Lowering-hyperuricemia Treatment on Cardiovascular Outcomes in Peritoneal Dialysis Patients

Study Overview
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Brief Summary
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The investigators will enroll continuous ambulatory peritoneal dialysis (CAPD) patients with hyperuricemia and randomly divide them into two groups, treated with Febuxostat and placebo respectively. After 3 years of following up, cardiovascular events, all cause mortality, cardiovascular mortality and non-fatal cardiovascular events are collected and recorded. The difference of cardiovascular events, all cause mortality and non-fatal cardiovascular event rate will be analyzed.

Detailed Description
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The investigators anticipate enrolling 548 CAPD patients who have hyperuricemia in 21 centers and randomly allocate them into Febuxostat treatment group and placebo group. This study is double-blinded and will be followed up for 3 years. The primary endpoint is cardiovascular events, secondary endpoints are all-cause mortality, cardiovascular mortality and non-fatal cardiovascular events separately. All the endpoints will be collected, as well as other outcomes, such as blood pressure and dialysis dose and so on. The outcomes will be analyzed using statistics software.

Official Title
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Lowering-hyperuricemia Treatment on Cardiovascular Outcomes in Peritoneal Dialysis Patients: A Prospective, Multicenter, Double-Blinded, Randomized Controlled Trial

Conditions
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Hyperuricemia

Intervention / Treatment
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* Drug: Febuxostat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Subjects who are able to understand and have voluntarily signed the informed consent form (ICF) 18-70 years old at the time of randomization Subjects on PD for more than 3 months. Subjects have hyperuricemia, women: 6mg/dl(360μmol/L) <serum uric acid (sUA)<12mg/dl(720μmol/L); men: 7mg/dl(420μmol/L)<sUA<12mg/dl(720μmol/L). Exclusion Criteria: 1.Subjects has history of gout Subjects who have a myocardial infarction, unstable angina,cardiovascular reconstructive surgery (such as a stent or bypass surgery), cerebrovascular accident 12 weeks prior to randomization, or plan cardiovascular reconstructive surgery during the trial Subjects who have New York stage IV heart failure occurs 4 weeks prior to the screening Subjects who have previously received renal transplantation and are currently prescribed immunosuppressive therapy Subjects who have severe liver disease, such as acute hepatitis, chronic active hepatitis, cirrhosis Subjects who have alanine aminotransferase (ALT) greater than 2 folds of the upper limited of normal or total bilirubin greater than 1.5 folds of upper limited of normal Subjects who have severe infections 4 weeks prior to the screening, such as pneumonia and peritoneal dialysis-related peritonitis; Subjects who have a major surgery 12 weeks prior to screening or not yet fully recovered from the surgery Subjects who have a malignancy Subjects who report a history of illicit drug use or a regular or daily alcohol consumption of≥4 alcoholic drinks per day in the 2 years before Screening Subjects who are allergic to Febuxostat Subjects who are enrolled in other clinical studies within 4 weeks or currently at randomization Subjects who are currently taking mercaptopurine, azathioprine, vidarabine, didanosine Subjects who are taking losartan, fenofibrate, thiazide diuretics or loop diuretics within 4 weeks at randomization Subjects who require long-term use of steroids (prednisone <30mg / d, or equivalent amount of other steroids and the use of <2 weeks can be enrolled) Subjects who require long-term use of salicylic acid drugs except low-dose aspirin Fertility, lactation patients unwilling or unable to contraception

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with Febuxostat<br>Febuxostat, starting at dose 20mg/d, once a day. And adjust dose according to serum uric acid at specific visits. | Drug: Febuxostat<br>* Febuxostat tablets would be given to patients at dose of 20mg/d, once a day, and dose would be adjusted according to serum uric acid at specific visits.<br>* Other names: Febuxostat Tablets;|
| Placebo Comparator: Treatment with placebo<br>Same dose and dose adjustment as the intervention arm. | Drug: Placebo<br>* Pills manufactured to mimic Febuxostat tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular events | Cardiovascular events compose of cardiovascular mortality and non-fatal cardiovascular events, cardiovascular mortality includes acute myocardial infarction, fatal arrhythmia, sudden death, cardiomyopathy, heart failure, and stroke; non-fatal cardiovascular events includes non-fatal acute myocardial infarction, hospital admission of heart failure, unstable angina, atherosclerotic disease needed hospitalization (including aneurysm, arterial dissection, arteriosclerosis occlusion), non-fatal stroke, transient ischaemic attack or lower limb ischaemia | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | To record and calculate the deaths caused by any cause during follow up period | 3 years | 
| Cardiovascular mortality | To record and calculate the deaths cardiovascular mortality includes acute myocardial infarction, fatal arrhythmia, sudden death, cardiomyopathy, heart failure, and stroke during follow up period. | 3 years | 
| Non-fatal cardiovascular events | To record and calculate the non-fatal cardiovascular events including non-fatal acute myocardial infarction, hospital admission of heart failure, unstable angina, atherosclerotic disease needed hospitalization (including aneurysm, arterial dissection, arteriosclerosis occlusion), non-fatal stroke, transient ischaemic attack or lower limb ischaemia during follow up period. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment, Continuous Ambulatory Peritoneal Dialysis (CAPD), Hyperuricemia, Cardiovascular events