Effect of Dotinurad in Hyperuricemia With Hypertension (DIANA-NEXT)

Effect of Dotinurad in Hyperuricemia With Hypertension: a Randomized Study With Febuxostat (DIANA-NEXT)

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

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Hyperuricemia or Gout
• Intervention / Treatment: Drug: Dotinurad; Drug: Febuxostat

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.

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Koichi Koichi, Pr.,Dr.; Phone Number: +81-952-28-8100; Email: next-diana@clin-med.org

Study Locations

• Japan
  • Saga-ken
    • Saga, Saga-ken, Japan, 840-8502
      • Recruiting
      • Saga University
      • Contact: Atsushi Tanaka; Phone Number: +81-952-34-2364; Email: tanakaa2@cc.saga-u.ac.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dotinurad; Start at 0.5 mg once daily, and then referring to the attached document and the following dosage examples, gradually increase the dose to the maintenance dose (2 mg once daily).	Drug: Dotinurad; Start at 0.5 mg once daily, and then referring to the attached document, gradually increase the dose to the maintenance dose (2 mg once daily).; Other Names: URECE
Active Comparator: Febuxostat; Start at 10 mg once daily, and then referring to the attached document and the following dosage examples, gradually increase the dose to the maintenance dose (40 mg once daily).	Drug: Febuxostat; Start at 10 mg once daily, and then referring to the attached document, gradually increase the dose to the maintenance dose (40 mg once daily).; Other Names: Feburic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CAVI	Change in CAVI at 24 weeks after study drug administration	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CAVI category	Change in CAVI category (<8.0: normal, 8.0 to 9.0: borderline, 9.0 or greater: abnormal) at 24 weeks after study drug administration (key secondary endpoint)	24 weeks
Change in CAVI	Change in CAVI at 12 weeks after study drug administration	12 weeks
Change in CAVI category	Change in CAVI category (<8.0: normal, 8.0 to 9.0: borderline, 9.0 or greater: abnormal) at 12 weeks after study drug administration	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum uric acid levels	Changes in serum uric acid levels at 4, 8, 12 and 24 weeks after study drug administration	4, 8, 12 and 24 weeks
Percentage of patients whose serum uric acid levels reach 6.0 mg/dL or less	Percentage of patients whose serum uric acid levels reach 6.0 mg/dL or less at 4, 8, 12, and 24 weeks after study drug administration	4, 8, 12 and 24 weeks
Change in AI	Change in AI at 24 weeks after study drug administration	24 weeks
Change in %MAP	Change in %MAP at 24 weeks after study drug administration	24 weeks
Change in serum NT-proBNP	Change in serum NT-proBNP at 24 weeks after study drug administration	24 weeks
Change in serum CRP	Change in serum CRP at 24 weeks after study drug administration	24 weeks
Change in serum oxidized LDL	Change in serum oxidized LDL at 24 weeks after study drug administration	24 weeks
Change in urinary albumin-creatinine ratio	Change in urinary albumin-creatinine ratio at 24 weeks after study drug administration	24 weeks
Change in urinary 8-OHdG	Change in urinary 8-OHdG at 24 weeks after study drug administration	24 weeks
Change in urinary NAG	Change in urinary NAG at 24 weeks after study drug administration	24 weeks
Changes in systolic and diastolic blood pressures	Changes in systolic and diastolic blood pressures at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in pulse pressure (systolic blood pressure minus diastolic blood pressure)	Changes in pulse pressure (systolic blood pressure minus diastolic blood pressure) at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in AST	Changes in AST at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in ALT	Changes in ALT at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes inγ-GTP	Changes inγ-GTP at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in HDL-C	Changes in HDL-C at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in LDL-C	Changes in LDL-C at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in TG	Changes in TG at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in WBC (including fractions)	Changes in WBC (including fractions) at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in PLT	Changes in PLT at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in Cr	Changes in Cr at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in eGFR	Changes in eGFR at 12 and 24 weeks after study drug administration	12 and 24 weeks
Changes in FIB-4 index	Changes FIB-4 index at 12 and 24 weeks after study drug administration	12 and 24 weeks
Change in echocardiographic parameters (LVEDV)	Change in LVEDV at 24 weeks after study drug administration	24 weeks
Changes in echocardiographic parameters (LVESV)	Changes in LVESV at 24 weeks after study drug administration	24 weeks
Change in echocardiographic parameters (LVEF)	Change in LVEF at 24 weeks after study drug administration	24 weeks
Change in echocardiographic parameters (septal e')	Change in septal e' at 24 weeks after study drug administration	24 weeks
Change in echocardiographic parameters (lateral e')	Change in lateral e' at 24 weeks after study drug administration	24 weeks
Change in echocardiographic parameters (mitral annular velocity (E))	Change in mitral annular velocity (E) at 24 weeks after study drug administration	24 weeks
Change in echocardiographic parameters (E/e')	Change in E/e' at 24 weeks after study drug administration	24 weeks
Change in echocardiographic parameters (LVMI)	Change in LVMI at 24 weeks after study drug administration	24 weeks
Change in echocardiographic parameters (LAVI)	Change in LAVI at 24 weeks after study drug administration	24 weeks
Adverse events	Adverse events that occurred after study drug administration	24 weeks
Changes in protein levels as determined by proteomics analysis	Changes in protein levels as determined by proteomics analysis(Olink Target 96 Inflammation analysis, Olink Target 96 CVDⅡ analysis, Olink Target 96 CVDⅢ analysis) at 24 weeks after study drug administration	24 weeks

Collaborators and Investigators

• Sponsor: Saga University
• Investigators: Principal Investigator: Koichi Node, Pr.,Dr., Saga University

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: January 30, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 19, 2025

Study Record Updates

• Last Update Posted (Actual): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 7, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Arterial stiffness; Febuxostat; CAVI; Dotinurad
• Additional Relevant MeSH Terms: Crystal Arthropathies; Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Gout; Hypertension; Hyperuricemia; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Febuxostat; dotinurad
• Other Study ID Numbers: 00003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No