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

NCT00294658 | Completed Phase 3 Results DMC

• 3 other identifiers: R01NS0507331U01NS042685-01A2CRC
• Study Type: interventional
• Target: 126
• Locations: 18 countries
• Sites: 70

Brief Summary

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.

Conditions

Myasthenia Gravis

Keywords

myasthenia gravis; thymectomy; prednisone; corticosteroid; extended transsternal thymectomy; ETTX; MG; thymus; thymoma

Outcome Measures

Primary Outcomes (2)

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

  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.

  baseline, month 3, 4, 6 and every 3 months through 36 months

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

  Participants reported alternate-day prednisone dose (mg) intake from baseline through withdrawn or completed 3 years follow up.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.

  baseline, month 1 , 2 , 3, 4, 6 and every 3 months through 36 months

Secondary Outcomes (27)

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

  baseline, month 3, 4, 6 and every 3 months through 36 months

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

  baseline, month 3, 4, 6 and every 3 months through 36 months

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

  baseline, month 3, 4, 6 and every 3 months through 36 months

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

  baseline, month 3, 4, 6 and every 3 months through 36 months

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

  baseline, month 3, 4, 6 and every 3 months through 36 months

Study Arms (2)

Thymectomy plus prednisone

ACTIVE COMPARATOR

Procedure: Extended Transsternal Thymectomy plus prednisone treatment

Procedure: thymectomy plus prednisone

Prednisone alone

PLACEBO COMPARATOR

Drug: prednisone alone protocol

Drug: prednisone alone

Interventions

thymectomy plus prednisone PROCEDURE

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

Also known as: Extended transsternal thymectomy plus prednisone

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.

Also known as: prednisolone

Prednisone alone

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (70)

University of Alabama at Birmingham, Department of Neurology, Sparks Center, Suite 350, 1720 7th Avenue South

Birmingham, Alabama, 35233, United States

Location

Data Coordination Center: University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Barrow Neurological Institute, Saint Joseph's Hospital and Medical Center, 350 W Thomas Rd

Phoenix, Arizona, 85016, United States

Location

University of Southern California, Doheny Institute, 1450 San Pablo St

Los Angeles, California, 90033, United States

Location

University of California Irvine, 101 The City Drive S, Bldg. 22 C, Route 13

Orange, California, 92868, United States

Location

California Pacific Medical Center, Castro St & Duboce Ave

San Francisco, California, 94114, United States

Location

University of Florida Jacksonville, Tower I, 8th Floor, 580 W. 8th ST.

Jacksonville, Florida, 32209, United States

Location

University of Miami, 1120 NW 14th Street, Suite 1300

Miami, Florida, 33136, United States

Location

Emory University, 201 Dowman Dr

Atlanta, Georgia, 30322, United States

Location

Augusta University, 1120 15th St

Augusta, Georgia, 30912, United States

Location

Indiana University, Dept of Neurology, Regenstrief Health Center, 6th floor, 1050 Walnut St, Indiana University Medical Center

Indianapolis, Indiana, 46202-2859, United States

Location

The University of Kansas Medical Center, 3901 Rainbow Blvd.

Kansas City, Kansas, 66160, United States

Location

Brigham and Women's Hospital, 75 Francis Street, 5th Floor Tower

Boston, Massachusetts, 02115-6110, United States

Location

Wayne State University School of Medicine, 4201 St Antoine, 8D UHC

Detroit, Michigan, 48201, United States

Location

William Beaumont Hospital, 3601 W. Thirteen Mile Road, Royal Oak

Royal Oak, Michigan, 48073, United States

Location

University of Minnesota, Department of Neurology, MMC 295, 420 Delaware St. S.E.,

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Rochester, 200 First St. SW

Rochester, Minnesota, 55905, United States

Location

St. Louis University, One North Grand St. Louis

St Louis, Missouri, 63103-2097, United States

Location

Robert Wood Johnson University,

New Brunswick, New Jersey, 08901, United States

Location

Mount Sinai Hospital,1 Gustave L. Levy Pl

New York, New York, 10029, United States

Location

University of Rochester, 601 Elmwood Ave

Rochester, New York, 14642, United States

Location

Duke University, 200 Trent Dr

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University, University Hospitals of Cleveland, 1100 Euclid Avenue

Cleveland, Ohio, 44106, United States

Location

The Ohio State University Wexmer Medical Center, Rm 461 Means Hall, The Ohio State University Medical Center,1654 Upham Dr.

