Disease-Modifying Treatments for Myasthenia Gravis (PROMISE-MG)

February 2, 2021 updated by: Duke University

Prospective Multicenter Observational Cohort Study of Comparative Effectiveness of Disease-modifying Treatments for Myasthenia Gravis

This study is designed to address the evidence gaps in a real-world setting and help patients with MG choose treatments that are best suited to them. It is a prospective, multicenter observational cohort study of comparative effectiveness of MG treatments, with a patient-centered primary outcome measure, to guide clinicians, patients and payers regarding the choice of treatment options for this chronic and serious disease.

Primary: To compare the effectiveness of azathioprine (AZT) and mycophenolate mofetil (MMF).

Secondary: To compare the outcomes in patients receiving an adequate dose and duration of AZT or MMF over the 2-3 year study period, vs. patients not receiving adequate doses and duration of these agents

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Design & procedures - This is an observational study in the real world clinical setting to evaluate immunosuppressive treatment (IS) of myasthenia gravis (MG). Patients with acquired autoimmune MG ≥ 18 years of age who are not on IS agents, and have not been on corticosteroids for at least 30 days will be enrolled at 20 sites in the US and Canada. These patients will be treated according to the physician's judgment and patient preferences as in routine clinical practice. Patients will be followed prospectively, with the frequency of clinical visits and laboratory monitoring determined by the treating physician, which may differ among patients. Standard outcome measures measuring efficacy and adverse effects that are used in clinical practice will be collected, with emphasis on patient reported outcomes. Informed consent will be obtained using an approved consent form. Patient identifiable / clinical information from the medical record, including the study outcome measures will be uploaded to a centralized REDCap database. The investigators plan to recruit 220 patients, adjusting for a 10% drop out rate, with a final sample of 200 patients for analysis.

Study Type

Observational

Enrollment (Actual)

167

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G2G3
        • University of Alberta Hospital, Faculty of Medicine
    • Ontario
      • London, Ontario, Canada, N6A5A5
        • London Health Sciences Centre
  • United States
    • California
      • Palo Alto, California, United States, 84303
        • Stanford University
    • Florida
      • Miami, Florida, United States, 33136
        • Unversity of Miami
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Brighton, Massachusetts, United States, 02135
        • St. Elizabeth's Medical Center
    • New York
      • Buffalo, New York, United States, 14202
        • University at Buffalo, SUNY
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont - Larner College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

MG patients with autoimmune MG

Description

Inclusion Criteria:

Participants eligible for inclusion in this study must fulfill all of the following criteria:

  1. Age ≥ 18 years of age

  2. Acquired autoimmune MG, with weakness and confirmed by one or more of the following:

    1. Elevated AChR or MuSK antibodies
    2. Unequivocal response to cholinesterase inhibitors
    3. Abnormal RNS or increased jitter (without nerve or muscle disease sufficient to produce a decrement or increased jitter)
  3. Patients seen initially at the participating center after January 1, 2017.
  4. Patients on pyridostigmine at the first evaluation at the participating center ("baseline visit") may be included if pyridostigmine was started ≤3 months before the baseline visit.
  5. Patients who received corticosteroids >90 days prior to baseline visit for a non-MG indication may be included. (Patients who have received corticosteroids for a non-MG indication between 31 and 90 days before baseline visit will be evaluated by the primary investigators on a case by case basis to determine if the extent and dose of corticosteroid could have impacted the course of MG or symptoms of MG.)

Exclusion Criteria:

Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible participants.

