Trial Outcomes & Findings for MEthylene Blue In Patients With Acquired Methemoglobinemia (NCT NCT03395223)

Last Updated: 2023-04-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

7 participants

Primary outcome timeframe

1 hour

Results posted on

2023-04-10

Participant Flow

Recruitment period was from July 2018- August 2020. There were 13 hospital/urgent care sites initiated in France, the United Kingdom (UK), and the United States (US).

Participant milestones

Participant milestones
Measure	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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Overall Study STARTED	7
Overall Study Treatment Completed	7
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Overall Study Lost to Follow-up	3
Overall Study Other	1

Baseline Characteristics

One patient did not have a baseline methemoglobin result.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ProvayBlue (Methylene Blue) Arm n=7 Participants 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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Race (NIH/OMB) More than one race	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants
Region of Enrollment France	6 participants n=7 Participants
Region of Enrollment United States	1 participants n=7 Participants
Baseline methemoglobin	40.7 percentage of methemoglobin in blood STANDARD_DEVIATION 21.2 • n=6 Participants • One patient did not have a baseline methemoglobin result.
Age, Categorical <=18 years	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=7 Participants
Age, Categorical >=65 years	0 Participants n=7 Participants
Age, Continuous	44.3 years STANDARD_DEVIATION 17.2 • n=7 Participants
Sex: Female, Male Female	2 Participants n=7 Participants
Sex: Female, Male Male	5 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	1 Participants n=7 Participants
Race (NIH/OMB) White	6 Participants n=7 Participants

PRIMARY outcome

Timeframe: 1 hour

Population: The efficacy analysis set includes all safety analysis set patients who have at least 1 metHb assessment before and after ProvayBlue infusion

Outcome measures

Outcome measures
Measure	ProvayBlue (Methylene Blue) Arm n=6 Participants 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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Primary Efficacy Endpoint: Number of Participants With and Without 50% Reduction in metHb Level 50% reduction in metHb level within 1 hour of the first dose: Yes	3 Participants
Primary Efficacy Endpoint: Number of Participants With and Without 50% Reduction in metHb Level 50% reduction in metHb level within 1 hour of the first dose: No	3 Participants

SECONDARY outcome

Timeframe: 2 hours

Population: All Patients who received study drug

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.

Outcome measures

Outcome measures
Measure	ProvayBlue (Methylene Blue) Arm n=7 Participants 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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Number of Participants With and Without Concomitant Normalization of Respiratory Rate Respiratory rate normalized within 2 hours: Yes	2 Participants
Number of Participants With and Without Concomitant Normalization of Respiratory Rate Respiratory rate normalized within 2 hours: No	2 Participants
Number of Participants With and Without Concomitant Normalization of Respiratory Rate N/A (normal at baseline or no measurement within 2 hours of first dose)	3 Participants

SECONDARY outcome

Timeframe: 2 hours

Population: All participants who received study drug

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.

Outcome measures

Outcome measures
Measure	ProvayBlue (Methylene Blue) Arm n=7 Participants 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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Number of Participants With and Without Concomitant Normalization of Heart Rate Heart rate normalized within 2 hours of first dose: Yes	2 Participants
Number of Participants With and Without Concomitant Normalization of Heart Rate Heart rate normalized within 2 hours of first dose: No	1 Participants
Number of Participants With and Without Concomitant Normalization of Heart Rate N/A (normal at baseline or no measurement within 2 hours post first dose)	4 Participants

SECONDARY outcome

Timeframe: 2 hours

Population: All participants who received a dose of study drug

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.

Outcome measures

Outcome measures
Measure	ProvayBlue (Methylene Blue) Arm n=7 Participants 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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Number of Participants With and Without Concomitant Normalization of Blood Pressure Systolic BP · normalized within 2 hours of the first dose of ProvayBlue: Yes	2 Participants
Number of Participants With and Without Concomitant Normalization of Blood Pressure Systolic BP · normalized within 2 hours of the first dose of ProvayBlue: No	0 Participants
Number of Participants With and Without Concomitant Normalization of Blood Pressure Systolic BP · N/A (Normal at baseline or no measurement within 2 hours of the first dose)	5 Participants
Number of Participants With and Without Concomitant Normalization of Blood Pressure Diastolic BP · normalized within 2 hours of the first dose of ProvayBlue: Yes	0 Participants
Number of Participants With and Without Concomitant Normalization of Blood Pressure Diastolic BP · normalized within 2 hours of the first dose of ProvayBlue: No	1 Participants
Number of Participants With and Without Concomitant Normalization of Blood Pressure Diastolic BP · N/A (Normal at baseline or no measurement within 2 hours of the first dose)	6 Participants

SECONDARY outcome

Timeframe: 1 hour

Population: Only 1 patient received a second dose of ProvayBlue and they did not have a metHb measurement within 1 hour of that second dose

Evaluation of the patients who achieve a 50% reduction in metHb level after a second dose of ProvayBlue

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours

Population: All participants who received at least one dose of study drug

Number of participants who experience a treatment emergent adverse event assessed by the investigator as being related to study drug..

Outcome measures

Outcome measures
Measure	ProvayBlue (Methylene Blue) Arm n=7 Participants 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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Number of Participants With Treatment-related Adverse Events Related treatment emergent adverse event: yes	0 Participants
Number of Participants With Treatment-related Adverse Events Related treatment emergent adverse event: No	7 Participants

SECONDARY outcome

Timeframe: 24 hours

Population: Due to the nature of the disease, treatment with ProvayBlue was per the investigator's standard care and may have occurred prior to the informed consent document (PICD) being signed. However, data collection and study-specific assessments were to take place only after ICD signature. This often prevented collection of pharmacokinetic (PK) blood draws as informed consent was often given after the blood draws were to have been completed. As a result there were no patients with evaluable PK data.

Blood samples will be analyzed for methylene blue content

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours

Blood samples will be analyzed for Azure B content

Outcome measures

Outcome data not reported

Adverse Events

ProvayBlue (Methylene Blue) Arm

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ProvayBlue (Methylene Blue) Arm n=7 participants at risk 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. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia
Vascular disorders Thrombosis	14.3% 1/7 • Number of events 1 • AEs reported after the first dose infusion start time and within 10 days after the last dose treatment were collected.
Blood and lymphatic system disorders Methaemoglobinaemia	14.3% 1/7 • Number of events 1 • AEs reported after the first dose infusion start time and within 10 days after the last dose treatment were collected.

Other adverse events

Adverse event data not reported

Additional Information

Emilie HUYGHUES

Provepharm SAS

Phone: +33 6 20 58 28 27

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60