Clinical trial NCT06834230: Effect of Dotinurad in Hyperuricemia with Hypertension
Official title: Effect of Dotinurad in Hyperuricemia with Hypertension: a Randomized Study with Febuxostat (DIANA-NEXT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hyperuricemia or Gout
Hypertension
Keywords: Febuxostat
Dotinurad
CAVI
Arterial stiffness
Lead sponsor: Saga University
Sponsor class: OTHER
First posted: 2025-02-19
Enrollment: 360
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Assignment
Primary purpose: TREATMENT

Brief summary: The effect of dotinurad on CAVI (cardio-ankle vascular index) will be compared with that of febuxostat in patients with hyperuricemia complicated by hypertension.

Detailed description: After determining eligibility of patients for whom consent is obtained, all patients who meet the eligibility criteria will be enrolled and randomized to one of two groups: dotinurad or febuxostat. In principle, a baseline (0-week) examination will be conducted within 70days after obtaining consent, followed by 24 weeks of observation and examination. During the observation period, no changes or additions to the dosage or administration of drugs other than the study drug will be made in principle, but changes or additions will be permitted under the overall clinical judgment of the physician in charge according to the medical conditions of the study participants.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 20 years or older at the time of consent (regardless of gender)
2. Patients with hyperuricemia with serum uric acid level \>7.0 mg/dL who have not received any urate lowering drug within 27 days prior to obtaining consent, or patients who were receiving urate lowering drugs at the time of obtaining consent but have been off the drugs for more than 27 days
3. Hypertensive patients who meet the definition of hypertension in the latest Hypertension Treatment Guidelines of the Japanese Society of Hypertension and whose treatment for hypertension (with or without drug therapy) has not changed within 4 weeks prior to eligibility determination
4. Patients who have given written consent to participate in this study

Exclusion Criteria:

1. Patients with unsettled gout after acute gouty arthritis
2. Patients currently suffering from urinary tract stones
3. Patients with known secondary hyperuricemia who have Lesch-Nyhan syndrome, hyperphosphoribosyl pyrophosphate synthase, congenital myogenic hyperuricemia, hematopoietic tumors (acute leukemia, malignant lymphoma, myeloproliferative disorders, myelodysplastic syndrome), solid tumors (breast cancer, seminoma, sarcoma, Wilms' tumor, small cell lung cancer), non-neoplastic diseases (psoriasis vulgaris, secondary polycythemia vera, hemolytic anemia), tumor melting syndrome, rhabdomyolysis, hypothyroidism, polycystic kidney disease, lead poisoning/lead nephropathy, Down syndrome, familial juvenile gout nephropathy, hyperlactatemia, or type 1 glycogenic disease
4. Patients with hypertensive emergencies and urgency
5. Patients with active malignancies
6. Patients with severe hepatic dysfunction
7. Patients with severe renal dysfunction with oliguria or anuria
8. Pregnant, possibly pregnant, or lactating patients
9. Patients with a history of hypersensitivity to the components of dotinurad and febuxostat
10. Patients receiving mercaptopurine hydrate or azathioprine
11. Other patients deemed inappropriate for this study by the investigator

Primary outcomes:
measure: Change in CAVI
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in CAVI category
timeFrame: 24 weeks
measure: Change in CAVI
timeFrame: 12 weeks
measure: Change in CAVI category
timeFrame: 12 weeks
Other outcomes:
measure: Changes in serum uric acid levels
timeFrame: 4, 8, 12 and 24 weeks
measure: Percentage of patients whose serum uric acid levels reach 6.0 mg/dL or less
timeFrame: 4, 8, 12 and 24 weeks
measure: Change in AI
timeFrame: 24 weeks
measure: Change in %MAP
timeFrame: 24 weeks
measure: Change in serum NT-proBNP
timeFrame: 24 weeks
measure: Change in serum CRP
timeFrame: 24 weeks
measure: Change in serum oxidized LDL
timeFrame: 24 weeks
measure: Change in urinary albumin-creatinine ratio
timeFrame: 24 weeks
measure: Change in urinary 8-OHdG
timeFrame: 24 weeks
measure: Change in urinary NAG
timeFrame: 24 weeks
measure: Changes in systolic and diastolic blood pressures
timeFrame: 12 and 24 weeks
measure: Changes in pulse pressure (systolic blood pressure minus diastolic blood pressure)
timeFrame: 12 and 24 weeks
measure: Changes in AST
timeFrame: 12 and 24 weeks
measure: Changes in ALT
timeFrame: 12 and 24 weeks
measure: Changes inγ-GTP
timeFrame: 12 and 24 weeks
measure: Changes in HDL-C
timeFrame: 12 and 24 weeks
measure: Changes in LDL-C
timeFrame: 12 and 24 weeks
measure: Changes in TG
timeFrame: 12 and 24 weeks
measure: Changes in WBC (including fractions)
timeFrame: 12 and 24 weeks
measure: Changes in PLT
timeFrame: 12 and 24 weeks
measure: Changes in Cr
timeFrame: 12 and 24 weeks
measure: Changes in eGFR
timeFrame: 12 and 24 weeks
measure: Changes in FIB-4 index
timeFrame: 12 and 24 weeks
measure: Change in echocardiographic parameters (LVEDV)
timeFrame: 24 weeks
measure: Changes in echocardiographic parameters (LVESV)
timeFrame: 24 weeks
measure: Change in echocardiographic parameters (LVEF)
timeFrame: 24 weeks
measure: Change in echocardiographic parameters (septal e')
timeFrame: 24 weeks
measure: Change in echocardiographic parameters (lateral e')
timeFrame: 24 weeks
measure: Change in echocardiographic parameters (mitral annular velocity (E))
timeFrame: 24 weeks
measure: Change in echocardiographic parameters (E/e')
timeFrame: 24 weeks
measure: Change in echocardiographic parameters (LVMI)
timeFrame: 24 weeks
measure: Change in echocardiographic parameters (LAVI)
timeFrame: 24 weeks
measure: Changes in protein levels as determined by proteomics analysis
timeFrame: 24 weeks
measure: Adverse events
timeFrame: 24 weeks
Locations:
city: Saga
country: Japan
facility: Saga University Hospital
Study officials:
affiliation: Saga University Hospital
name: Koichi Node, Pr.,Dr.
role: PRINCIPAL_INVESTIGATOR
References: