UMIN-ICDS Clinical Trial

Public title

A clinical study comparing the renal effects of dotinurad and febuxostat in patients with chronic kidney disease and hyperuricemia

Acronym

Dotinurad vs Febuxostat Evaluation for Nephropathy Study (Efficacy)

Scientific Title

Effect of Mechanistic Differences in Urate-Lowering Therapies on Chronic Kidney Disease Progression: An Open-Label Randomized Controlled Trial

Scientific Title:Acronym

ULT-MEC Trial (Urate-Lowering Therapy Mechanistic Comparison Trial)

Region

Japan

Condition

hyperuricemia

Classification by specialty

Nephrology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

This study aims to compare and verify the renoprotective effects (assessed by eGFR slope) of dotinurad (a SURI) versus febuxostat (an XOI) in patients with stage 3 or 4 CKD and asymptomatic hyperuricemia.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Annual eGFR slope over the 24-month (2-year) period after treatment initiation

Key secondary outcomes

Incidence of clinical events: All-cause mortality, renal events (defined as a <30% decline in eGFR from baseline or progression to End-Stage Kidney Disease [ESKD]), cardiovascular events, and hospitalization events.
Achievement rate of target serum uric acid levels (<6.0 mg/dL).
Changes in urinary tubular injury markers from baseline: Short-term changes at 1 month and long-term changes over 2 years.
Changes in safety parameters: Complete blood count, liver function (AST, ALT), kidney function (BUN, Cr, eGFR), electrolytes (Na, K, Cl), and inflammatory markers (CRP).Changes in comorbidity management indices: HbA1c or glycated albumin in patients with diabetes; TC, TG, LDL-C, and HDL-C in patients with dyslipidemia or cardiovascular complications.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Dotinurad group:Oral administration of dotinurad, a selective urate reabsorption inhibitor (SURI). The duration of administration is 24 months (2 years). Dosage and administration are adjusted according to the package insert and the attending physician's clinical judgment, targeting a serum uric acid level of <6.0 mg/dL. In principle, the drug is used within the standard dosage range (starting dose 0.5 mg/day, maintenance dose 1-4 mg/day).

Interventions/Control_2

Febuxostat group:Oral administration of febuxostat, a xanthine oxidase inhibitor (XOI). The duration of administration is 24 months (2 years). Dosage and administration are adjusted according to the package insert and the attending physician's clinical judgment, targeting a serum uric acid level of <6.0 mg/dL. In principle, the drug is used within the standard dosage range (starting dose 10 mg/day, maintenance dose 10-60 mg/day).

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients aged 18 years or older at the time of informed consent.
Patients with Chronic Kidney Disease (CKD) stage 3 or 4 (eGFR >15 and <60 mL/min/1.73m2 within 12 weeks prior to registration).
Patients with asymptomatic hyperuricemia (serum uric acid level >7.0 mg/dL recorded at least once within 12 weeks prior to registration).
Patients who have received a stable dose of Angiotensin-Converting Enzyme (ACE) inhibitor or Angiotensin II Receptor Blocker (ARB) for at least 1 month prior to registration, if indicated and tolerated. (Patients for whom these drugs are medically contraindicated or not indicated are eligible without their use).

Key exclusion criteria

Patients with difficulty in providing informed consent or adhering to medication (e.g., severe dementia visiting alone, significant poor compliance).
Patients diagnosed with symptomatic gout, or those who have taken urate-lowering drugs within 12 weeks prior to study initiation.
Patients who have initiated or changed the dose of RAS inhibitors or SGLT2 inhibitors within 4 weeks prior to registration.
Patients undergoing treatment for malignancy (excluding carcinoma in situ).
Patients undergoing dialysis, those who have received a kidney transplant, or those scheduled for kidney transplantation within 6 months.
Patients participating in other interventional studies or clinical trials.
Patients who are pregnant, breastfeeding, or possibly pregnant.
Patients with a history of hypersensitivity to febuxostat or dotinurad.
Patients receiving mercaptopurine hydrate or azathioprine (contraindicated with febuxostat).
Patients undergoing treatment for urinary calculi (contraindication for urate excretion promoters).
Patients with active liver disease defined as AST or ALT >3 times the upper limit of normal.
Patients with polycystic kidney disease.
Patients who developed acute kidney injury (AKI) within 3 months prior to consent and have not recovered.
Patients with urinary protein-to-creatinine ratio (UPCR) >5 g/gCr or urinary albumin-to-creatinine ratio (UACR) >3000 mg/gCr in the latest spot urine test prior to consent.
Other patients judged inappropriate by the investigator from the viewpoint of study conduct or ethics.

Target sample size

200

Name of lead principal investigator

1st name	Hikaru
Middle name
Last name	Uematsu

Organization

Toho University Ohashi Medical Center

Division name

Department of Nephrology

Zip code

153-8515

Address

2-22-36 Ohashi, Meguro-ku, Tokyo

TEL

03-3468-1251

Email

hikaru.uematsu@med.toho-u.ac.jp

Name of contact person

1st name	Hikaru
Middle name
Last name	Uematsu

Organization

Toho University Ohashi Medical Center

Division name

Department of Nephrology

Zip code

153-8515

Address

2-22-36 Ohashi, Meguro-ku, Tokyo

TEL

03-3468-1251

Homepage URL

Email

toho-nephron.rct@ml.toho-u.jp

Institute

Toho University

Institute

Department

Personal name

Hikaru Uematsu

Organization

Toho University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ethics Committee of the Faculty of Medicine, Toho University

Address

5-21-16 Omori-nishi, Ota-ku, Tokyo

Tel

03-3762-4151

Email

med.rinri@ext.toho-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2025

Year

11

Month

30

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2025

Year

11

Month

30

Day

Date of IRB

Anticipated trial start date

2025

Year

12

Month

01

Day

Last follow-up date

2028

Year

06

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2025

Year

11

Month

21

Day

Last modified on

2025

Year

11

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000068441