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Completed

NCT Number: NCT00294658

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

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.

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Key information

Conditions

Myasthenia Gravis Autoimmune Diseases Autoimmune Diseases of the Nervous System Hemic and Lymphatic Diseases Immune System Diseases Lymphatic Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Complex and Mixed Nervous System Diseases Nervous System Neoplasms Neurodegenerative Diseases Neuromuscular Diseases Neuromuscular Junction Diseases Paraneoplastic Syndromes Paraneoplastic Syndromes, Nervous System Thoracic Neoplasms Thymoma Thymus Neoplasms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Buenis, Centro de Asistencia Docencia e Investigacion en Miastenia (CADIMI) Av. Forest 1146 - Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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About this study

Myasthenia gravis (MG) is an autoimmune disease involving the thymus in which 85 percent of patients have antibodies to muscle acetylcholine receptors (AchR-Ab) that interfere with neuromuscular transmission. MG frequently causes severe disability that can be life-threatening. Thymectomy-a surgical procedure that removes thymus gland tissue from the chest cavity-has been an established therapy for non-thymomatous MG, or MG without thymoma, for more than 60 years (based on retrospective, non-randomized studies). Corticosteroids are now being used increasingly either as the sole treatment or in combination with thymectomy. Both therapies have associated adverse effects and indications for their use based on randomized trial data are lacking.

The purpose of this 5-year trial is to determine if the surgical procedure, extended transsternal thymectomy (ETTX), combined with prednisone therapy is more beneficial in treating individuals with non-thymomatous MG than prednisone therapy alone. More specifically, this study will determine 1) if ETTX combined with prednisone results in a greater improvement in myasthenic weakness, compared to prednisone alone; 2) if ETTX combined with prednisone results in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long-term toxic effects, compared to prednisone alone; and 3) if ETTX combined with prednisone enhances quality of life by reducing adverse events and symptoms associated with the therapies, compared to prednisone alone.

Learning that thymectomy results in a meaningful reduction of prednisone dosage or even full withdrawal or reduces side effects related to prednisone would support using the two treatments-thymectomy and prednisone-together. However, if no meaningful reduction of prednisone dosage or side effects is shown, the results would mean that using the two treatments together offers no advantages over prednisone treatment alone.

After an initial screening, study participants will be randomized either to undergo the surgical procedure ETTX and receive prednisone treatment, or to receive prednisone treatment alone without surgery. Participants will be followed for at least 3 years.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

thymectomy plus prednisone

Procedure

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

Other names: Extended transsternal thymectomy plus prednisone

prednisone alone

Drug

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

Other names: prednisolone

Primary outcomes

  1. 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

    Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease. The time weighted average is a calculation that provides an integrated measure of the outcome over the time of followup. The denominator that was used to compute the time-weighted average for the Quantitative Myasthenia Gravis (QMG) score and the prednisone dose was the number of days from randomization to the last visit. Computations used the trapezoidal method where in the QMG score is multiplied by the number of days at this level from one visit to the next and added up over the entire followup experience and divided by the total number of days from randomization.

  2. 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

    Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.

Secondary outcomes

  1. 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

    Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.

  2. 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

    Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.

  3. 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

    Myasthenia Gravis (QMG) test. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease.

  4. 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

    Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.

  5. 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

    Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.

  6. 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

    Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prednisone dosages had been weighted over the days of reporting period.

  7. Number of Serious Adverse Events

    Time frame: baseline to 3 years

    Number of participant who experienced at least one serious adverse events over 3 years: Thymectomy plus prednisone n=25 (out of 66); Prednisone alone n=33 (out of 60)

  8. Number of Patients With at Least One Serious Adverse Events

    Time frame: baseline to 3 years

    Number of participant who experienced at least one serious adverse events over 3 years: Thymectomy plus prednisone n=25 (out of 66); Prednisone alone n=33 (out of 60)

