Clinical trial NCT00997412: Trial of Mycophenolic Acid Versus Azathioprine in the Treatment of Corticosteroid-refractory Myasthenia Gravis
Official title: Randomized, Double-blind, Double-dummy Trial of Mycophenolic Acid Versus Azathioprine in the Treatment of Corticosteroid-refractory Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Myasthenia Gravis
Lead sponsor: Qualitix Clinical Research Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2009-10-19
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is an randomized, double-blind, double-dummy trial, and the objective is to compare the efficacy and safety of Mycophenolic acid (MA) and Azathioprine (AZA), immunosuppressive drugs, in myasthenia gravis patients. This prospective study will enroll 40 myasthenia gravis (MG) patients who are poor controlled under prior steroid therapy. All subjects should be randomly assigned to MA group and AZA group that will receive routine pyridostigmine and prednisolone in combination with MA or AZA.

Detailed description: This will be a double-dummy study to keep the blinded quality.

* MA group: 1 tablet AZA placebo and 4 tables MA (180 mg/tab,720 mg/day) twice daily.
* AZA group: 1 tablet AZA (50mg/tab) and 4 tables MA placebo twice daily.

  * When patients achieve minimal manifestation (MM, i.e. complete remission), which lead to normal daily routine, the dose of pyridostigmine should reduce to 240 mg/day (4 tablets) or less. The dose of steroid should be stepped down by 10 mg qod (every other day) for every 2 weeks until the dose achieves 40 mg qod. After that, the dose should be stepped down by 5 mg qod for every month.
  * When disease progresses and is no longer maintaining minimal manifestation, the dose of steroid will be stepped up by 10 mg qod for every 2 weeks until achieve clinical stable remission. The taper rule of steroid could start again 1 month after stabilization.
  * Every patient will be treated for 1 year. If the patient could not achieve MM within 1 year, the blind of individual patient will be opened and the patients will be crossed over to another medical treatment. The efficacy and safety of second medication will be observed openly until the end of study.
  * When the muscle weakness worsens under established study schedule, plasmapheresis could be conducted to improve the condition rapidly.

Eligibility criteria: Inclusion Criteria:

* Male or female age between 20-70 (including 20 and 70 years old).
* Osserman II and III Myasthenia Gravis.
* Positive serum anti-acetylcholine receptor antibodies.
* Poor control of disease with daily dose of prednisone ≥ 30 mg or 0.5 mg/kg at 3 months before enrollment.
* Without immunosuppressive therapy other than steroid.

Exclusion Criteria:

* Ocular MG or minimal clinical syndrome that would not require the therapy of steroids.
* Negative serum anti-acetylcholine receptor antibodies.
* Use immunosuppressants other than steroids in the preceding year.
* Previous use other investigational medication within 3 months or current participate other clinical study.
* Poor renal function: serum creatinine \> 3.0 mg/dl or estimated creatinine clearance \< 30 ml/min
* Females who are pregnancy or breast-feeding.
* Recent history, within 5 years, of malignancy
* Unwilling or unable to participate the necessary continuous visits and examinations.

Primary outcomes:
measure: The ratio of two arms patients achieve minimal manifestation (MM, i.e. complete remission)
timeFrame: One year after treatment
Secondary outcomes:
measure: Osserman clinical classification
timeFrame: One year after treatment
measure: Myasthenia gravis (MG) score
timeFrame: One year after treatment
Other outcomes:
Locations:
Study officials:
affiliation: Shin Kong Wu Ho-Su Memorial Hospital
name: Jiann-Horng Yeh, M.D.
role: PRINCIPAL_INVESTIGATOR
References: