Lowering-hyperuricemia Treatment on Cardiovascular Outcomes in Peritoneal Dialysis Patients (LUMINA)

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

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.

Study Overview

• Status: Unknown
• Conditions: Hyperuricemia
• Intervention / Treatment: Drug: Febuxostat; Drug: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 548
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xueqing Yu, MD, PhD; Phone Number: 8620-87766335; Email: yuxq@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-Sen University
      • Contact: Yu
      • Contact: Xueqing Yu, M.D. & Ph.D; Phone Number: 8620-8776633; Email: yuxq@mail.sysu.edu.cn
      • Principal Investigator: Xueqing Yu, M.D. & Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with Febuxostat; Febuxostat, starting at dose 20mg/d, once a day. And adjust dose according to serum uric acid at specific visits.	Drug: Febuxostat; 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.; Other Names: Febuxostat Tablets
Placebo Comparator: Treatment with placebo; Same dose and dose adjustment as the intervention arm.	Drug: Placebo; Pills manufactured to mimic Febuxostat tablets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Xueqing Yu, MD, PhD, First Affiliated Hospital, Sun Yat-Sen University

Publications and helpful links

General Publications

• Chen W, Huang N, Mao H, Yang X, Zhou Q, Jiang L, Ding J, Feng Q, Yu X. Rationale and design for Lowering-hyperUricaemia treatment on cardiovascular outcoMes In peritoNeal diAlysis patients: a prospective, multicentre, double-blind, randomised controlled trial (LUMINA). BMJ Open. 2020 Oct 10;10(10):e037842. doi: 10.1136/bmjopen-2020-037842.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2017
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: June 25, 2017
• First Submitted That Met QC Criteria: June 25, 2017
• First Posted (Actual): June 27, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Treatment; Hyperuricemia; Cardiovascular events; Continuous Ambulatory Peritoneal Dialysis (CAPD)
• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia; Antirheumatic Agents; Gout Suppressants; Febuxostat
• Other Study ID Numbers: Lumina

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No