Vitamin B12a Vasoplegic Syndrome

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study for High-Dose Hydroxocobalamin (Vitamin B12A) for Vasopressor Refractory Hypotension Following Cardiopulmonary Bypass

The study team will evaluate the medication Hydroxocobalamin (B12a) for treatment of low blood pressure after cardiac surgery.

Study Overview

• Status: Terminated
• Conditions: Vasoplegic Syndrome
• Intervention / Treatment: Drug: Hydroxocobalamin; Procedure: Cardiopulmonary Bypass; Drug: Placebos

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Saint Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B12a; Subjects will receive Hydroxocobalamin marketed as Cyanokit®, 5g, IV	Drug: 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.; Other Names: Cyanokit®, Vitamin B12a; Procedure: 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.; Other Names: CPB
Placebo Comparator: Placebo; Subjects will receive placebo	Procedure: 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.; Other Names: CPB; Drug: Placebos; Placebo is a Normal Saline, 5g, IV, Infused once over 15 minutes. The placebo comes in a 250ml glass vial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Arterial Pressure	The average pressure in a patient's arteries during one cardiac cycle	baseline, 4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Systolic Blood Pressure	The maximum arterial pressure during contraction of the left ventricle of the heart.	baseline, 4 hours
Death	Number subject deaths	30 days
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.	baseline, 4 hours
Duration of Hospital Stay	Number of days subjects are hospitalized	30 days
Duration of Intensive Care Stay	Number of days subjects are in the intensive care unit	30 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: James A. Nelson, M.B.B.S., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2019
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (Actual): November 8, 2018

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 6, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Hypotension; Cardiopulmonary Bypass; Vitamin B12a
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Disease; Syndrome; Vasoplegia; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: 17-011130

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No