Trial Outcomes & Findings for Comparison of Clinical Effects of Azathioprine and Rituximab NMO-SD Patients (NCT NCT03002038)
NCT ID: NCT03002038
Last Updated: 2020-09-30
Results Overview
annual relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
86 participants
Primary outcome timeframe
one year
Results posted on
2020-09-30
Participant Flow
Participant milestones
| Measure |
Azathioprine
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.
Azathioprine: 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.
|
Rituximab
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.
Rituximab: 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.
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
40
|
|
Overall Study
COMPLETED
|
35
|
33
|
|
Overall Study
NOT COMPLETED
|
11
|
7
|
Reasons for withdrawal
| Measure |
Azathioprine
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.
Azathioprine: 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.
|
Rituximab
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.
Rituximab: 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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
8
|
4
|
|
Overall Study
Immigration to another region
|
0
|
2
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Azathioprine
n=46 Participants
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.
Azathioprine: 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.
|
Rituximab
n=40 Participants
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.
Rituximab: 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.
|
Total
n=86 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32.11 years
STANDARD_DEVIATION 9.36 • n=46 Participants
|
34.33 years
STANDARD_DEVIATION 5.86 • n=40 Participants
|
33.14 years
STANDARD_DEVIATION 7.32 • n=86 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=46 Participants
|
34 Participants
n=40 Participants
|
72 Participants
n=86 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=46 Participants
|
6 Participants
n=40 Participants
|
14 Participants
n=86 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Iran
|
46 participants
n=46 Participants
|
40 participants
n=40 Participants
|
86 participants
n=86 Participants
|
|
Expanded disability status scale
|
2.40 units on a scale
STANDARD_DEVIATION 1.24 • n=35 Participants • Per reviewer's comment and to provide consistent results, we changed the baseline info for EDSS to per protocol analysis rather than intended to treat analysis. That's why the numbers decreased in each group.
|
3.55 units on a scale
STANDARD_DEVIATION 1.95 • n=33 Participants • Per reviewer's comment and to provide consistent results, we changed the baseline info for EDSS to per protocol analysis rather than intended to treat analysis. That's why the numbers decreased in each group.
|
2.96 units on a scale
STANDARD_DEVIATION 1.52 • n=68 Participants • Per reviewer's comment and to provide consistent results, we changed the baseline info for EDSS to per protocol analysis rather than intended to treat analysis. That's why the numbers decreased in each group.
|
|
Annualized relapse rate
|
1.02 numbers of relapses
STANDARD_DEVIATION 0.39 • n=46 Participants
|
1.30 numbers of relapses
STANDARD_DEVIATION 0.65 • n=40 Participants
|
1.15 numbers of relapses
STANDARD_DEVIATION 0.51 • n=86 Participants
|
|
Positive AQP4-IgG
|
25 Participants
n=46 Participants
|
17 Participants
n=40 Participants
|
42 Participants
n=86 Participants
|
PRIMARY outcome
Timeframe: one yearPopulation: Per protocol analysis
annual relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.
Outcome measures
| Measure |
Azathioprine
n=35 Participants
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.
Azathioprine: 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.
|
Rituximab
n=33 Participants
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.
Rituximab: 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.
|
|---|---|---|
|
Annual Relapse Rate
Baseline
|
1 Number of relapses
Standard Deviation 0.38
|
1.30 Number of relapses
Standard Deviation 0.68
|
|
Annual Relapse Rate
Outcome
|
0.51 Number of relapses
Standard Deviation 0.55
|
0.21 Number of relapses
Standard Deviation 0.42
|
SECONDARY outcome
Timeframe: one yearPopulation: Per protocol analysis
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.
Outcome measures
| Measure |
Azathioprine
n=35 Participants
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.
Azathioprine: 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.
|
Rituximab
n=33 Participants
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.
Rituximab: 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.
|
|---|---|---|
|
Expanded Disability Status Scale
Baseline
|
2.40 score on a scale
Standard Deviation 1.24
|
3.55 score on a scale
Standard Deviation 1.95
|
|
Expanded Disability Status Scale
Outcome
|
1.95 score on a scale
Standard Deviation 1.13
|
2.56 score on a scale
Standard Deviation 1.99
|
OTHER_PRE_SPECIFIED outcome
Timeframe: one yearPopulation: intention to treat analysis
adverse drug reactions will be observed closely and reported during the intervention. We will compare the number of adverse drug reactions in two groups. Also, adverse drug reactions will be described by details in each group.
Outcome measures
| Measure |
Azathioprine
n=46 Participants
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.
Azathioprine: 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.
|
Rituximab
n=40 Participants
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.
Rituximab: 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.
|
|---|---|---|
|
Number of Participants With Adverse Drug Reactions
|
3 Participants
|
4 Participants
|
Adverse Events
Azathioprine
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Rituximab
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Azathioprine
n=46 participants at risk
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.
Azathioprine: 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.
|
Rituximab
n=40 participants at risk
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.
Rituximab: 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.
|
|---|---|---|
|
Hepatobiliary disorders
Impaired liver function test
|
2.2%
1/46 • Number of events 1 • 1 year
|
0.00%
0/40 • 1 year
|
|
Immune system disorders
Severe allergic reaction
|
0.00%
0/46 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Azathioprine
n=46 participants at risk
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.
Azathioprine: 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.
|
Rituximab
n=40 participants at risk
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.
Rituximab: 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.
|
|---|---|---|
|
Immune system disorders
Mild/moderate allergic reactions
|
0.00%
0/46 • 1 year
|
7.5%
3/40 • Number of events 3 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal intolerance
|
4.3%
2/46 • Number of events 2 • 1 year
|
0.00%
0/40 • 1 year
|
Additional Information
Dr. Vahid Shaygannejad
Isfahan University of Medical Sciences
Phone: +98 913 313 3550
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place