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

This study has been completed.
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Gary Cutter, PhD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00294658
First received: February 21, 2006
Last updated: November 17, 2016
Last verified: November 2016
Results First Received: September 19, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Outcomes Assessor);   Primary Purpose: Treatment
Condition: Myasthenia Gravis
Interventions: Procedure: thymectomy plus prednisone
Drug: prednisone alone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first enrollment of two patients started with July 26, 2006 and the last patient was recruited on November 28, 2012. Of the 126 randomized patients, 96 were from centers outside the US and 30 were from US centers.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After informed consent signed, 66 patients were randomized to extended transsternal thymectomy with prednisone treatment and 60 patients were assigned to take prednisone without surgery. Within the 126 subject that started, 15 dropped out before 3 year follow-up.

Reporting Groups
  Description
Thymectomy Plus Prednisone

Procedure: Extended Transsternal Thymectomy plus prednisone treatment

thymectomy: The thymectomy had been performed as soon as possible after randomization.

Prednisone Alone

Drug: prednisone alone protocol

prednisone: Prednisone regimen had been taken every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.


Participant Flow:   Overall Study
    Thymectomy Plus Prednisone   Prednisone Alone
STARTED   66   60 
COMPLETED   60   51 
NOT COMPLETED   6   9 
Death                0                1 
Lost to Follow-up                4                0 
Physician Decision                1                2 
Pregnancy                0                1 
Withdrawal by Subject                0                4 
Found to have invasive thymoma                1                0 
Patient and family were not satisfied                0                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Thymectomy Plus Prednisone

Procedure: Extended Transsternal Thymectomy plus prednisone treatment

thymectomy: The thymectomy will be performed as soon as possible after randomization.

Prednisone Alone

Drug: prednisone alone protocol

prednisone: Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.

Total Total of all reporting groups

Baseline Measures
   Thymectomy Plus Prednisone   Prednisone Alone   Total 
Overall Participants Analyzed 
[Units: Participants]
 66   60   126 
Age 
[Units: Years]
Median (Full Range)
 32 
 (18 to 63) 
 33 
 (18 to 64) 
 32 
 (18 to 64) 
Gender 
[Units: Participants]
Count of Participants
     
Female      50  75.8%      39  65.0%      89  70.6% 
Male      16  24.2%      21  35.0%      37  29.4% 
Race/Ethnicity, Customized 
[Units: Participants]
     
Asian   6   4   10 
Black   7   6   13 
Hispanic   17   17   34 
Non-Hispanic   31   30   61 
Other   5   3   8 
Region of Enrollment 
[Units: Participants]
     
Argentina   10   11   21 
United States   16   14   30 
Japan   1   1   2 
United Kingdom   2   2   4 
Thailand   3   2   5 
Canada   9   9   18 
Netherlands   1   0   1 
Brazil   3   2   5 
Poland   1   1   2 
Italy   6   4   10 
Mexico   1   0   1 
South Africa   4   4   8 
Australia   2   2   4 
Chile   5   5   10 
Germany   2   3   5 
Therapy at enrollment - Pyridostigimine 
[Units: Participants]
     
Yes   60   56   116 
No   5   1   6 
Missing   1   3   4 
Therapy at enrollment - Glucocorticoid 
[Units: Participants]
     
Yes   49   47   96 
No   16   10   26 
Missing   1   3   4 
Previous therapy - Intravenous immue globulin 
[Units: Participants]
     
Yes   12   13   25 
No   53   44   97 
Missing   1   3   4 
Previous therapy - Plasma exchange 
[Units: Participants]
     
Yes   9   7   16 
No   56   50   106 
Missing   1   3   4 
MGFA class [1] 
[Units: Participants]
     
IIa   25   25   50 
IIb   18   14   32 
III   21   20   41 
IV   2   1   3 
[1]

Class IIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.

Class IIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.

Class III. Moderate weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

Class IV. Severe weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.

Higher class was considered worse outcome.

Duration of disease 
[Units: Years]
Median (Full Range)
 1.08 
 (0.02 to 4.41) 
 1.14 
 (0.15 to 4.38) 
 1.11 
 (0.02 to 4.41) 
QMG score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 11.40  (5.12)   12.35  (4.90)   11.84  (5.02) 
[1] Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39, with higher scores indicating more severe disease.
Prednisone use at baseline 
[Units: Participants]
     
Yes   49   47   96 
No   16   10   26 
Missing   1   3   4 
Prednisone Dosage at baseline (mg) [1] 
[Units: Mg]
Mean (Standard Deviation)
 43.43  (28.92)   42.49  (23.52)   42.97  (26.28) 
[1] Prednisone dosage unit as mg, patient has been taken prednisone every other day


