Methylene Blue vs Cyanokit for Intraoperative Vasoplegic Syndrome in Liver Transplant Patients

The Efficacy of Intravenous Hydroxocobalamin Versus Methylene Blue as Treatment for Intraoperative Vasoplegic Syndrome in Liver Transplant Patients

This study will evaluate if Hydroxocobalamin may be a new and possibly superior treatment for refractory vasoplegic syndrome during liver transplant surgery.

Study Overview

• Status: Completed
• Conditions: Liver Transplant; Complications; Vasoplegic Syndrome
• Intervention / Treatment: Drug: Hydroxocobalamin; Drug: Methylene Blue

Detailed Description

This randomized, prospective, open label, pilot study will involve 20 LT patients with intraoperative vasoplegic syndrome. If vasoplegic syndrome is identified via SVR lower than 500 dynes-sec/cm-5, the patients will be randomized to receiving either IV methylene blue or hydroxocobalamin (10 patients in each group). The primary end point will examine the efficacy of the two medications on treating intraoperative vasoplegic syndrome. The SVR, blood pressure, and amount of administered vasopressors at 0, 15, 30, 60, 90, 120, 150, and 180 minutes after the medication administrations will be recorded. .

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyanokit; Single dose intraoperatively of Hydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes	Drug: Hydroxocobalamin; Hydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes
Active Comparator: Methylene Blue; Single dose intraoperatively of Methylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes	Drug: Methylene Blue; Methylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	15, 30, 60, 90 and 120 minutes after initiation of treatment
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.	15, 30, 60, 90 and 120 minutes after initiation of treatment
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.	15, 30, 60, 90 and 120 minutes after initiation of treatment
Vasopressin	Vasopressin as measured by the total amount of vasopressors administered. Measured at 15, 30, 60, 90 and 120 minutes after initiation of treatment.	15, 30, 60, 90 and 120 minutes after initiation of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Intensive Care Unit (ICU) Length of Stay	Total number of days subjects were admitted to the ICU	Up to 30 days after surgery
Hospital Length of Stay	Total number of days subjects were admitted to the hospital	Up to 30 days after surgery
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.	Up to 30 days after surgery

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Sher-Lu Pai, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2019
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): February 27, 2024

Study Registration Dates

• First Submitted: August 12, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: methylene blue; hydroxocobalamin
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Disease; Syndrome; Vasoplegia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin; Methylene Blue
• Other Study ID Numbers: 18-006247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan in place.

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