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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00294658




Registration number
NCT00294658
Ethics application status
Date submitted
21/02/2006
Date registered
22/02/2006
Date last updated
23/05/2017

Titles & IDs
Public title
Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy
Scientific title
A Multi-Center, Single-Blind, Randomized Study Comparing Thymectomy to No Thymectomy in Non-Thymomatous Myasthenia Gravis (MG) Patients Receiving Prednisone
Secondary ID [1] 0 0
1U01NS042685-01A2
Secondary ID [2] 0 0
R01NS050733
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myasthenia Gravis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Neurological 0 0 0 0
Other neurological disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - thymectomy plus prednisone
Treatment: Drugs - prednisone alone

Active Comparator: Thymectomy plus prednisone - Procedure: Extended Transsternal Thymectomy plus prednisone treatment

Placebo Comparator: Prednisone alone - Drug: prednisone alone protocol


Treatment: Surgery: thymectomy plus prednisone
The thymectomy will be performed as soon as possible after randomization.

Treatment: Drugs: prednisone alone
Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time-weighted Average Quantitative Myasthenia Gravis Weakness Score Over 3 Years
Timepoint [1] 0 0
baseline, month 3, 4, 6 and every 3 months through 36 months
Primary outcome [2] 0 0
Time-weighted Average Alternate-day Prednisone Dose (mg) Measured Over 3 Years
Timepoint [2] 0 0
baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months
Secondary outcome [1] 0 0
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Prednisone Use at Enrollment
Timepoint [1] 0 0
baseline, month 3, 4, 6 and every 3 months through 36 months
Secondary outcome [2] 0 0
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Sex
Timepoint [2] 0 0
baseline, month 3, 4, 6 and every 3 months through 36 months
Secondary outcome [3] 0 0
Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Age at Disease Onset
Timepoint [3] 0 0
baseline, month 3, 4, 6 and every 3 months through 36 months
Secondary outcome [4] 0 0
Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Prednisone Use at Enrollment
Timepoint [4] 0 0
baseline, month 3, 4, 6 and every 3 months through 36 months
Secondary outcome [5] 0 0
Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Sex
Timepoint [5] 0 0
baseline, month 3, 4, 6 and every 3 months through 36 months
Secondary outcome [6] 0 0
Subgroup Analyses of Time-weighted Average Average Alternate-day Prednisone Dose (mg) by Age at Disease Onset
Timepoint [6] 0 0
baseline, month 3, 4, 6 and every 3 months through 36 months
Secondary outcome [7] 0 0
Number of Serious Adverse Events
Timepoint [7] 0 0
baseline to 3 years
Secondary outcome [8] 0 0
Number of Patients With at Least One Serious Adverse Events
Timepoint [8] 0 0
baseline to 3 years
Secondary outcome [9] 0 0
Classification of Serious Adverse Events
Timepoint [9] 0 0
baseline to 3 years
Secondary outcome [10] 0 0
Hospitalization for Exacerbation of Myasthenia Gravis
Timepoint [10] 0 0
baseline to 2 years and baseline to 3 years
Secondary outcome [11] 0 0
Cumulative Number of Hospital Days
Timepoint [11] 0 0
baseline to 3 years
Secondary outcome [12] 0 0
Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term
Timepoint [12] 0 0
baseline to 3 years
Secondary outcome [13] 0 0
Time-weighted Average Prescribed Alternate Day Prednisone Dose (mg)
Timepoint [13] 0 0
baseline-day 20, month 1,2, 3, 4, 6 and every 3 months through 36 months
Secondary outcome [14] 0 0
Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 1: Penalized Using Maximum Dose Before Azathioprine)
Timepoint [14] 0 0
baseline, month 3, 4, 6 and every 3 months through 36 months
Secondary outcome [15] 0 0
Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 2: Penalized Using Dose at Time of Starting Azathioprine)
Timepoint [15] 0 0
baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months
Secondary outcome [16] 0 0
Time-Weighted Average MG Activity of Daily Living (MG-ADL)
Timepoint [16] 0 0
baseline, month 4, 6 and every 3 months through 36 months
Secondary outcome [17] 0 0
Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36
Timepoint [17] 0 0
Month 12, 24, and 36
Secondary outcome [18] 0 0
Azathioprine Use
Timepoint [18] 0 0
baseline to 3 years
Secondary outcome [19] 0 0
Plasma Exchange Use
Timepoint [19] 0 0
baseline to 3 years
Secondary outcome [20] 0 0
Intravenous Immunoglobulin Use
Timepoint [20] 0 0
baseline to 3 years
Secondary outcome [21] 0 0
Minimal Manifestation (MM) Status at Month 12, 24 and 36
Timepoint [21] 0 0
Month 12, 24 and 36
Secondary outcome [22] 0 0
Cumulative Days in Hospital for Myasthenia Gravis Exacerbation
Timepoint [22] 0 0
baseline to 2 years
Secondary outcome [23] 0 0
Cumulative Days in Hospital for Myasthenia Gravis Exacerbation
Timepoint [23] 0 0
baseline to 3 years
Secondary outcome [24] 0 0
Short Form-36 Standardized Physical Component
Timepoint [24] 0 0
Month 0, Month 12, Month 24 and Month 36
Secondary outcome [25] 0 0
Short Form-36 Standardized Mental Component
Timepoint [25] 0 0
Month 0, Month 12, Month 24 and Month 36
Secondary outcome [26] 0 0
Treatment Associated Complications (TAC)
Timepoint [26] 0 0
Month 0, 1, 2, 3, 4 then every 3 months through Month 36
Secondary outcome [27] 0 0
Treatment Associated Symptoms (TAS)
Timepoint [27] 0 0
Month 0, 1, 2, 3, 4 then every 3 months through Month 36