Columbus, Ohio, 43210, United States

Location

University of Texas Southwestern Medical Center, 5232 Harry Hines Blvd,

Dallas, Texas, 75390-8897, United States

Location

University of Texas Medical Branch, 301 University Blvd

Galveston, Texas, 77555-0539, United States

Location

Nerve and Muscle Center of Texas, 6624 Fannin St # 1670

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center, Mail code 7883, 7703 Floyd Curl Drive

San Antonio, Texas, 78229-3900, United States

Location

University of Vermont College of Medicine, Given Bldg C225, 89 Beaumont Avenue

Burlington, Vermont, 05405, United States

Location

University of Virginia, 1215 Lee St

Charlottesville, Virginia, 22908, United States

Location

University of Washington, 1410 NE Campus Pkwy

Seattle, Washington, 98195, United States

Location

West Virginia University, Dept of Neurology, WVU Eye Institute, Neurology Suite, 1 Stadium Drive,

Morgantown, West Virginia, 26506, United States

Location

Medical College of Wisconsin, 8701 Watertown Plank Road

Milwaukee, Wisconsin, 53226, United States

Location

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

Buenos Aires, Argentina

Location

University of Sydney, Royal Prince Alfred Hospital and The University of Sydney

Sydney, Australia

Location

University of Melbourne, Melbourne, The Royal Melbourne Hospital, Dept of Neurology, Royal Melbourne Hospital

Victoria, 3050, Australia

Location

Hospital de Base do Distrito Federal

Brasília, CEP 71640 255, Brazil

Location

Universidade Federal do Parana

Curitiba, 80060-900, Brazil

Location

Federal University of Rio De Janeiro

Rio de Janeiro, CEP 20520-053, Brazil

Location

University of Calgary, Heritage Medical Research Clinic Room 1132 3330 Hospital Dr NW

Calgary, Alberta, T2N 2T9, Canada

Location

University of British Columbia

Vancouver, British Columbia, V6T 2B5, Canada

Location

University of Ottawa, The Ottawa Hospital General Campus, Division of Neurology, 501 Smyth Rd. Box 601

Ottawa, Ontario, K1H 8L6, Canada

Location

McGill University Health Center

Montreal, Quebec, H3G 1A4, Canada

Location

Hospital Del Salvador, Departamento de Ciencias Neurológicas, Universidad de Chile, Salvador 95 Of 416, Providencia

Santiago, Chile

Location

University of Heidelberg, Seminarstraße 2

Mannheim, Baden-Wurttemberg, 69117, Germany

Location

University of Regensburg, Dept. of Neurology, Universitätsstr. 84, D

Regensburg, Bavaria, 93043, Germany

Location

University of Düsseldorf

Düsseldorf, North Rhine-Westphalia, D-40225, Germany

Location

Johannes-Gutenberg University, Klinikum der Johannes Gutenberg-Universität, Klinik und Poliklinik für Neurologie, Langenbeckstr

Mainz, Rhineland-Palatinate, 55101, Germany

Location

University of Münster, Schlossplatz 2

Münster, 48149, Germany

Location

University of Tübingen

Tübingen, 72076, Germany

Location

National Neurological Institute "Carlo Besta", Myopathology and Immunology Unit, Dept of Neurology IV, Natl. Neurolog Inst. "C. Besta", Via Celoria, 11,

Milan, 20133, Italy

Location

University of Rome "Sapienza"

Rome, 00189, Italy

Location

Catholic University, Universita Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, e

