Acquired Methemoglobinemia Observational Registry (metHb)

Use of Methylene Blue in Acquired Methemoglobinemia: Prospective Observational Registry (metHb)

This prospective, observational registry aims to collect real-world data regarding the safety and efficacy of ProvayBlue® (methylene blue 0.5%) used according to normal standard of care for the treatment of acquired methemoglobinemia. Methylene blue has been used for decades as a rescue medication for the treatment of methemoglobinemia, a rare and potentially life-threatening condition in which elevated levels of methemoglobin impede the delivery of oxygen from blood to body tissues. However, consistent prospective data about the safety and efficacy of this medication are sparse, simply because of the rarity of the disorder. ProvayBlue® received accelerated FDA approval for treatment of acquired methemoglobinemia in 2016. This large, prospective, multi-center observational registry has been initiated to gain more information on the use of methylene blue in the treatment of acquired methemoglobinemia.

Study Overview

• Status: Completed
• Conditions: Methemoglobinemia; Methemoglobinemia, Acquired
• Intervention / Treatment: Drug: Methylene Blue

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai
    • Sacramento, California, United States, 95817
      • UC Davis Health
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Bridgeport Hospital
    • Hartford, Connecticut, United States, 06106
      • Hartford Hospital
  • Florida
    • Palm Beach Gardens, Florida, United States, 33410
      • Palmetto General
    • Tampa, Florida, United States, 33606
      • Tampa General
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Health System
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Partners Healthcare; Brigham and Women's
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48236
      • St John Medical Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • HealthPartners Regions
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • New York, New York, United States, 10032
      • New York Methodist
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • University Hospitals
    • Youngstown, Ohio, United States, 44501
      • Mercy Health
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Health Science Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Houston Methodist
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients who present in hospital / urgent care setting diagnosed with acquired methemoglobinemia.

Description

Inclusion Criteria:

• Adult or pediatric patients diagnosed with acquired methemoglobinemia and receiving treatment with ProvayBlue® (methylene blue 0.5%) as per the treating physician's diagnosis and the acute care facility's standard of care
• Those acquired methemoglobinemia patients whose diagnosis is aided by measurement of methemoglobin and whose ongoing treatment is guided by re-measurement of methemoglobin ~1h post-treatment with ProvayBlue® in accordance with the US FDA Label prescribing information

Exclusion Criteria:

• Refusal of consent (in those subjects approached for consent where required by local institutional procedures)
• Treatment of methemoglobinemia with another methylene blue product

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Primary Treated Group; Subjects who are administered methylene blue for treatment of acquired methemoglobinemia that is symptomatic (eg, exhibiting sleepiness, cyanosis, dizziness, etc) or with measured methemoglobin levels > 30%.	Drug: Methylene Blue; Administration of methylene blue as per the treating physician's diagnosis and the acute care facility's standard of care
Secondary Treated Group; Subjects who are administered methylene blue for treatment of acquired methemoglobinemia with measured methemoglobin levels ≤ 30 and lack of clinical symptoms	Drug: Methylene Blue; Administration of methylene blue as per the treating physician's diagnosis and the acute care facility's standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of Methemoglobin 1h after Administration of ProvayBlue	Level of methemoglobin 1h after administration of ProvayBlue for treatment of acquired methemoglobinemia compared to pre-treatment level of methemoglobin.	1h post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Normalization of Respiratory Rate	Time to normalization of respiratory rate after administration of ProvayBlue for treatment of acquired methemoglobinemia.	Index Hospitalization
Time to Normalization of Heart Rate	Time to normalization of heart rate after administration of ProvayBlue for treatment of acquired methemoglobinemia.	Index Hospitalization
Prevalence and Nature of Adverse Events	Prevalence and nature of any adverse events occurring within 10 days of the administration of ProvayBlue	Within 10 days of Treatment
Time to Normalization of Blood Pressure	Time to normalization of blood pressure after administration of ProvayBlue for treatment of acquired methemoglobinemia.	Index Hospitalization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence by Agent	Prevalence of acquired methemoglobinemia cases by suspected causal agent	Index Hospitalization
Resolution of Symptoms	Resolution of methemoglobinemia-related symptoms during the index hospitalization	Index Hospitalization

Collaborators and Investigators

• Sponsor: Hospital Quality Foundation
• Collaborators: Prove pharm
• Investigators: Principal Investigator: Charles V Pollack, MD, Hospital Quality Foundation

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: May 20, 2018
• First Submitted That Met QC Criteria: May 20, 2018
• First Posted (Actual): May 31, 2018

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Methylene Blue
• Additional Relevant MeSH Terms: Hematologic Diseases; Methemoglobinemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: HQF-METHB-2018001