Methylene Blue as a Third-line Vasopressor in Septic Shock

July 22, 2022 updated by: Frank H Biscardi, Carilion Clinic

Methylene Blue as a Third-line Vasopressor in Septic Shock to Maintain Hemodynamics

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

Study Overview

Status

Recruiting

Conditions

Detailed Description

The study will be an un-blinded, Phase 2, randomized, 1:1, prospective trial comparing patients in septic shock receiving norepinephrine and vasopressin followed by phenylephrine versus ProvayBlue® as the third-line vasopressor. The third line vasopressor will be compared at 1 hour to see if it affects the patient's mean arterial blood pressure (MAP).

Study Type

Interventional

Enrollment (Anticipated)

250

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Virginia
      • Roanoke, Virginia, United States, 24014
        • Recruiting
        • Carilion Clinic
        • Contact:
          • Frank Biscardi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

1. Meets Sepsis-3 Criteria (Suspected source of infection plus any 2 criteria of the qSOFA)

2 .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 ).

3) Greater than 18 years old

4 ) ICU Admission

Exclusion Criteria:

Inability to obtain informed consent from an appropriate surrogate decision maker.

Also:

  1. Children less than 18 years old
  2. Pregnant women or positive urinary pregnancy test in reproductive-aged women
  3. Prisoners
  4. Evolving myocardial infarction or known cardiomyopathy with documented EF<35%
  5. Known grade 3 diastolic dysfunction document by echocardiogram
  6. Known hypersensitivity to thiazine dyes
  7. Pulmonary hypertension that is currently requiring vasodilator therapy
  8. Concurrent form of shock present or suspected: Obstructive, Neurogenic, Hemorrhagic
  9. Known documented history of G6PD deficiency or favism
  10. 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.
  11. Severe renal failure is a contraindication to use of ProvayBlue®.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Control group
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.

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.

Experimental: Intervention group
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.

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.

Other Names:
  • ProvayBlue®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mean arterial pressure
Time Frame: One hour and 24 hours after dose
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of acute kidney injury requiring dialysis
Time Frame: through time of patient discharge, an average of 8 days after admission
The secondary objectives are to see if the total vasopressor dosing and renal replacement needs are different in those patients receiving ProvayBlue® rather than standard care with escalating number of vasopressors.
through time of patient discharge, an average of 8 days after admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Frank Biscardi, Carilion Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2019

Primary Completion (Anticipated)

October 1, 2024

Study Completion (Anticipated)

November 1, 2024

Study Registration Dates

First Submitted

August 23, 2019

First Submitted That Met QC Criteria

September 12, 2019

First Posted (Actual)

September 13, 2019

Study Record Updates

Last Update Posted (Actual)

July 26, 2022

Last Update Submitted That Met QC Criteria

July 22, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

To publish aggregated data

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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