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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00294658
Ethics application status
Date submitted
21/02/2006
Date registered
22/02/2006

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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents



Results are available at https://clinicaltrials.gov/study/NCT00294658