Comparison of Clinical Effects of Azathioprine and Rituximab NMO-SD Patients

NCT03002038 | Completed Phase 2 Results

• 1 other identifier: 395275
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare annual relapse rate, expanded disability status scale, and side effects of azathioprine and rituximab in patients with neuromyelitis optica spectrum disorder during a one year follow up through a randomized clinical trial.

Conditions

Neuromyelitis Optica Spectrum Disorder

Keywords

neuromyelitis optica spectrum disorder; azathioprine; rituximab; clinical trial; annual relapse rate; expanded disability status scale

Outcome Measures

Primary Outcomes (1)

• Annual Relapse Rate

  annual relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.

  one year

Secondary Outcomes (1)

• Expanded Disability Status Scale

  one year

Other Outcomes (1)

• Number of Participants With Adverse Drug Reactions

  one year

Study Arms (2)

Azathioprine

EXPERIMENTAL

Patients in this group will receive 50 mg of azathioprine, two times each day and gradually increased to maximum dose of 3 g daily with the aim of lymphocytes count less than 1500.

Drug: Azathioprine

Rituximab

EXPERIMENTAL

Patients in this group will receive 1g of Rituximab in 500 cc normal saline serum through intravenous infusion with two weeks intervals (as one course) and each course of treatment is repeated every 6 months.

Drug: Rituximab

Interventions

Azathioprine DRUG

Patients are started with Azathioprine 50 mg tablets, taken orally twice a day. The medication dose is increased gradually with the aim of lymphocytes count bellow 1500 and to the maximum dose of 3 g Azathioprine per day. Cell blood count is checked once a week in the first month of treatment, once every two weeks in the second month of treatment, and monthly in the third month of treatment to make decision about medication dose.

Also known as: Azathioprine Mehrdaru®

Azathioprine

Rituximab DRUG

Patients will receive 1 g of Rituximab (two vials of RediTux 500 mg/50 ml) in 500 cc normal saline serum through intravenous infusion and this will be repeated two weeks later. This cycle will be repeated every 6 months.

Also known as: RediTux®

Rituximab

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of neuromyelitis optica spectrum disorder based on the recent guidelines in 2015
• Expanded disability status scale between 0 and 7
• Age between 18 and 50 years old

You may not qualify if:

• Pregnancy or lactation during the study
• Deciding to leave the study by patient
• Lack of consent to enter the study
• Lack of cooperation for follow up
• Severe side effect of the medication
• Treatment with other immunosuppressant medications (including but not limited to cyclophosphamide, mycophenolate mofetil, methotrexate, others) within two months before intervention
• Taking any other immunosuppressant or other type of medication (including herbal drugs) without permission of the physician during the study.
• Presence of other autoimmune disease (including but not limited to Behcet disease, systemic lupus erythematosus, rheumatoid arthritis, and others)
• Presence of liver disorders
• Presence of hematologic disorders
• Presence of heart failure
• Receipt of a live vaccine within 4 weeks prior to intervention
• Previous treatment with Azathioporine or Rituximab
• History of HIV, hepatitis B, or hepatitis C
• Ongoing daily steroid use

Sponsors & Collaborators

• Isfahan University of Medical Sciences: lead

Study Sites (1)

Kashani Hospital

Isfahan, 8174673461, Iran

Location

Related Publications (7)

• Sato DK, Lana-Peixoto MA, Fujihara K, de Seze J. Clinical spectrum and treatment of neuromyelitis optica spectrum disorders: evolution and current status. Brain Pathol. 2013 Nov;23(6):647-60. doi: 10.1111/bpa.12087.

  PMID: 24118482 BACKGROUND

• Morrow MJ, Wingerchuk D. Neuromyelitis optica. J Neuroophthalmol. 2012 Jun;32(2):154-66. doi: 10.1097/WNO.0b013e31825662f1.

  PMID: 22617743 BACKGROUND

• Costanzi C, Matiello M, Lucchinetti CF, Weinshenker BG, Pittock SJ, Mandrekar J, Thapa P, McKeon A. Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology. 2011 Aug 16;77(7):659-66. doi: 10.1212/WNL.0b013e31822a2780. Epub 2011 Aug 3.

  PMID: 21813788 BACKGROUND

• Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kumpfel T; Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. 2014 Jan;261(1):1-16. doi: 10.1007/s00415-013-7169-7. Epub 2013 Nov 23.

  PMID: 24272588 BACKGROUND

• Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep 1;70(9):1110-7. doi: 10.1001/jamaneurol.2013.3071.

  PMID: 23897062 BACKGROUND

• Katz Sand I. Neuromyelitis Optica Spectrum Disorders. Continuum (Minneap Minn). 2016 Jun;22(3):864-96. doi: 10.1212/CON.0000000000000337.

  PMID: 27261687 BACKGROUND

• Nikoo Z, Badihian S, Shaygannejad V, Asgari N, Ashtari F. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial. J Neurol. 2017 Sep;264(9):2003-2009. doi: 10.1007/s00415-017-8590-0. Epub 2017 Aug 22.

  PMID: 28831548 DERIVED

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

Azathioprine; Rituximab; Reditux

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye 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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

lack of blinding, uneven assignment of patients to treatment groups, lack of compliance measures, and short follow-up duration

Results Point of Contact

• Title: Dr. Vahid Shaygannejad
• Organization: Isfahan University of Medical Sciences

shaygannejad@med.mui.ac.ir

+98 913 313 3550

Study Officials

• Vahid Shaygannejad, M.D.

  Department of Neurology, School of Medicine, Isfahan University of Medical Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: December 23, 2016
• Study Start: September 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 30, 2020
• Results First Posted: September 30, 2020

Record last verified: 2020-09

Locations

IR (1)