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Intravenous Immunoglobulin and Plasma Exchange in Myasthenia Gravis

Primary Purpose

Myasthenia Gravid

Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
IVIG
PLEX
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myasthenia Gravid focused on measuring Myasthenia Gravis, IVIG, PLEX

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Health Network

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

IVIG

PLEX

Arm Description

Intravenous Immunoglobulin, 2G/Kg, infused over 2 days in the Medical Day Unit of the University Health Network

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.

Outcomes

Primary Outcome Measures

Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 14 after treatment
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.

Secondary Outcome Measures

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

Full Information

First Posted
August 9, 2010
Last Updated
August 9, 2010
Sponsor
University Health Network, Toronto
Collaborators
Grifols Therapeutics LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01179893
Brief Title
Intravenous Immunoglobulin and Plasma Exchange in Myasthenia Gravis
Official Title
A Randomized Trial of Plasma Exchange vs. IVIG in the Treatment of Myasthenia Gravis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2010
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University Health Network, Toronto
Collaborators
Grifols Therapeutics LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myasthenia Gravid
Keywords
Myasthenia Gravis, IVIG, PLEX

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IVIG
Arm Type
Active Comparator
Arm Description
Intravenous Immunoglobulin, 2G/Kg, infused over 2 days in the Medical Day Unit of the University Health Network
Arm Title
PLEX
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
IVIG
Intervention Description
Intravenous immunoglobulin
Intervention Type
Procedure
Intervention Name(s)
PLEX
Intervention Description
Plasma exchange: removal of pathogenic antibodies and constituents and replacement with albumin.
Primary Outcome Measure Information:
Title
Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 14 after treatment
Description
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.
Time Frame
QMGS at day 14, and patients followed to day 60
Secondary Outcome Measure Information:
Title
QMGS Score change at days 21 and 28 from start of treatment.
Description
Change in QMGS with time to see if effect ad day 14 is sustained.
Time Frame
28 days
Title
Post intervention status
Description
Categorical scale of improvement, worsening, or no change for myasthenia gravis.
Time Frame
Day 14, 21 and 28
Title
Single fiber electromyography: jitter, percent abnormal pair, percent blocking
Description
Electrophysiological assessment of neuromuscular transmission.
Time Frame
Days 14 and 28 compared to baseline
Title
Repetitive Nerve stimulation studies
Description
Assessment of decrement
Time Frame
Days 14 and 28
Title
Acetylcholine Receptor Antibody titers
Description
Laboratory assay of pathogenic antibody
Time Frame
Day 28 (if positive at baseline)
Title
AntiMUSK antibody
Description
Laboratory measure of pathogenic antibody
Time Frame
Day 28 (if positive at baseline)
Title
Need for ICU admission, ventilation, intubation
Description
Myasthenic deterioration and crisis
Time Frame
60 days
Title
Hospitalization
Description
Myasthenic deterioration and crisis
Time Frame
60 days
Title
Need for additional myasthenic treatment
Description
Myasthenic deterioration or crisis
Time Frame
Day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vera Bril, BSc, MD, FRCPC
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Barth, MD
Organizational Affiliation
University Heatlh Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
17353471
Citation
Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial. Neurology. 2007 Mar 13;68(11):837-41. doi: 10.1212/01.wnl.0000256698.69121.45.
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Intravenous Immunoglobulin and Plasma Exchange in Myasthenia Gravis

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