Rasburicase Treatment in Chronic Gouty Arthritis

Study Overview
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Brief Summary
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The study will establish efficacy and safety of rasburicase in chronic gouty arthritis

Detailed Description
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The study hypothesis is that the proportion of patients who achieved the primary endpoint after 12 weeks of treatment with rasburicase combined with oral urate-lowering therapy is superior to 12 weeks of treatment with oral urate-lowering therapy.

Official Title
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Efficacy and Safety of Rasburicase in the Treatment of Chronic Gouty Arthritis: A Multicenter Randomized Controlled Study

Conditions
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Chronic Gout

Intervention / Treatment
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* Drug: Rasburicase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed, able to understand and comply with the requirements of the study; Male and female patients 18 to 70 years of age; Fulfill the ACR/EULAR 2015 gout classification criteria; Tophi detected by physical examination; Serum urate>300μmol/L (5mg/dl) after one-month maximum dose of urate-lowering therapy (allopurinol 600mg/d or febuxostat 80mg/d in combination with benzbromarone 100mg/d) unless intolerable OR no reduction in size of tophi after serum urate<300μmol/L (5mg/dl) for six month; Exclusion Criteria: Pregnant women, lactating women, and men or women who have recently prepared for pregnancy; Abnormal liver function with AST, ALT, and GGT >3 times ULN; Blood WBC<4.0×10^9/L, and/or hemoglobin <90g/L, and/or platelets;<100×10^9/L; or other hematologic disorders; eGFR<15 ml/min; Receive following medications: azathioprine, mercaptopurine, cyclosporine, pyrazinamide, ethambutol and sulfamethoxazole Psychiatric disorders, history of alcoholism, drug or other substance abuse Immunodeficiency diseases, uncontrolled infection, etc; Sericosis, glucose-6-phosphate dehydrogenase activity deficiency Allergy to biological agents and chronic active urticaria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group A<br>Rasburicase treatment at week 1, 4 and 8 with stable dose oral urate-lowering therapy for 24 weeks. | Drug: Rasburicase<br>* Rasburicase 1.5 mg/day for 3 consecutive days at scheduled times.<br>|
| Other: Group B<br>Rasburicase treatment at week 12, 16 and 20 with stable dose oral urate-lowering therapy for 24 weeks. | Drug: Rasburicase<br>* Rasburicase 1.5 mg/day for 3 consecutive days at scheduled times.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monosodium urate crystal volume change evaluated by dual energy CT | Dual energy CT at baseline, week 12 and week 24 | Baseline to week 12 and week 12 to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tophus volume change evaluated by physical examination |  | Baseline to week 12 and week 12 to week 24 | 
| The percentage of patients who have at least one tophi disappeared |  | Baseline to week 12 and week 12 to week 24 | 
| The percentage of patients who had achieved serum urate concentrations less than 300 μmol/L (5mg/dl) after 3 months of rasburicase treatment |  | Baseline to week 12 and week 12 to week 24 | 
| Number of gout flare |  | Baseline to week 12 and week 12 to week 24 | 
| Change of patient global assessment | The patient global assessment is given as a single question, scored from 0-10, with higher numbers representing worse perceived disease activity or overall health. | Baseline to week 12 and week 12 to week 24 | 
| Change of physician global assessment | The physician global assessment is given as a single question, scored from 0-10, with higher numbers representing worse perceived disease activity or overall health. | Baseline to week 12 and week 12 to week 24 | 
| Change of Visual Analog Scale (VAS) for Pain in gout flare | Visual Analog for Pain consists of a horizontal line, usually 100mm in length. The left end of the line signifies no pain while the right end signifies the worst possible pain. | Baseline to week 12 and week 12 to week 24 | 
| Change of global functional status | The criteria are as follows: class I = able to perform usual activities of daily living (self-care, vocational, and avocational); class II = able to perform usual self-care and vocational activities, but limited in avocational activities; class III = able to perform usual self-care activities but limited in vocational and avocational activities; class IV = limited in ability to perform usual self-care, vocational, and avocational activities. | Baseline to week 12 and week 12 to week 24 | 
| Change of Short Form 12 health survey score |  | Baseline to week 12 and week 12 to week 24 | 
| Change of Tophus Impact Questionnaire (TIQ)-20 score |  | Baseline to week 12 and week 12 to week 24 | 
| Adverse event |  | Baseline to week 12 and week 12 to week 24 | 
| Severe adverse event |  | Baseline to week 12 and week 12 to week 24 | 
| Number of patients who have positive anti-rasburicase antibodies |  | Baseline to week 12 and week 12 to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic gouty arthritis, Rasburicase