Rome, Italy

Location

University of Torino

Torino, Italy

Location

Kanazawa University, Department of Neurology, Kanazawa University Hospital, 13-1 Takaramachi

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Nagasaki University, First Department of Internal Medicine,Graduate School of Biomedical Sciences,1-7-1,Sakamoto

Nagasaki, Kyushu, 852-8501, Japan

Location

Instituto Nacional de la Nutrición

México, 14000, Mexico

Location

Leiden University

Leiden, Netherlands

Location

Medical University of Warsaw

Warsaw, Województwo, 02 097, Poland

Location

Institute of Tuberculosis and Lung Disease

Warsaw, Województwo, Poland

Location

Porto University, Serviço de Neurologia,Hospital Geral de Santo António, Largo Prof Abel Salazar

Porto, 4099-001, Portugal

Location

University of Cape Town, Division of Neurology E8-74, Groote Schuur Hospital,Observatory

Cape Town, South Africa

Location

H. Sant Pau, Universitat Autònoma de Barcelona, Neurology Department, Hospital Sta Creu i Sant Pau, C/Mas Casanovas no 90 4o pis 4o modul.

Barcelona, 08025, Spain

Location

Fu-Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist

New Taipei City, 24205, Taiwan

Location

Ramathibodi Hospital, Mahidol University

Bangkok, 10400, Thailand

Location

Queen Elizabeth University Hospital, Glasgow

Glasgow, G51 4TF, United Kingdom

Location

Walton Centre for Neurology and Neurosurgery, Liverpool Heart and Chest Hospital, Liverpool. The Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley

Liverpool, L9 7LJ, United Kingdom

Location

University of Manchester, Oxford Road

Manchester, M13 9PL, United Kingdom

Location

University of Oxford, Dept of Clinical Neurology, University of Oxford, Radcliffe Infirmary

Oxford, OX2 6HE, United Kingdom

Location

University of Sheffield, Western Bank

Sheffield, S10 2TN, United Kingdom

Location

Related Publications (7)

• Aban IB, Wolfe GI, Cutter GR, Kaminski HJ, Jaretzki A 3rd, Minisman G, Conwit R, Newsom-Davis J; Mgtx Advisory Committee. The MGTX experience: challenges in planning and executing an international, multicenter clinical trial. J Neuroimmunol. 2008 Sep 15;201-202:80-4. doi: 10.1016/j.jneuroim.2008.05.031.

  PMID: 18675464 RESULT

• Newsom-Davis J, Cutter G, Wolfe GI, Kaminski HJ, Jaretzki A 3rd, Minisman G, Aban I, Conwit R. Status of the thymectomy trial for nonthymomatous myasthenia gravis patients receiving prednisone. Ann N Y Acad Sci. 2008;1132:344-7. doi: 10.1196/annals.1405.014.

  PMID: 18567886 RESULT

• Minisman G, Bhanushali M, Conwit R, Wolfe GI, Aban I, Kaminski HJ, Cutter G. Implementing clinical trials on an international platform: challenges and perspectives. J Neurol Sci. 2012 Feb 15;313(1-2):1-6. doi: 10.1016/j.jns.2011.10.004. Epub 2011 Nov 1.

  PMID: 22047648 RESULT

• Kaminski HJ, Kusner LL, Wolfe GI, Aban I, Minisman G, Conwit R, Cutter G. Biomarker development for myasthenia gravis. Ann N Y Acad Sci. 2012 Dec;1275(1):101-6. doi: 10.1111/j.1749-6632.2012.06787.x.

