Intravenous Immunoglobulin and Plasma Exchange in Myasthenia Gravis

August 9, 2010 updated by: University Health Network, Toronto

A Randomized Trial of Plasma Exchange vs. IVIG in the Treatment of Myasthenia Gravis

Immunomodulation is effective in treating patients with myasthenia gravis (MG), but prior studies have not adequately defined if plasma exchange (PLEX) in superior to intravenous immunoglobulin (IVIG) in the treatment of myasthenia gravis. This study aimed to determine if PLEX was superior to IVIG in the treatment of patients with myasthenia gravis.

Patients with MG requiring immunomodulation are randomized to IVIG or PLEX and treated with a full course of immunomodulation. The quantitative myasthenia gravis score (QMGS) will be evaluated as the primary efficacy parameter at day 14 to determine if PLEX is superior to IVIG.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

87

Phase

  • Phase 4

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
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • University Health Network

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

Description

Inclusion Criteria:

  • >18 years old
  • diagnosis of moderate-severe MG (defined as a Quantitative Myasthenia Gravis Score QMGS >10.5)
  • worsening weakness requiring a change in therapy judged by a neuromuscular expert

Exclusion Criteria:

  • Worsening weakness secondary to concurrent medications (e.g. Aminoglycosides)
  • Worsening weakness secondary to infection
  • Change in corticosteroid dosage in the 2 weeks prior to screening
  • Other disorders causing weakness or fatigue
  • Known absolute IgA deficiency (risk of anaphylactic reaction to IVIG)
  • History of anaphylaxis or severe systemic response to IVIG or albumin
  • Pregnancy or breastfeeding
  • Active renal failure precluding volume of IVIG (risk of volume overload with IVIG) as judged by the investigators
  • Clinically significant cardiac disease precluding IVIG volume as judged by the investigators
  • Known hyperviscosity or hypercoaguable state (risk of stroke with IVIG)
  • Known coagulopathy with bleeding
  • On another current study medication or protocol within 4 weeks of screening
  • Patients with known refractory status to either IVIG or PLEX
  • Poorly controlled or severe hypertension (exacerbation by IVIG)
  • Patient refuses treatment with either IVIG or PLEX
  • Patient refuses follow-up with electrophysiological studies
  • Patient unable or unwilling to give informed consent

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: IVIG
Intravenous Immunoglobulin, 2G/Kg, infused over 2 days in the Medical Day Unit of the University Health Network
Biological: IVIG
Intravenous immunoglobulin
Experimental: PLEX
Patients received one plasma volume plasma exchanges with 5% albumin replacement fluid. Five plasma exchange procedures occurred every second day with breaks over the weekend allowed. Patients treated in the apheresis units at the University Health Network.
Procedure: PLEX
Plasma exchange: removal of pathogenic antibodies and constituents and replacement with albumin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 14 after treatment
Time Frame: QMGS at day 14, and patients followed to day 60
QMGS is a validated clinical measure of myasthenia gravis ranging from 0 points (no myasthenic weakness) to a maximum of 39 points, with a defined change of 3.4 units required for clinical significance.
QMGS at day 14, and patients followed to day 60

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
QMGS Score change at days 21 and 28 from start of treatment.
Time Frame: 28 days
Change in QMGS with time to see if effect ad day 14 is sustained.
28 days
Post intervention status
Time Frame: Day 14, 21 and 28
Categorical scale of improvement, worsening, or no change for myasthenia gravis.
Day 14, 21 and 28
Single fiber electromyography: jitter, percent abnormal pair, percent blocking
Time Frame: Days 14 and 28 compared to baseline
Electrophysiological assessment of neuromuscular transmission.
Days 14 and 28 compared to baseline
Repetitive Nerve stimulation studies
Time Frame: Days 14 and 28
Assessment of decrement
Days 14 and 28
Acetylcholine Receptor Antibody titers
Time Frame: Day 28 (if positive at baseline)
Laboratory assay of pathogenic antibody
Day 28 (if positive at baseline)
AntiMUSK antibody
Time Frame: Day 28 (if positive at baseline)
Laboratory measure of pathogenic antibody
Day 28 (if positive at baseline)
Need for ICU admission, ventilation, intubation
Time Frame: 60 days
Myasthenic deterioration and crisis
60 days
Hospitalization
Time Frame: 60 days
Myasthenic deterioration and crisis
60 days
Need for additional myasthenic treatment
Time Frame: Day 60
Myasthenic deterioration or crisis
Day 60

Collaborators and Investigators

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

Sponsor

University Health Network, Toronto

Collaborators

Grifols Therapeutics LLC

Investigators

  • Principal Investigator: Vera Bril, BSc, MD, FRCPC, University Health Network, Toronto
  • Principal Investigator: David Barth, MD, University Heatlh Network

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

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

March 1, 2007

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

August 9, 2010

First Submitted That Met QC Criteria

August 9, 2010

First Posted (Estimate)

August 11, 2010

Study Record Updates

Last Update Posted (Estimate)

August 11, 2010

Last Update Submitted That Met QC Criteria

August 9, 2010

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-0280-B

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.

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