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2015
Sample size
Target
Accrual to date
Final
126
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
University of Sydney, Royal Prince Alfred Hospital and The University of Sydney - Sydney
Recruitment hospital [2] 0 0
University of Melbourne, Melbourne, The Royal Melbourne Hospital, Dept of Neurology, Royal Melbourne Hospital - Victoria
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
3050 - Victoria
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Vermont
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
United States of America
State/province [20] 0 0
West Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Argentina
State/province [22] 0 0
Buenos Aires
Country [23] 0 0
Brazil
State/province [23] 0 0
Brasilia
Country [24] 0 0
Brazil
State/province [24] 0 0
Curitiba
Country [25] 0 0
Brazil
State/province [25] 0 0
Rio De Janeiro
Country [26] 0 0
Canada
State/province [26] 0 0
Alberta
Country [27] 0 0
Canada
State/province [27] 0 0
British Columbia
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
Chile
State/province [30] 0 0
Santiago
Country [31] 0 0
Germany
State/province [31] 0 0
Baden-Württemberg
Country [32] 0 0
Germany
State/province [32] 0 0
Bavaria
Country [33] 0 0
Germany
State/province [33] 0 0
North Rhine-Westphalia
Country [34] 0 0
Germany
State/province [34] 0 0
Rhineland-Palatinate
Country [35] 0 0
Germany
State/province [35] 0 0
Münster
Country [36] 0 0
Germany
State/province [36] 0 0
Tübingen
Country [37] 0 0
Italy
State/province [37] 0 0
Milan
Country [38] 0 0
Italy
State/province [38] 0 0
Rome
Country [39] 0 0
Italy
State/province [39] 0 0
Torino
Country [40] 0 0
Japan
State/province [40] 0 0
Ishikawa
Country [41] 0 0
Japan
State/province [41] 0 0
Kyushu
Country [42] 0 0
Mexico
State/province [42] 0 0
Mexico
Country [43] 0 0
Netherlands
State/province [43] 0 0
Leiden
Country [44] 0 0
Poland
State/province [44] 0 0
Województwo
Country [45] 0 0
Portugal
State/province [45] 0 0
Porto
Country [46] 0 0
South Africa
State/province [46] 0 0
Cape Town
Country [47] 0 0
Spain
State/province [47] 0 0
Barcelona
Country [48] 0 0
Taiwan
State/province [48] 0 0
New Taipei
Country [49] 0 0
Thailand
State/province [49] 0 0
Bangkok
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Glasgow
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Liverpool
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Manchester
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Oxford
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Other
Name
University of Alabama at Birmingham
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Neurological Disorders and Stroke (NINDS)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00294658
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gary Cutter, PhD
Address 0 0
University of Alabama at Birmingham School of Public Health, Department of Biostatistics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries