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Phase 3 N=126 Randomized Single-blind Treatment

Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy

Myasthenia Gravis

Enrolled (actual)
126
Serious AEs
46.0%
Results posted
Jan 2017
Primary outcome: Primary: Time-weighted Average Quantitative Myasthenia Gravis Weakness Score Over 3 Years — 6.15; 8.99 units on a scale

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
thymectomy plus prednisone (Procedure); prednisone alone (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
University of Alabama at Birmingham
Primary completion
Nov 2015

Outcome Measures

OutcomeResultp-value
PRIMARY
Time-weighted Average Quantitative Myasthenia Gravis Weakness Score Over 3 Years
6.15; 8.99
PRIMARY
Time-weighted Average Alternate-day Prednisone Dose (mg) Measured Over 3 Years
32; 54
SECONDARY
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Prednisone Use at Enrollment
6.30; 9.10; 5.66; 8.84
SECONDARY
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Sex
6.47; 9.73; 5.23; 7.45
SECONDARY
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Age at Disease Onset
6.50; 9.60; 5.33; 7.85
SECONDARY
Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Prednisone Use at Enrollment
35; 56; 25; 45
SECONDARY
Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Sex
33; 54; 31; 55
SECONDARY
Subgroup Analyses of Time-weighted Average Average Alternate-day Prednisone Dose (mg) by Age at Disease Onset
35; 55; 27; 49
SECONDARY
Number of Serious Adverse Events
48; 93
SECONDARY
Number of Patients With at Least One Serious Adverse Events
25; 33
SECONDARY
Classification of Serious Adverse Events
1; 7; 8; 2; 9; 5
SECONDARY
Hospitalization for Exacerbation of Myasthenia Gravis
6; 17; 6; 22
SECONDARY
Cumulative Number of Hospital Days
8.4; 19.2
SECONDARY
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term
2; 2; 0; 1; 4; 7
SECONDARY
Time-weighted Average Prescribed Alternate Day Prednisone Dose (mg)
34.3; 55.6
SECONDARY
Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 1: Penalized Using Maximum Dose Before Azathioprine)
34.4; 64.4
SECONDARY
Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 2: Penalized Using Dose at Time of Starting Azathioprine)
33.3; 57.9
SECONDARY
Time-Weighted Average MG Activity of Daily Living (MG-ADL)
2.24; 3.41
SECONDARY
Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36
1.92; 3.33; 2.02; 3.11; 2.14; 2.69
SECONDARY
Azathioprine Use
11; 28
SECONDARY
Plasma Exchange Use
10; 9
SECONDARY
Intravenous Immunoglobulin Use
11; 23
SECONDARY
Minimal Manifestation (MM) Status at Month 12, 24 and 36
41; 20; 39; 20; 39; 24
SECONDARY
Cumulative Days in Hospital for Myasthenia Gravis Exacerbation
8.7; 22.5
SECONDARY
Cumulative Days in Hospital for Myasthenia Gravis Exacerbation
8.7; 22.5
SECONDARY
Short Form-36 Standardized Physical Component
41.4; 37.9; 48.4; 44.4; 50.3; 43.0
SECONDARY
Short Form-36 Standardized Mental Component
49.1; 46.2; 39.1; 41.7; 49.9; 46.7
SECONDARY
Treatment Associated Complications (TAC)
22; 17; 15; 15; 22; 20
SECONDARY
Treatment Associated Symptoms (TAS)
63; 53; 55; 52; 61; 53

Summary

The purpose of this trial is to determine if thymectomy combined with prednisone therapy is more beneficial in treating non-thymomatous myasthenia gravis than prednisone therapy alone.

Eligibility Criteria

Inclusion Criteria

  • Male and female MG patients age greater than 18 and less than 65 years
  • Onset of generalized MG within the last 5 years
  • Positive serum anti-acetylcholine receptor binding antibodies (muscle acetylcholine receptors, AchRAb =/> 1.00 nmol/L. AchRAb levels of 0.50-0.99 nmol/L will be acceptable if there is another confirmatory test for MG, including single-fiber electromyography (EMG), repetitive nerve stimulation, or unequivocal edrophonium testing.)
  • MGFA class II-IV at entry, using the MG Foundation of America (MGFA) classification, while receiving optimal anti-cholinesterase treatment with or without oral prednisone

Exclusion Criteria

  • Ocular MG without generalized weakness (MGFA Class I) or minimal weakness that would not require the use of corticosteroids
  • Myasthenic weakness requiring intubation (MGFA Class IV) in the prior month
  • Immunosuppressive therapy other than corticosteroids in the preceding year
  • Medically unfit for thymectomy
  • Chest CT evidence of thymoma.
  • Pregnancy or lactation; contraindications to the use of corticosteroids, unless postmenopausal or surgically sterile. Women considering becoming pregnant during the period of the study are to be excluded.
  • A serious concurrent medical, neurological or psychiatric condition that would interfere with thymectomy or subsequent clinical assessments
  • Current alternate day dose of prednisone > than 1.5 mg/kg or 100 mg or the equivalent daily doses (> 0.75 mg/kg or 50 mg).
  • Participation in another experimental clinical trial
  • History of alcohol or drug abuse within the 2 years prior to randomization.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00294658). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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