Lowering-hyperuricemia Treatment on Cardiovascular Outcomes in Peritoneal Dialysis Patients

Phase 4

• Conditions: Hyperuricemia
• Interventions: Drug: Placebo; Drug: Febuxostat

• Registration Number: NCT03200210
• Lead Sponsor: Sun Yat-sen University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-06-25
• Study First Submitted QC: 2017-06-25
• Study First Posted: 2017-06-27
• Study Start: 2017-07-11
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-20
• Last Update Posted: 2020-10-22
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 548

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment with placebo	Placebo	Same dose and dose adjustment as the intervention arm.
Treatment with Febuxostat	Febuxostat	Febuxostat, starting at dose 20mg/d, once a day. And adjust dose according to serum uric acid at specific visits.

Primary Outcome Measures

Name	Time	Method
Cardiovascular events	3 years	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

Secondary Outcome Measures

Name	Time	Method
All-cause mortality	3 years	To record and calculate the deaths caused by any cause during follow up period
Non-fatal cardiovascular events	3 years	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.
Cardiovascular mortality	3 years	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.

Trial Locations

Locations (1)

The First Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China