Systemic Lupus Erythematosus
Conditions
Keywords
Cyclophosphamide, genotype-based therapy, prospective study
Brief summary
The purpose of this study is to compare the genotype-based personal prescription of cyclophosphamide with the traditional prescription.
Detailed description
Cyclophosphamide (CPA) has been one of the most successful therapies for severe Systemic lupus erythematosus (SLE). However, cyclophosphamide can cause severe side effects, including bone marrow suppression, infection, gastrointestinal reaction, hemorrhagic cystitis, and the etc. Significant variation in efficacy and toxicity of CPA has been observed. Since the development of applicable therapeutic drug monitoring (TDM) of cyclophosphamide has been reported, it will help to improve the efficacy and reduce toxicities in SLE treatment. However, the TDM is a passive strategy which usually lags behind the appearance of toxicities. Therefore，it is especially crucial to give individuals genotype-based personal prescription of cyclophosphamide in order to gain the most effective therapies. Thus, the purpose of this study is to compare the genotype-based personal prescription of cyclophosphamide with the traditional prescription, in order to verify the efficacy of the genotype-based personal prescription.
Interventions
GENETICGenotype Detection
To Genotype cases in the experimental group and divide them into three groups, including extensive metaboliser (EM), intermediate metaboliser (IM) and poor metaboliser (PM).
Sponsors
First Affiliated Hospital, Sun Yat-Sen University
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* The American College of Rheumatology established eleven criteria in 1982,which were revised in 1997 as a classificatory instrument to operationalise the definition of SLE in clinical trials. 1. Malar rash (rash on cheeks). 2. Discoid rash (red, scaly patches on skin that cause scarring). 3. Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart). 4. Oral ulcers (includes oral or nasopharyngeal ulcers). 5. Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion. 6. Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups). 7. Blood-hematologic disorder-hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count\<4000/µl), lymphopenia (\<1500/µl) or thrombocytopenia (\<100000/µl) in the absence of offending drug. Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE. 8. Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in urine under a microscope. 9. Antinuclear antibody test positive. 10. Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid antibody, and/or false positive serological test for syphilis. Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons). 11. Neurologic disorder: Seizures or psychosis. For the purpose of identifying patients for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions. In the meantime, the case has one of the following conditions or more; <!-- --> 1. HIV (-); 2. Signed the informed consent; 3. Taking contraceptive measures during treatment period.
Exclusion criteria
* Poor compliance; * With lupus mental damage complication, occurrence of epilepsy or unable to express subjective symptoms during the observation period. * Taking drugs that affect cytochrome P450 2B6, cytochrome P450 3A4 and cytochrome P450 2C19, except corticosteroids. * Abnormal liver function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Reaction (Leucopenia) | one month | The count of white cells \< 4.0 × 10ˆ9/L in SLE patient who received CPA medication was considered as CPA-induced leucopenia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Reaction ( Infection ) | one month | Flu-like symptoms, Upper respiratory tract infection，and the etc. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group 45 cases in control group received traditional therapy that the initial dose of cyclophosphamide (CPA) was 0.2-0.6g/week injection according to clinical experience. | 45 |
| Experimental Group 47 cases in experimental group were genotyped as extensive metaboliser (EM), intermediate metaboliser (IM) and poor metaboliser (PM）with initial dose of CPA as 0.2g, 0.4g and 0.6g per week by injection, respectively. | 47 |
| Total | 92 |
Baseline characteristics
| Characteristic | Control Group | Experimental Group | Total |
|---|---|---|---|
| Age, Continuous | 30.40 years STANDARD_DEVIATION 13.28 | 31.15 years STANDARD_DEVIATION 13.21 | 30.78 years STANDARD_DEVIATION 13.17 |
| Race/Ethnicity, Customized Chinese Han | 45 participants | 47 participants | 92 participants |
| Region of Enrollment China | 45 participants | 47 participants | 92 participants |
| Sex/Gender, Customized Female | 38 participants | 40 participants | 78 participants |
| Sex/Gender, Customized Male | 7 participants | 7 participants | 14 participants |
| SLE patients | 45 participants | 47 participants | 92 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 47 | 16 / 45 |
| serious Total, serious adverse events | 6 / 47 | 19 / 45 |
Outcome results
Primary
Adverse Reaction (Leucopenia)
The count of white cells \< 4.0 × 10ˆ9/L in SLE patient who received CPA medication was considered as CPA-induced leucopenia.
Time frame: one month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Group | Adverse Reaction (Leucopenia) | 6 participants |
| Control Group | Adverse Reaction (Leucopenia) | 19 participants |
Comparison: Null hypothesis: there is no difference between the control group and experimental group in terms of frequency of leucopenia.(α=0.05） Chi-square test was applied to test the difference. The Chi-square value was 10.08 and the P-value was 0.0015, which indicated that the null hypothesis could be rejected.p-value: <0.0195% CI: [1.76, 14.14]Chi-squared
Secondary
Adverse Reaction ( Infection )
Flu-like symptoms, Upper respiratory tract infection，and the etc.
Time frame: one month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Group | Adverse Reaction ( Infection ) | 8 participants |
| Control Group | Adverse Reaction ( Infection ) | 16 participants |
p-value: <0.0595% CI: [1.01, 7.13]Chi-squared