Methylene Blue as a Third-line Vasopressor in Septic Shock

Phase 2

Recruiting

• Conditions: Septic Shock
• Interventions: Drug: Methylene Blue; Drug: Phenylephrine

• Registration Number: NCT04089072
• Lead Sponsor: Carilion Clinic

Brief Summary

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

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 Timeline

• Study First Submitted: 2019-08-23
• Study First Submitted QC: 2019-09-12
• Study First Posted: 2019-09-13
• Study Start: 2019-12-01
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-22
• Last Update Posted: 2022-07-26
• Primary Completion: 2024-10-01
• Study Completion: 2024-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Methylene Blue	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.
Control group	Phenylephrine	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.

Primary Outcome Measures

Name	Time	Method
Change in mean arterial pressure	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of acute kidney injury requiring dialysis	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.

Trial Locations

Locations (1)

Carilion Clinic; 🇺🇸 Roanoke, Virginia, United States