Methylene Blue as a Third-line Vasopressor in Septic Shock

NCT04089072 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: IRB 19-549
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, prospective study comparing ProvayBlue® to standard care with multiple sympathomimetic vasopressors.

Conditions

Septic Shock

Keywords

Methylene Blue; Vasopressors; Septic Shock; Provay Blue®

Outcome Measures

Primary Outcomes (1)

• Change in mean arterial pressure

  The primary objective is to determine if the administration of ProvayBlue® is non-inferior to the use of phenylephrine as a third-line vasopressor to keep a mean arterial pressure (MAP)\>65 mmhg after one hour and at 24 hours after the initiation of the drugs.

  One hour and 24 hours after dose

Secondary Outcomes (1)

• Incidence of acute kidney injury requiring dialysis

  through time of patient discharge, an average of 8 days after admission

Study Arms (2)

Control group

EXPERIMENTAL

Patients in the control group will have phenylephrine infusion starting at 50 mcg/min and titrated to maintain a MAP \>65 mmHg as a third line vasopressor. Maximum dose of Phenylephrine is 300 mcg/min.

Drug: Phenylephrine

Intervention group

EXPERIMENTAL

Patients enrolled in the intervention group will receive 2 mg/kg IBW (Ideal Body Weight) bolus, given over 15 mins, of ProvayBlue® followed by a concomitant infusion at 2 mg/kg/hr (IBW) mixed in D5W, which will continue for 24 hours. ProvayBlue® ( Methylene Blue) will be used as the third-line vasopressor.

Drug: Methylene Blue

Interventions

Methylene Blue DRUG

Prior to the initiation of the randomized treatment, the subject will have received 2 vasopressors ( norepinephrine and vasopressin), they will be initiated on IV hydrocortisone . Once the patient is unable to maintain a mean arterial pressure of \>65mmHg and the hydrocortisone has been administered there will be an addition of a third-line vasopressor. Patients enrolled in the intervention group will receive ProvayBlue® and Patients enrolled in the control group will receive Phenylephrine infusion as a third line vasopressor in the treatment of septic shock.

Also known as: ProvayBlue®

Intervention group

Phenylephrine DRUG

Prior to the initiation of the randomized treatment, the subject will have received 2 vasopressors ( norepinephrine and vasopressin) already , they will be initiated on IV hydrocortisone . Once the patient is unable to maintain a mean arterial pressure of \>65mmHg and the hydrocortisone has been administered there will be an addition of a third-line vasopressor. Patients enrolled in the intervention group will receive ProvayBlue® and Patients enrolled in the control group will receive Phenylephrine infusion as a third line vasopressor in the treatment of septic shock.

Control group

Eligibility Criteria

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

You may qualify if:

• \. Meets Sepsis-3 Criteria (Suspected source of infection plus any 2 criteria of the qSOFA)
• Septic Shock (any patient requiring vasopressor therapy to maintain MAP \>65 mmHg or any patient with serum lactate \>2 mmol/dL even in the absence of hypovolemia ).
• \) Greater than 18 years old
• ) ICU Admission

You may not qualify if:

• Inability to obtain informed consent from an appropriate surrogate decision maker.
• Also:
• Children less than 18 years old
• Pregnant women or positive urinary pregnancy test in reproductive-aged women
• Prisoners
• Evolving myocardial infarction or known cardiomyopathy with documented EF\<35%
• Known grade 3 diastolic dysfunction document by echocardiogram
• Known hypersensitivity to thiazine dyes
• Pulmonary hypertension that is currently requiring vasodilator therapy
• Concurrent form of shock present or suspected: Obstructive, Neurogenic, Hemorrhagic
• Known documented history of G6PD deficiency or favism
• Active prior to admission medication prescription for a SSRI or SNRI , systemic heparin anticoagulation or other medications listed above (under Study Agent). These medications will be listed in the printed enrollment form.
• Severe renal failure is a contraindication to use of ProvayBlue®.

Sponsors & Collaborators

• Carilion Clinic: lead
• Provepharm Life Solutions: collaborator

Study Sites (1)

Carilion Clinic

Roanoke, Virginia, 24014, United States

RECRUITING

MeSH Terms

Conditions

Shock, Septic

Interventions

Methylene Blue; Phenylephrine

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Amines

Study Officials

• Frank Biscardi

  Carilion Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frank Biscardi, MD

CONTACT

540-981-7000; fhbiscardi@carilionclinic.org

Ruth Ndolo, RN

CONTACT

540-266-6557; rmndolo@carilionclinic.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: September 13, 2019
• Study Start: December 1, 2019
• Primary Completion: October 1, 2024
• Study Completion: November 1, 2024
• Last Updated: July 26, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)