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time-weighted Average Quantitative Myasthenia Gravis Weakness Score Over 3 Years   [ Time Frame: baseline, month 3, 4, 6 and every 3 months through 36 months ]

2.  Primary:   Time-weighted Average Alternate-day Prednisone Dose (mg) Measured Over 3 Years   [ Time Frame: baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months ]

3.  Secondary:   Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Prednisone Use at Enrollment   [ Time Frame: baseline, month 3, 4, 6 and every 3 months through 36 months ]

4.  Secondary:   Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Sex   [ Time Frame: baseline, month 3, 4, 6 and every 3 months through 36 months ]

5.  Secondary:   Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Age at Disease Onset   [ Time Frame: baseline, month 3, 4, 6 and every 3 months through 36 months ]

6.  Secondary:   Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Prednisone Use at Enrollment   [ Time Frame: baseline, month 3, 4, 6 and every 3 months through 36 months ]

7.  Secondary:   Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Sex   [ Time Frame: baseline, month 3, 4, 6 and every 3 months through 36 months ]

8.  Secondary:   Subgroup Analyses of Time-weighted Average Average Alternate-day Prednisone Dose (mg) by Age at Disease Onset   [ Time Frame: baseline, month 3, 4, 6 and every 3 months through 36 months ]

9.  Secondary:   Number of Serious Adverse Events   [ Time Frame: baseline to 3 years ]

10.  Secondary:   Number of Patients With at Least One Serious Adverse Events   [ Time Frame: baseline to 3 years ]

11.  Secondary:   Classification of Serious Adverse Events   [ Time Frame: baseline to 3 years ]

12.  Secondary:   Hospitalization for Exacerbation of Myasthenia Gravis   [ Time Frame: baseline to 2 years and baseline to 3 years ]

13.  Secondary:   Cumulative Number of Hospital Days   [ Time Frame: baseline to 3 years ]

14.  Secondary:   Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term   [ Time Frame: baseline to 3 years ]

15.  Secondary:   Time-weighted Average Prescribed Alternate Day Prednisone Dose (mg)   [ Time Frame: baseline-day 20, month 1,2, 3, 4, 6 and every 3 months through 36 months ]

16.  Secondary:   Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 1: Penalized Using Maximum Dose Before Azathioprine)   [ Time Frame: baseline, month 3, 4, 6 and every 3 months through 36 months ]

17.  Secondary:   Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 2: Penalized Using Dose at Time of Starting Azathioprine)   [ Time Frame: baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months ]

18.  Secondary:   Time-Weighted Average MG Activity of Daily Living (MG-ADL)   [ Time Frame: baseline, month 4, 6 and every 3 months through 36 months ]

19.  Secondary:   Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36   [ Time Frame: Month 12, 24, and 36 ]

20.  Secondary:   Azathioprine Use   [ Time Frame: baseline to 3 years ]

21.  Secondary:   Plasma Exchange Use   [ Time Frame: baseline to 3 years ]

22.  Secondary:   Intravenous Immunoglobulin Use   [ Time Frame: baseline to 3 years ]

23.  Secondary:   Minimal Manifestation (MM) Status at Month 12, 24 and 36   [ Time Frame: Month 12, 24 and 36 ]

24.  Secondary:   Cumulative Days in Hospital for Myasthenia Gravis Exacerbation   [ Time Frame: baseline to 2 years ]

25.  Secondary:   Cumulative Days in Hospital for Myasthenia Gravis Exacerbation   [ Time Frame: baseline to 3 years ]

26.  Secondary:   Short Form-36 Standardized Physical Component   [ Time Frame: Month 0, Month 12, Month 24 and Month 36 ]

27.  Secondary:   Short Form-36 Standardized Mental Component   [ Time Frame: Month 0, Month 12, Month 24 and Month 36 ]

28.  Secondary:   Treatment Associated Complications (TAC)   [ Time Frame: Month 0, 1, 2, 3, 4 then every 3 months through Month 36 ]

29.  Secondary:   Treatment Associated Symptoms (TAS)   [ Time Frame: Month 0, 1, 2, 3, 4 then every 3 months through Month 36 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Potential weakness of this trial include the single-blinded and pill count methodology.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Gary Cutter, Professor
Organization: University of Alabama at Birmingham
phone: 205-975-5048
e-mail: cutter@uab.edu


Publications of Results:


Responsible Party: Gary Cutter, PhD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00294658     History of Changes
Other Study ID Numbers: R01NS050733
1U01NS042685-01A2 ( US NIH Grant/Contract Award Number )
CRC ( Other Identifier: NINDS )
Study First Received: February 21, 2006
Results First Received: September 19, 2016
Last Updated: November 17, 2016
Health Authority: United States: Federal Government