  PMID: 23278584 RESULT

• Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, Strobel P, Mazia C, Oger J, Cea JG, Heckmann JM, Evoli A, Nix W, Ciafaloni E, Antonini G, Witoonpanich R, King JO, Beydoun SR, Chalk CH, Barboi AC, Amato AA, Shaibani AI, Katirji B, Lecky BR, Buckley C, Vincent A, Dias-Tosta E, Yoshikawa H, Waddington-Cruz M, Pulley MT, Rivner MH, Kostera-Pruszczyk A, Pascuzzi RM, Jackson CE, Garcia Ramos GS, Verschuuren JJ, Massey JM, Kissel JT, Werneck LC, Benatar M, Barohn RJ, Tandan R, Mozaffar T, Conwit R, Odenkirchen J, Sonett JR, Jaretzki A 3rd, Newsom-Davis J, Cutter GR; MGTX Study Group. Randomized Trial of Thymectomy in Myasthenia Gravis. N Engl J Med. 2016 Aug 11;375(6):511-22. doi: 10.1056/NEJMoa1602489.

  PMID: 27509100 RESULT

• Lee I, Kuo HC, Aban IB, Cutter GR, McPherson T, Kaminski HJ, Sussman J, Strobel P, Oger J, Cea G, Heckmann JM, Evoli A, Nix W, Ciafaloni E, Antonini G, Witoonpanich R, King JO, Beydoun SR, Chalk CH, Barboi AC, Amato AA, Shaibani AI, Katirji B, Lecky BRF, Buckley C, Vincent A, Dias-Tosta E, Yoshikawa H, Waddington-Cruz M, Pulley MT, Rivner MH, Kostera-Pruszczyk A, Pascuzzi RM, Jackson CE, Verschuuren JJG, Massey JM, Kissel JT, Werneck LC, Benatar M, Barohn RJ, Tandan R, Mozaffar T, Conwit R, Minisman G, Sonett JR, Wolfe GI; MGTX study group. Minimal manifestation status and prednisone withdrawal in the MGTX trial. Neurology. 2020 Aug 11;95(6):e755-e766. doi: 10.1212/WNL.0000000000010031. Epub 2020 Jul 1.

  PMID: 32611638 DERIVED

• Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, Strobel P, Mazia C, Oger J, Cea JG, Heckmann JM, Evoli A, Nix W, Ciafaloni E, Antonini G, Witoonpanich R, King JO, Beydoun SR, Chalk CH, Barboi AC, Amato AA, Shaibani AI, Katirji B, Lecky BRF, Buckley C, Vincent A, Dias-Tosta E, Yoshikawa H, Waddington-Cruz M, Pulley MT, Rivner MH, Kostera-Pruszczyk A, Pascuzzi RM, Jackson CE, Verschuuren JJGM, Massey JM, Kissel JT, Werneck LC, Benatar M, Barohn RJ, Tandan R, Mozaffar T, Silvestri NJ, Conwit R, Sonett JR, Jaretzki A 3rd, Newsom-Davis J, Cutter GR; MGTX Study Group. Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial. Lancet Neurol. 2019 Mar;18(3):259-268. doi: 10.1016/S1474-4422(18)30392-2. Epub 2019 Jan 25.

  PMID: 30692052 DERIVED

MeSH Terms

Conditions

Myasthenia Gravis; Thymoma

Interventions

Thymectomy; Prednisone; Prednisolone

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; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Thymus Neoplasms; Thoracic Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Thoracic Surgical Procedures; Surgical Procedures, Operative; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Limitations and Caveats

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

Results Point of Contact

• Title: Dr. Gary Cutter, Professor
• Organization: University of Alabama at Birmingham

cutter@uab.edu

205-975-5048

Study Officials

• Gary Cutter, PhD

  University of Alabama at Birmingham School of Public Health, Department of Biostatistics

  PRINCIPAL INVESTIGATOR

• Gil Wolfe, MD

  University of Buffalo, Jacobs School of Medicine and Biomedical Sciences

  PRINCIPAL INVESTIGATOR

• Henry Kaminski, MD

  George Washington University School of Medicine and Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: February 21, 2006
• First Posted: February 22, 2006
• Study Start: June 1, 2006
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 23, 2017
• Results First Posted: January 16, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (6); IT (4); TW (1); PL (2); US (33); BR (3); ZA (1); JP (2); AU (2); NL (1); PT (1); TH (1); ES (1); CA (4); CL (1); AR (1); ME (1); GB (5)