  9. Classification of Serious Adverse Events

    Time frame: baseline to 3 years

  10. Hospitalization for Exacerbation of Myasthenia Gravis

    Time frame: baseline to 2 years and baseline to 3 years

  11. Cumulative Number of Hospital Days

    Time frame: baseline to 3 years

    Number who had hospitalization: Thymectomy plus prednisone n=15 (out of 66); Prednisone alone n=31 (out of 60)

  12. Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term

    Time frame: baseline to 3 years

    Number who had hospitalization: Thymectomy plus prednisone n=15 (out of 66); Prednisone alone n=31 (out of 60)

  13. 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

    Physicians reported prescribed alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up. The prescribed prednisone dosages had been weighted over the days of reporting period.

  14. 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

    For each participant who took azathioprine, we penalized them by taking the maximum dose of prednisone before azathioprine was added. We then applied the same method to compute the time-weighted alternative day prednisone dose from baseline, month 3, 4, 6 and every 3 months through 36 months.

  15. 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

    For each participant who took azathioprine, we penalized them by taking the prednisone dose at the time azathioprine commenced. We then applied the same method to compute the time-weighted alternative day prednisone dose from baseline, month 3, 4, 6 and every 3 months through 36 months.

  16. Time-Weighted Average MG Activity of Daily Living (MG-ADL)

    Time frame: baseline, month 4, 6 and every 3 months through 36 months

    MG Activity of Daily Living total scores range from 0 to 24, with the lower scores indicating better daily living quality of life.

  17. Time-Weighted Average MG Activity of Daily Living (MG-ADL) at Month 12, 24, and 36

    Time frame: Month 12, 24, and 36

    MG Activity of Daily Living total scores range from 0 to 24 by visit, with the lower scores indicating better daily living quality of life.

  18. Azathioprine Use

    Time frame: baseline to 3 years

  19. Plasma Exchange Use

    Time frame: baseline to 3 years

  20. Intravenous Immunoglobulin Use

    Time frame: baseline to 3 years

  21. Minimal Manifestation (MM) Status at Month 12, 24 and 36

    Time frame: Month 12, 24 and 36

    Number of participants who were in minimal manifestation status at month 12, 24 and 36.

  22. Cumulative Days in Hospital for Myasthenia Gravis Exacerbation

    Time frame: baseline to 2 years

    Number of patients with MG exacerbation: Thymectomy plus prednisone=6 (out of 66); Prednisone alone=17 (out of 60)

  23. Cumulative Days in Hospital for Myasthenia Gravis Exacerbation

    Time frame: baseline to 3 years

    Number of patients with MG exacerbation: Thymectomy plus prednisone=6 (out of 66); Prednisone alone=22 (out of 60)

  24. Short Form-36 Standardized Physical Component

    Time frame: Month 0, Month 12, Month 24 and Month 36

    Range from 0 to 100, the higher the physical component value, the better the mental health.

  25. Short Form-36 Standardized Mental Component

    Time frame: Month 0, Month 12, Month 24 and Month 36

    Range from 0 to 100, the higher the mental component value, the better the mental health.

  26. Treatment Associated Complications (TAC)

    Time frame: Month 0, 1, 2, 3, 4 then every 3 months through Month 36

    Treatment associated complications measured complications occurred by myasthenia gravis patients. Report number of participant with at least one complications by each visit.

  27. Treatment Associated Symptoms (TAS)

    Time frame: Month 0, 1, 2, 3, 4 then every 3 months through Month 36

    Treatment associated symptoms measured myasthenia gravis symptoms such as back pain and/or bruises. Report number of participant with at least one treatment associated symptoms by each visit.

Sponsors and collaborators

Lead sponsor

University of Alabama at Birmingham

Other

Collaborators

  • National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Official study title

A Multi-Center, Single-Blind, Randomized Study Comparing Thymectomy to No Thymectomy in Non-Thymomatous Myasthenia Gravis (MG) Patients Receiving Prednisone

Important dates

Study start
2006
Primary completion
2015
Study completion
2015
First posted
Feb 22, 2006
Registry last updated
May 23, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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