The Efficacy and Safety of Leflunomide or Azathioprine Therapy in Myasthenia Gravis Patients After Expand Thymectomy

NCT01727193 | Completed Phase 3 DMC

• 1 other identifier: ZS-LEF
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized controlled clinical study. The investigators screen of eligible patients, randomized divide into the following two groups: corticosteroids + azathioprine group, corticosteroids + leflunomide group. The investigators treat the enrolled patients, estimate efficacy and observed the side effects according to the requirements of program. The investigators establish a clinical database for recording patients date and statistical analysis. Evaluation of short-term and long-term efficacy of thymectomized myasthenia gravis patients in the different group prove that what kind of treatment can improve the cure rate. The investigators will evaluate the acute toxicity (gastrointestinal side effects, liver and kidney dysfunction) and long-term toxicity (immune dysfunction, gonadal suppression) when the investigators apply these therapy in the treatment of different clinical types of myasthenia gravis.

Conditions

Myasthenia Gravis

Keywords

myasthenia gravis; leflunomide

Outcome Measures

Primary Outcomes (1)

• the percent of achieving good response

  Pharmacologic Remission (PR) was the primary efficacy endpoint observed. Record the time the patient appears from the time of medication to the time of PR, and calculate the percentage of PR patients in each arm. Criteria for PR: The patient has had no symptoms or signs of MG for at least 1 year and continues to take some form of therapy for MG. There is no weakness of any muscle on careful examination by someone skilled in the evaluation of neuromuscular disease. Isolated weakness of eyelid closure is accepted. Patients taking cholinesterase inhibitors are excluded from this category because their use suggests the presence of weakness.

  144 weeks

Secondary Outcomes (1)

• The changes of the disease severity and the antibody titer during the follow-up

  144 weeks

Study Arms (2)

Azathioprine

ACTIVE COMPARATOR

cholinesterase inhibitors+Glucocorticoid +Azathioprine

Drug: Azathioprine

Leflunomide

ACTIVE COMPARATOR

cholinesterase inhibitors+glucocorticoid+Leflunomide

Drug: Leflunomide

Interventions

Azathioprine DRUG

The basic therapy of each group is cholinesterase inhibitors (pyridostigmine 36mg / kg / d). Group 1 glucocorticoid + Azathioprine: Glucocorticoid (0.25mg/kg/d )plus Azathioprine at a starting dose of 50mg/d for 14 days, then increase up to 2mg/kg in 2 weeks.If no adverse events occurred , maintain the dose until 48 weeks.

Azathioprine

Leflunomide DRUG

The basic therapy of each group is cholinesterase inhibitors (pyridostigmine 36mg / kg / d). Group 2 glucocorticoid + Leflunomide: Glucocorticoid (0.25mg/kg/d )plus Leflunomide 20mg/d for adult, 10mg/d for child. if no adverse events occurred , maintain the dose until 48 weeks.

Leflunomide

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• to 65 years；
• Myasthenia gravis:
• Patients who are diagnosed as generalized or ocular myasthenia gravis
• have experienced extended thymectomy (including thymic hyperplasia and thymoma)， no significant complications in 6 months after operation , and does not received any immunosuppressants or glucocorticoids treatments.
• do not applied in plasmapheresis or immunoglobulins treatment during 3 months .
• women of child-bearing period do not have a plan of pregnant for at least 3 year.
• Written consent of the patient, after informing

You may not qualify if:

• The liver , kidney or glycometabolic function is abnormal
• Seriously complications, such as infection or symptom in central nervous system,
• The patients who suffering from malignancy or a history of malignancy, a variety of sexually transmitted diseases and HIV infection, tuberculosis infection, and other condition which need to prohibit the use of immunosuppressive patients.
• Be allergic to leflunomide, azathioprine
• Pregnant or suckling period woman
• Accompanied with mental disorders and have difficult to communication
• Experienced myasthenia crisis in 3 months.
• suffering from clear cardiopulmonary functional and brain abnormalities
• Have a history of refractory hypertension or peptic ulcer .
• One of the white blood cells, hemoglobin, and platelet count obvious abnormalities

Sponsors & Collaborators

• First Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

The First Affiliated Hospital, SUN YAT-SEN UNIVERSITY

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Azathioprine; Leflunomide

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Weibin Liu, Doctor

  First Affiliated Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 8, 2012
• First Posted: November 15, 2012
• Study Start: September 1, 2012
• Primary Completion: October 18, 2021
• Study Completion: November 18, 2021
• Last Updated: April 14, 2022

Record last verified: 2022-04

Locations

CN (1)