MEthylene Blue In Patients With Acquired Methemoglobinemia (MEBIPAM)

Open Label Clinical Study to Evaluate the Safety and Efficacy of ProvayBlueTM (Methylene Blue) for the Treatment of Acquired Methemoglobinemia

This is an open label, uncontrolled, Phase 4 study including 10 patients who present in hospital/urgent care setting with acquired methemoglobinemia. The population may include pediatric and adult patients (males and females of all ages are included).

The study will run in both the EU and the US. The aim of the study is to confirm safety and efficacy of ProvayBlueTM for the treatment of acquired methemoglobinemia and has been requested by the US-FDA as a Post-Marketing requirements.

Study Overview

• Status: Completed
• Conditions: Acquired Methaemoglobinaemia
• Intervention / Treatment: Drug: Methylene Blue

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75475
    • Hôpital Lariboisière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pediatric or adult patients (males and females of all ages are included) diagnosed with acquired methemoglobinemia and receiving treatment with ProvayBlue™ as per the treating physician's diagnosis and hospital standard of care.

Acquired methemoglobinemia is defined as a level of methemoglobinemia >30% or ≤30% in case of clinical symptoms (e.g. sleepiness, cyanosis, dizziness, etc.).

• Written informed consent obtained prior to any data collection (retrospective and prospective) for this study and study specific assessments.

Exclusion Criteria:

• Known severe hypersensitivity reactions to methylene blue or any other thiazine dye;
• Known deficiency in glucose-6-phosphate dehydrogenase (G6PD) due to the risk of hemolytic anemia as well as lack of therapeutic effect;
• Known deficiency in Nicotinamide Adenine Dinucleotide Phosphate Hydrogen (NADPH) reductase.
• Known use of selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), MonoAmine Oxidase (MAO) inhibitors or drugs metabolised via CYP isoenzymes anticipated during the treatment phase of the study.
• Women who refuse to stop breastfeeding for up to 8 days after receiving the last dose of ProvayBlueTM.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ProvayBlue (Methylene Blue) arm; Methylene Blue 0.5% will be administered. 1 mg/kg will be administered intravenously over 5-30 minutes. If methemoglobin level remains above 30% or if clinical symptoms persist, give a repeat dose of up to 1 mg/kg one hour after the first dose.	Drug: Methylene Blue; Administration of Methylene Blue to treat acquired methaemoglobinaemia; Other Names: ProvayBlue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Endpoint: Number of Participants With and Without 50% Reduction in metHb Level	A 50% reduction in metHb level within 1 hour of the first dose of ProvayBlue for treatment of acquired methemoglobinemia. The timing of postdosing metHb level assays is inconsistent in clinical practice, for that reason metHb level at 1-hour postdosing was derived using linear interpolation.	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With and Without Concomitant Normalization of Respiratory Rate	Normalization of the respiratory rate within 2 hours of the first dose of ProvayBlue. The normal range used for respiratory rate was 12-20 breaths per minute.	2 hours
Number of Participants With and Without Concomitant Normalization of Heart Rate	Normalization of the heart rate within 2 hours of the first dose of ProvayBlue. The normal range used for heart rate was 50-100 beats per minute.	2 hours
Number of Participants With and Without Concomitant Normalization of Blood Pressure	Normalization of blood pressure standard values within 2 hours of the first dose of ProvayBlue. The normal range used for systolic blood pressure was was 90-140 mm HG and the normal range used for diastolic blood pressure was 60-90 mm HG.	2 hours
Second Dose	Evaluation of the patients who achieve a 50% reduction in metHb level after a second dose of ProvayBlue	1 hour
Number of Participants With Treatment-related Adverse Events	Number of participants who experience a treatment emergent adverse event assessed by the investigator as being related to study drug..	24 hours
Methylene Blue Content in Blood Samples	Blood samples will be analyzed for methylene blue content	24 hours
Azure B Content in Blood Samples	Blood samples will be analyzed for Azure B content	24 hours

Collaborators and Investigators

• Sponsor: Provepharm SAS
• Investigators: Principal Investigator: Bruno Megarbane, Hôpital Lariboisière

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2018
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: January 9, 2018
• First Posted (Actual): January 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Methylene Blue; Acquired Methaemoglobinemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Methemoglobinemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: PVP-2016003; 2017-000290-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No