Intravenous Immunoglobulin and Plasma Exchange in Myasthenia Gravis

This study has been completed.
Sponsor:
Collaborator:
Grifols Therapeutics Inc.
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01179893
First received: August 9, 2010
Last updated: NA
Last verified: August 2010
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Myasthenia Gravid
Biological: IVIG
Procedure: PLEX
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Trial of Plasma Exchange vs. IVIG in the Treatment of Myasthenia Gravis

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Change in QMGS with time to see if effect ad day 14 is sustained.

  • Post intervention status [ Time Frame: Day 14, 21 and 28 ] [ Designated as safety issue: No ]
    Categorical scale of improvement, worsening, or no change for myasthenia gravis.

  • Single fiber electromyography: jitter, percent abnormal pair, percent blocking [ Time Frame: Days 14 and 28 compared to baseline ] [ Designated as safety issue: No ]
    Electrophysiological assessment of neuromuscular transmission.

  • Repetitive Nerve stimulation studies [ Time Frame: Days 14 and 28 ] [ Designated as safety issue: No ]
    Assessment of decrement

  • Acetylcholine Receptor Antibody titers [ Time Frame: Day 28 (if positive at baseline) ] [ Designated as safety issue: No ]
    Laboratory assay of pathogenic antibody

  • AntiMUSK antibody [ Time Frame: Day 28 (if positive at baseline) ] [ Designated as safety issue: No ]
    Laboratory measure of pathogenic antibody

  • Need for ICU admission, ventilation, intubation [ Time Frame: 60 days ] [ Designated as safety issue: Yes ]
    Myasthenic deterioration and crisis

  • Hospitalization [ Time Frame: 60 days ] [ Designated as safety issue: Yes ]
    Myasthenic deterioration and crisis

  • Need for additional myasthenic treatment [ Time Frame: Day 60 ] [ Designated as safety issue: Yes ]
    Myasthenic deterioration or crisis


Enrollment: 87
Study Start Date: March 2007
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01179893

Locations
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
Grifols Therapeutics Inc.
Investigators
Principal Investigator: Vera Bril, BSc, MD, FRCPC University Health Network, Toronto
Principal Investigator: David Barth, MD University Heatlh Network
  More Information

Publications:
Responsible Party: Vera Bril, University Health Network
ClinicalTrials.gov Identifier: NCT01179893     History of Changes
Other Study ID Numbers: 07-0280-B
Study First Received: August 9, 2010
Last Updated: August 9, 2010
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Myasthenia Gravis
IVIG
PLEX

Additional relevant MeSH terms:
Myasthenia Gravis
Muscle Weakness
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014