Hemodynamic Effects of Methylene Blue vs Hydroxocobalamin in Patients at Risk of Vasoplegia During Cardiac Surgery

NCT03446599 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: D17173
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study to determine the hemodynamic effects when hydroxocobalamin vs methylene blue is administered during cardiopulmonary bypass in patients at risk of vasoplegia by measuring mean arterial pressure (MAP), systemic vascular resistance (SVR) and vasopressor requirement.

Conditions

Vasoplegia; Hypotension; Coronary Artery Disease; Cardiac Valve Disease

Keywords

cardiac surgery; vasoplegia; cardiopulmonary bypass

Outcome Measures

Primary Outcomes (1)

• ΔMAP (baseline to 30 min after CPB separation) in OH-CO and placebo groups.

  Our primary outcome measure is the change in MAP between one of the treatment (hydroxocobalamin) and placebo groups measured at 30 minutes post-CPB

  From baseline to 30 minutes after successful separation from cardiopulmonary bypass (CPB)

Secondary Outcomes (8)

• ΔMAP (baseline to 30 min after CPB separation) in OH-CO and MB groups.

  From baseline to 30 minutes after successful separation from cardiopulmonary bypass (CPB)

• ΔMAP between baseline and all time points (30 and 60 minutes after CPB initiation, and 30 and 60 minutes after CPB separation) between all 3 groups.

  From baseline to all measured time points (30 and 60 minutes after CPB initiation, and 30 and 60 minutes after CPB separation).

• ΔSVR (baseline to 30 min after CPB separation) in OH-CO and placebo groups.

  From baseline to 30 minutes after successful separation from cardiopulmonary bypass (CPB)

• ΔSVR (baseline to 30 min after CPB separation) in OH-CO and MB groups.

  From baseline to 30 minutes after successful separation from cardiopulmonary bypass (CPB)

• ΔSVR between baseline and all time points (30 and 60 minutes after CPB initiation, and 30 and 60 minutes after CPB separation) between all 3 groups.

  From baseline to all measured time points (30 and 60 minutes after CPB initiation, and 30 and 60 minutes after CPB separation).

Study Arms (3)

Hydroxocobalamin

EXPERIMENTAL

Participants in this arm will receive one intravenous 5-gram dose of hydroxocobalamin reconstituted in 200ml of normal saline over 10-15minutes at the time of initiation of cardiopulmonary bypass.

Drug: Hydroxocobalamin

Methyelene blue

EXPERIMENTAL

Participants in this arm will receive one intravenous 2mg/kg dose of methylene blue diluted in 200ml of normal saline over 10-15minutes at the time of initiation of cardiopulmonary bypass.

Drug: Methylene Blue

Normal saline

PLACEBO COMPARATOR

Participants in this arm will receive an intravenous administration of 200ml normal saline over 10-15minutes at the time of initiation of cardiopulmonary bypass.

Drug: Normal saline

Interventions

Hydroxocobalamin DRUG

One intravenous dose of 5mg hydroxocobalamin, which is the current FDA-approved adult dose for carbon monoxide poisoning, reconstituted in 200ml normal saline will be administered over 10-15minutes at the time of initiation of cardiopulmonary bypass.

Hydroxocobalamin

Methylene Blue DRUG

One intravenous dose of methylene blue 2mg/kg, which has been the accepted dose for vasoplegia, diluted in 200ml normal saline will be administered over 10-15minutes at the time of initiation of cardiopulmonary bypass.

Methyelene blue

Normal saline DRUG

200ml normal saline will be administered intravenously over 10-15minutes at the time of initiation of cardiopulmonary bypass.

Normal saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients \> 18 years of age
• undergoing coronary artery bypass grafting (CABG) and/or valve surgery on cardiopulmonary bypass (CPB)
• who have 2 or more preoperative risk factors for vasoplegia1-6:
• angiotensin-converting enzyme (ACE)-inhibitor, beta-blocker or amiodarone use within 24 hours of surgery
• anticipated CPB duration greater than 120minutes (combined CABG and valve procedure, \>3 planned grafts, \> 2 valve surgery)
• baseline left ventricular ejection fraction (LVEF) of less than 40%.

You may not qualify if:

• Emergency surgery
• Severe renal insufficiency (preoperative Cr \> 1.8)
• Severe hepatic disease (preoperative diagnosis of liver cirrhosis, or recent elevated liver function tests)
• Pregnancy or women of childbearing potential
• Known hypersensitivity to hydroxocobalamin or cyanocobalamin
• Known hypersensitivity to methylene blue
• Other known contraindications to methylene blue use: glucose-6-phosphate dehydrogenase (G6PD) deficiency, or ongoing selective serotonin reuptake inhibitor (SSRI), selective norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA) or monoamine inhibitor (MAOi) use.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Vasoplegia; Hypotension; Coronary Artery Disease; Heart Valve Diseases

Interventions

Hydroxocobalamin; Methylene Blue; Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Vitamin B 12; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Masking is unfortunately not feasible due to characteristic side effects from each medication that alert most healthcare providers to its presence: methylene blue - transient interference with pulse oximetry, blue chromaturia; hydroxocobalamin - red chromaturia.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: February 20, 2018
• First Posted: February 27, 2018
• Study Start: November 1, 2019
• Primary Completion: May 1, 2020
• Study Completion: June 30, 2020
• Last Updated: March 2, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)