Neoplasms

Nervous System Diseases

Immune System Diseases

All Conditions

Blood and Lymph Conditions

Musculoskeletal Diseases

Symptoms and General Pathology

Rare Diseases

Myasthenia Gravis

Thymoma

Thymus Neoplasms

Muscle Weakness

Paresis

Asthenia

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

All Drugs and Chemicals

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Prednisone

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Procedure: Extended Transsternal Thymectomy plus prednisone treatment

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

thymectomy plus prednisone

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

prednisone alone

Gary Cutter, PhD

Gil Wolfe, MD

Henry Kaminski, MD

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.

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.

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

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

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.

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.

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

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)

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

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.

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.

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.

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

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.

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

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

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

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

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

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

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.

National Institute of Neurological Disorders and Stroke (NINDS)

University of Alabama at Birmingham

Principle Investigator

There were two groups: 60 patients who received prednisone only and 66 patients had thymectomy plus prednisone

Procedure: Extended Transsternal Thymectomy plus prednisone treatment

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

Thymectomy Plus Prednisone

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.

Prednisone Alone

Total

Age, Continuous

Sex: Female, Male

Asian

Black

Hispanic

Non-Hispanic

Other

Race/Ethnicity, Customized

Argentina

United States

Japan

United Kingdom

Thailand

Canada

Netherlands

Brazil

Poland

Italy

Mexico

South Africa

Australia

Chile

Germany

Region of Enrollment

Missing

Therapy at enrollment - Pyridostigimine

Therapy at enrollment - Glucocorticoid

Previous therapy - Intravenous immue globulin

Previous therapy - Plasma exchange

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.

MGFA class

Duration of disease

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

QMG score

Prednisone use at baseline

Prednisone dosage unit as mg, patient has been taken prednisone every other day

Prednisone Dosage at baseline (mg)

Potential weakness of this trial include the single-blinded and pill count methodology.

Dr. Gary Cutter, Professor

Four participants in each group did not provide the information to enable calculation of the time-weighted Quantitative Myasthenia Gravis Weakness Score over 3 years.

Time-weighted Average Quantitative Myasthenia Gravis Weakness Score Over 3 Years

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of the time-weighted average alternate-day prednisone dose (mg) over 3 years.

Time-weighted Average Alternate-day Prednisone Dose (mg) Measured Over 3 Years

Not prednisone naïve

Prednisone naïve

Four participants in Thymectomy plus prednisone and 5 in Prednisone alone group did not provide information to enable the calculation of Time-weighted average Quantitative Myasthenia Gravis Score by prednisone use at enrollment over 3 years.

Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Prednisone Use at Enrollment

Female

Male

Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Sex

Age (years) at Disease Onset < 40

Age (years) at Disease Onset ≥ 40

Four participants in each group did not provide the information to enable calculation of the time-weighted average Quantitative Myasthenia Gravis Weakness Score over 3 years. Another 2 participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the age at disease onset information.

Subgroup Analyses of Time-weighted Average Quantitative Myasthenia Gravis Score by Age at Disease Onset

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of time-weighted average alternate-day prednisone dose (mg) over 3 years. Another 1 in Prednisone alone group did not provide prednisone use at enrollment information.

Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Prednisone Use at Enrollment

Subgroup Analyses of Time-weighted Average Alternate-day Prednisone Dose (mg) by Sex

Age (Years) at Disease Onset < 40

Age (Years) at Disease Onset ≥ 40

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of the time-weighted average alternate-day prednisone dose (mg) over 3 years. Another 2 in Thymectomy plus prednisone group and 4 in Prednisone alone group did not provide age at disease onset information.

Subgroup Analyses of Time-weighted Average Average Alternate-day Prednisone Dose (mg) by Age at Disease Onset

Number of Serious Adverse Events

Number of Patients With at Least One Serious Adverse Events

Life-threatening

Disability or incapacity

Medical or surgical intervention

Death

Complication due to thytmectomy

Hospitalization

One participant might had experienced more than one serious adverse event.

Classification of Serious Adverse Events

Months 0-24

Months 0-36

Number of participants who had hospitalized over 2 and 3 years

Hospitalization for Exacerbation of Myasthenia Gravis

Cumulative Number of Hospital Days

Gastrointestinal disorder

Hepatobiliary disorder

Infection or infestation

Injury, poisoning, or procedure complication

Metabolism or nutrition disorder

Nervous system disorder

Respiratory, thoracic, or mediastinal disorder

Surgical or medical procedure

Vascular disorder

Reason for Hospitalization According to Medical Dictionary for Regulatory Activities Term

Four participants in each group did not provide the information to enable calculation of the time-weighted average prescribed alternate-day prednisone dose (mg) over 3 years.

Time-weighted Average Prescribed Alternate Day Prednisone Dose (mg)

Five participants in Thymectomy plus prednisone and 4 in Prednisone alone group did not provide the information to enable calculation of the penalized time-weighted average alternate-day prednisone dose (mg) over 3 years.

Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 1: Penalized Using Maximum Dose Before Azathioprine)

Penalized Time-weighted Average Alternative Day Prednisone Dose (mg; Method 2: Penalized Using Dose at Time of Starting Azathioprine)

Five participants in each group did not provide the information to enable calculation of the time-weighted average MG activity of daily life over 3 years.

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

Month 12

Month 24

Month 36

Participants were in and out at month 12, 24 and 36 visit.

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

Azathioprine Use

Plasma Exchange Use

Intravenous Immunoglobulin Use

Number analyzed: Thymectomy plus prednisone: n=61 (Month 12), 59 (Month 24) , and 58 (Month 36); Prednisone alone n=54 (Month 12), 53 (Month 24), and 51 (Month 36)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy	NCT00294658	Myasthenia Grav...	thymectomy plus... prednisone alon...	18 Years - 65 Years	University of Alabama at Birmingham
Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy	NCT00294658	Myasthenia Grav...	thymectomy plus... prednisone alon...	18 Years - 65 Years	University of Alabama at Birmingham
Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy	NCT00294658	Myasthenia Grav...	thymectomy plus... prednisone alon...	18 Years - 65 Years	University of Alabama at Birmingham

Spots Global Cancer Trial Database for extended transsternal thymectomy