A Prospective Study of Cyclophosphamide in Systemic Lupus Erythematosus Treatment

NCT ID: NCT01689350

Last Updated: 2014-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-03-31

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Control Group

The 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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Experimental Group

Genetic: Genotype 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),with initial dose of CPA as 0.2g, 0.4g and 0.6g per week by injection, respectively.

Group Type: EXPERIMENTAL

Genotype Detection

Intervention Type: GENETIC

To Genotype cases in the experimental group and divide them into three groups, including extensive metaboliser (EM), intermediate metaboliser (IM) and poor metaboliser (PM).

Interventions

Genotype 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).

Intervention Type: GENETIC

Eligibility Criteria

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;

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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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Lingyan Chen

Master Graduate Student

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Huang Min, PhD

Role: STUDY_CHAIR

Sun Yat-sen University

Locations

School of Pharmaceutical Sciences Sun Yat-sen University

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

2012ZX09506001-004

Identifier Type: -

Identifier Source: org_study_id