MEthylene Blue In Patients With Acquired Methemoglobinemia

Study Overview
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Brief Summary
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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.

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

Conditions
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Acquired Methaemoglobinaemia

Intervention / Treatment
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* Drug: Methylene Blue


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ProvayBlue (Methylene Blue) arm<br>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<br>* Administration of Methylene Blue to treat acquired methaemoglobinaemia<br>* Other names: ProvayBlue;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acquired Methaemoglobinemia, Methylene Blue