Methylene Blue as a Third-line Vasopressor in Septic Shock

Carilion Clinic

Status and phase: Enrolling; Phase 2

Conditions: Septic Shock

Treatments: Drug: Methylene Blue; Drug: Phenylephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT04089072

IRB 19-549

Details and patient eligibility

About

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

Full 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).

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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®.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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250 participants in 2 patient groups

Control group

Experimental group

Description:

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.

Treatment:

Drug: Phenylephrine

Intervention group

Experimental group

Description:

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.

Treatment:

Drug: Methylene Blue