Acquired MethaemoglobinaemiaPhase 4MEBIPAMNCT03395223

MEthylene Blue In Patients With Acquired Methemoglobinemia

A Phase 4 study testing Methylene Blue in people with Acquired Methaemoglobinaemia, run by Provepharm SAS at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Any age
Conditions the study is for: Acquired Methaemoglobinaemia
What is being tested?: Methylene Blue
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteFrance
Study dates: 6 Jul 2018to 31 Aug 2020
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

France1 site

Hôpital Lariboisière
Paris, 75475

Other trials in France

About this study

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

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.

Conditions: Acquired Methaemoglobinaemia
Being tested: Methylene Blue
Keywords: Acquired Methaemoglobinemia, Methylene Blue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Methylene BlueDrug
Also called ProvayBlue
Administration of Methylene Blue to treat acquired methaemoglobinaemia

Study groups in NCT03395223
Study group	Role	What they receive
ProvayBlue (Methylene Blue) arm	Experimental	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. Receives: Drug: Methylene Blue

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 1 hour

Secondary outcomes (7)

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.
Measured: 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.
Measured: 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.
Measured: 2 hours
Second Dose
Evaluation of the patients who achieve a 50% reduction in metHb level after a second dose of ProvayBlue
Measured: 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..
Measured: 24 hours
Methylene Blue Content in Blood Samples
Blood samples will be analyzed for methylene blue content
Measured: 24 hours
Azure B Content in Blood Samples
Blood samples will be analyzed for Azure B content
Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Jul 201831 Aug 2020

First posted10 Jan 2018
Study start6 Jul 2018
Primary completion31 Aug 2020
Study completion31 Aug 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Acquired MethaemoglobinaemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03395223
Sponsor's protocol ID: PVP-2016003
Other IDs: 2017-000290-37, 2017
Acronym: MEBIPAM
Status last verified: Mar 2023
First submitted: 18 Dec 2017
Last updated: 10 Apr 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 10 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open Label Clinical Study to Evaluate the Safety and Efficacy of ProvayBlueTM (Methylene Blue) for the Treatment of Acquired Methemoglobinemia
ClinicalTrials.gov ID: NCT03395223
Acronym / sponsor ID: MEBIPAM / PVP-2016003
Conditions: Acquired Methaemoglobinaemia
Keywords: Acquired Methaemoglobinemia, Methylene Blue
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: Provepharm SASIndustry (pharma, biotech, devices)
Study start: 6 Jul 2018 (actual)
Primary completion: 31 Aug 2020 (actual)
Study completion: 31 Aug 2020 (actual)
First posted: 10 Jan 2018 (actual)
Results: Posted 10 Apr 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ProvayBlue (Methylene Blue) arm	Experimental	Drug: Methylene BlueMethylene 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.

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Methylene BlueAlso: ProvayBlueAdministration of Methylene Blue to treat acquired methaemoglobinaemia	Drug	ProvayBlue (Methylene Blue) arm

Primary outcome

Primary Efficacy Endpoint: Number of Participants With and Without 50% Reduction in metHb Level
Time frame: 1 hour
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.

7 secondary outcomes

Number of Participants With and Without Concomitant Normalization of Respiratory Rate
Time frame: 2 hours
Number of Participants With and Without Concomitant Normalization of Heart Rate
Time frame: 2 hours
Number of Participants With and Without Concomitant Normalization of Blood Pressure
Time frame: 2 hours
Second Dose
Time frame: 1 hour
Number of Participants With Treatment-related Adverse Events
Time frame: 24 hours
Methylene Blue Content in Blood Samples
Time frame: 24 hours
Azure B Content in Blood Samples
Time frame: 24 hours

Results and safety

Results posted to the registry on 10 Apr 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ProvayBlue (Methylene Blue) Arm	7	3

Primary outcome: Primary Efficacy Endpoint: Number of Participants With and Without 50% Reduction in metHb Level

Time frame: 1 hour. Count of participants. Unit: Participants

Measure	ProvayBlue (Methylene Blue) Arm n = 6
50% reduction in metHb level within 1 hour of the first dose: Yes	3
50% reduction in metHb level within 1 hour of the first dose: No	3

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

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs reported after the first dose infusion start time and within 10 days after the last dose treatment were collected.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ProvayBlue (Methylene Blue) Arm	2 of 7 (28.6%)	0 of 7 (0%)	0 of 7

Limitations and caveats (from the sponsor): This study experienced a slow pace of enrollment leading to enrollment being closed prior to completing enrollment of the planned sample size of 10 subjects. Additionally, the nature of the disease and indication, necessitated that the subject's treatment with ProvayBlue was per the investigator's standard care and could have occurred prior to or after the PICD was signed. This frequently prevented the collection of pharmacokinetic (PK) blood draws and study specific evaluations on schedule.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bruno Megarbane principal investigator

Hopital Lariboisière

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Methylene Blue in people with Acquired Methaemoglobinaemia, run by Provepharm SAS at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Efficacy Endpoint: Number of Participants With and Without 50% Reduction in metHb Level (time frame: 1 hour). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03395223.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2023.