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Neuromyelitis Optica Spectrum DisorderPhase 2/3NCT03002038

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

A Phase 2/3 study testing Azathioprine and Rituximab in people with Neuromyelitis Optica Spectrum Disorder, run by Isfahan University of Medical Sciences at 1 site in Iran.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
Neuromyelitis Optica Spectrum Disorder
What is being tested?
Azathioprine and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
1 siteIran
Study dates
Sep 2015to Dec 2016
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 16Show fewer
  • 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
  • History of severe allergic or anaphylactic reaction to monoclonal antibodies

Trial locations and contacts

1 site in 1 country.

Iran1 site
  • Kashani Hospital

    Isfahan, 8174673461

Other trials in Iran

About this study

Official title: Comparison of Annual Relapse Rate, Expanded Disability Status Scale, and Side Effects Between Azathioprine and Rituximab in Patients With Neuromyelitis Optica Spectrum Disorders

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.

Read the detailed description

Neuromyelitis Optica Spectrum Disorder (NMO-SD) is a recurrent inflammatory demyelinating disease affecting the central nervous system. The disease is clinically recognized by optic neuritis and transverse myelitis and is associated with high risk of mortality. Each attack worsens patients' disability. This means that after 5 years of the disease onset, half of patients need to use wheelchair and approximately 50% of them become blind.

Considering that the disease can be disabling for patients, the maintenance treatment should be applied in addition to treatment of acute attacks, in order to prevent future recurrences. Acute attacks are usually treated with high doses of intravenous corticosteroids. Plasmapheresis is also used when patients fail to response to corticosteroids. B lymphocyte inhibitors are used as the maintenance therapy in these patients. First line therapeutic medications include azathioprine and rituximab which are being recommended for long term therapy and second line medications include methotrexate and mycophenolate mofetil.

Azathioprine is an immune-modulatory agent which is available in the oral form and don't require hospitalization to be administered, however, because of side effects such as bone marrow suppression and hepatotoxicity, periodic check of blood cells and liver enzymes are needed. Rituximab is a cluster of differentiation antigen 20 inhibitor which leads to decreased B lymphocytes and antibody in patients. This medication is only available in the injectable form and needs hospitalization to be administered. Close monitory is needed during the administration considering severe side effects such as allergic reactions and respiratory distress. However, laboratory tests are not needed in patients taking rituximab although it is more expensive than azathioprine. No clinical trial has been performed previously to compare clinical efficacy of these two drugs in NMO-SD patients. Therefore, we aimed to compare their efficacy through a randomized clinical trial.

Being tested
Azathioprine, Rituximab
Keywords
neuromyelitis optica spectrum disorder, azathioprine, rituximab, clinical trial, annual relapse rate, expanded disability status scale
Medical subject headings
Neuromyelitis Optica

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzathioprineDrug

    Also called Azathioprine Mehrdaru®

    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.

  • RituximabDrug

    Also called RediTux®

    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.

Study groups in NCT03002038
Study groupRoleWhat they receive
AzathioprineExperimentalPatients 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.
Receives: Drug: Azathioprine
RituximabExperimentalPatients 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.
Receives: Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: one year

Secondary outcomes (1)
  1. Expanded Disability Status Scale

    expanded disability status scale will be measured in the baseline and after 12 months of intervention.

    Expanded disability status scale (EDSS) is a measure of disability for patients. The score ranges from 0-10, with 0 showing normal neurological exam and 10 showing death due to the disabling disease. Thus, higher scores represent more profound levels of disability.

    Measured: one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2016 (estimated)
  2. Study startSep 2015
  3. Primary completionNov 2016
  4. Study completionDec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03002038
Sponsor's protocol ID
395275
Status last verified
Sep 2020
First submitted
21 Dec 2016
Last updated
30 Sep 2020
Data monitoring committee
No
Individual data sharing
Undecided: We may share the individual participant data (anonymously) on request of the journal publishing the study report.

Publications

  • 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.

    PubMed 24118482
  • Morrow MJ, Wingerchuk D. Neuromyelitis optica. J Neuroophthalmol. 2012 Jun;32(2):154-66. doi: 10.1097/WNO.0b013e31825662f1.

    PubMed 22617743
  • 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.

    PubMed 21813788
  • 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.

    PubMed 24272588
  • 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.

    PubMed 23897062
  • Katz Sand I. Neuromyelitis Optica Spectrum Disorders. Continuum (Minneap Minn). 2016 Jun;22(3):864-96. doi: 10.1212/CON.0000000000000337.

    PubMed 27261687
  • 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.

    PubMed 28831548

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Azathioprine and Rituximab in people with Neuromyelitis Optica Spectrum Disorder, run by Isfahan University of Medical Sciences at 1 site in Iran.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annual Relapse Rate (time frame: one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03002038, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2020.

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