  1. Patients with non-autoimmune MG (congenital myasthenic syndromes, drug-induced MG)
  2. Patients on immunosuppressive agents at the baseline visit.
  3. Patients who have previously received steroids for the treatment of MG.
  4. Patients with steroid use for a non-MG indication < 30 days prior to the baseline visit.
  5. Patients with previous thymectomy, IVIg or plasma exchange, or treatment with a non-steroidal immunosuppressive agent (azathioprine, mycophenolate mofetil cyclosporine, methotrexate, cyclophosphamide, tacrolimus, rituximab, or any investigational immunosuppressive agent). Patients who have outcomes measured within 24 hours after initiation of IVIg or PLEX are acceptable.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
azathioprine (AZT)
Patients with MG who are receiving azathioprine as part of routine clinical care
Drug: Azathioprine
oral tablet
Other Names:
  • Imuran
mycophenolate mofetil (MMF)
Patients with MG who are receiving mycophenolate mofetil as part of routine clinical care
Drug: Mycophenolate Mofetil
oral tablets
Other Names:
  • Cellcept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Patient-Reported Myasthenia Gravis Quality of Life, 15, revised ( MG-QOL15r)
Time Frame: Baseline, 24-36 months
Measures MG symptoms, physical, social and emotional functioning related to MG, with 15 items, 3 response option, 0-2 for each item, Total score range 0-30, higher scores indicating worse function
Baseline, 24-36 months
Change in composite outcome of clinical improvement and adverse effects
Time Frame: Baseline, 24-36 months

measured by a composite of clinical improvement and adverse effects of treatments. Clinical improvement: achievement of MGFA Post-Intervention Status (PIS) Minimal Manifestation Status (MM) or better, defined below.

Adverse effects end point: no more than Grade 1 CTCAE (Common Terminology Criteria for Adverse Events) medication side-effects, defined below.

MGFA PIS- MM: the patient has no symptoms or functional limitations from MG but has some weakness on examination of some muscles

CTCAE: list of adverse event (AE) terms commonly encountered in oncology but is useful to monitor the side effects of any intervention Each AE term is defined and graded on a 1 to 5 scale indicating the severity of the AE, 1 representing the mildest side effect and 5 representing death Grade 1 CTCAE side-effects: "asymptomatic or only mild symptoms; intervention not indicated"
Baseline, 24-36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Myasthenia gravis composite (MGC) scores
Time Frame: Baseline, 24-36 months

10 item scale of patient-reported functions and clinician-reported examination findings.

Scores range from 0-50 (0- normal and 50- most severe)
Baseline, 24-36 months
Change in Myasthenia Gravis Activities of Daily Living Scale (MG-ADL)
Time Frame: Baseline, 24-36 months
Patient-reported 8- item questionnaire evaluating commonly reported symptoms in MG on a 4 response scale from 0-3 (0 - normal, 3- highest disability) Range 0-24, higher score is worse
Baseline, 24-36 months
Change in Myasthenia Gravis Manual Muscle Test scores (MG-MMT)
Time Frame: Baseline, 24-36 months
Clinician-assessed scale of 18 muscle functions commonly affected by MG, each graded from 0 (normal) to 4 (paralyzed/unable to perform), Range 0-120, higher score reflects worse function
Baseline, 24-36 months
Change in Visual Analogue Scale (VAS) for Disease Severity
Time Frame: Baseline, 24-36 months
Patient perception of disease severity measured in millimeters on a 100 mm line. Higher number indicates more severe disease
Baseline, 24-36 months
Change in Visual Analogue Scale (VAS) for Treatment Side effects
Time Frame: Baseline, 24-36 months
patient perception of side effects of treatment measured in millimeters on a 100 mm line. Higher number indicates worse side effects
Baseline, 24-36 months
Change in number of hospitalizations for MG
Time Frame: Baseline, 24-36 months
counts of hospitalizations for MG- higher count is worse
Baseline, 24-36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Patient-Centered Outcomes Research Institute
Beth Israel Deaconess Medical Center

Investigators

  • Principal Investigator: Jeffery Guptill, MD, Duke University
  • Principal Investigator: Donald Sanders, MD, Duke University
  • Principal Investigator: Pushpa Narayanaswami, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2018

Primary Completion (Actual)

January 31, 2021

Study Completion (Actual)

January 31, 2021

Study Registration Dates

First Submitted

March 21, 2018

First Submitted That Met QC Criteria

April 5, 2018

First Posted (Actual)

April 6, 2018

Study Record Updates

Last Update Posted (Actual)

February 3, 2021

Last Update Submitted That Met QC Criteria

February 2, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00087883

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

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Autoimmune Diseases

Clinical Trials on Azathioprine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Pakistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe