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Arterial Pressure | baseline, 4 hours | The average pressure in a patient's arteries during one cardiac cycle |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Norepinephrine Equivalent Infusion Rate. Norepinephrine Equivalent Table is Listed in the Study Protocol | baseline, 4 hours | Vasopressors are administered and adjusted to maintain blood pressure. The combined dose of vasopressor dosage was calculated as norepinepheine equivalents listed in Table 1 of the protocol appendix and measured as a secondary outcome through the first 4 hours after intevention. |
| Change in Systolic Blood Pressure | baseline, 4 hours | The maximum arterial pressure during contraction of the left ventricle of the heart. |
| Death | 30 days | Number subject deaths |
| Duration of Hospital Stay | 30 days | Number of days subjects are hospitalized |
| Duration of Intensive Care Stay | 30 days | Number of days subjects are in the intensive care unit |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| B12a Subjects received Hydroxocobalamin marketed as Cyanokit®, 5g, IV
Hydroxocobalamin: 5g, IV, Infused once over 15 minutes. The drug comes in a 250ml glass vial with 5g of lyophilized hydroxocobalamin to be reconstituted in 200ml of Normal Saline, Dextrose or Lactated Ringers.
Cardiopulmonary Bypass: Technique that temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the patient's body. | 4 |
| Placebo Subjects received placebo
Cardiopulmonary Bypass: Technique that temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the patient's body.
Placebos: Placebo is a Normal Saline, 5g, IV, Infused once over 15 minutes. The placebo comes in a 250ml glass vial. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Total | B12a | Placebo |
|---|---|---|---|
| Age, Continuous | 69 years | 64 years | 70 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 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 | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 8 participants | 4 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 0 / 4 | 2 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
Change in Mean Arterial Pressure
The average pressure in a patient's arteries during one cardiac cycle
Time frame: baseline, 4 hours
Population: Terminated study. Insufficient recruitment over study period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| B12a | Change in Mean Arterial Pressure | 6 mmHg |
| Placebo | Change in Mean Arterial Pressure | -0.5 mmHg |
Secondary
Change in Norepinephrine Equivalent Infusion Rate. Norepinephrine Equivalent Table is Listed in the Study Protocol
Vasopressors are administered and adjusted to maintain blood pressure. The combined dose of vasopressor dosage was calculated as norepinepheine equivalents listed in Table 1 of the protocol appendix and measured as a secondary outcome through the first 4 hours after intevention.
Time frame: baseline, 4 hours
Population: Terminated study. Insufficient recruitment over study period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| B12a | Change in Norepinephrine Equivalent Infusion Rate. Norepinephrine Equivalent Table is Listed in the Study Protocol | -0.035 mcg/kg/min |
| Placebo | Change in Norepinephrine Equivalent Infusion Rate. Norepinephrine Equivalent Table is Listed in the Study Protocol | 0.02 mcg/kg/min |
Secondary
Change in Systolic Blood Pressure
The maximum arterial pressure during contraction of the left ventricle of the heart.
Time frame: baseline, 4 hours
Population: Terminated study. Insufficient recruitment over study period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| B12a | Change in Systolic Blood Pressure | 5.5 mmHg |
| Placebo | Change in Systolic Blood Pressure | 0.5 mmHg |
Secondary
Death
Number subject deaths
Time frame: 30 days
Population: Terminated study. Insufficient recruitment over study period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B12a | Death | 0 Participants |
| Placebo | Death | 0 Participants |
Secondary
Duration of Hospital Stay
Number of days subjects are hospitalized
Time frame: 30 days
Population: Terminated study. Insufficient recruitment over study period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| B12a | Duration of Hospital Stay | 11.5 days |
| Placebo | Duration of Hospital Stay | 15 days |
Secondary
Duration of Intensive Care Stay
Number of days subjects are in the intensive care unit
Time frame: 30 days
Population: Terminated study. Insufficient recruitment over study period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| B12a | Duration of Intensive Care Stay | 6 days |
| Placebo | Duration of Intensive Care Stay | 8.50 days |