Hypertension, Hyperuricemia or Gout
Conditions
Keywords
Febuxostat, Dotinurad, CAVI, Arterial stiffness
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.
Interventions
DRUGDotinurad
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).
DRUGFebuxostat
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).
Sponsors
Saga University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Assignment
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CAVI | 24 weeks | Change in CAVI at 24 weeks after study drug administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CAVI category | 24 weeks | 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) |
| Change in CAVI | 12 weeks | Change in CAVI at 12 weeks after study drug administration |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in AI | 24 weeks | Change in AI at 24 weeks after study drug administration |
| Change in %MAP | 24 weeks | Change in %MAP at 24 weeks after study drug administration |
| Change in serum NT-proBNP | 24 weeks | Change in serum NT-proBNP at 24 weeks after study drug administration |
| Change in serum CRP | 24 weeks | Change in serum CRP at 24 weeks after study drug administration |
| Change in urinary albumin-creatinine ratio | 24 weeks | Change in urinary albumin-creatinine ratio at 24 weeks after study drug administration |
| Change in urinary 8-OHdG | 24 weeks | Change in urinary 8-OHdG at 24 weeks after study drug administration |
| Change in urinary NAG | 24 weeks | Change in urinary NAG at 24 weeks after study drug administration |
| Changes in systolic and diastolic blood pressures | 12 and 24 weeks | Changes in systolic and diastolic blood pressures at 12 and 24 weeks after study drug administration |
| Changes in pulse pressure (systolic blood pressure minus diastolic blood pressure) | 12 and 24 weeks | Changes in pulse pressure (systolic blood pressure minus diastolic blood pressure) at 12 and 24 weeks after study drug administration |
| Changes in AST | 12 and 24 weeks | Changes in AST at 12 and 24 weeks after study drug administration |
| Changes in ALT | 12 and 24 weeks | Changes in ALT at 12 and 24 weeks after study drug administration |
| Changes inγ-GTP | 12 and 24 weeks | Changes inγ-GTP at 12 and 24 weeks after study drug administration |
| Changes in HDL-C | 12 and 24 weeks | Changes in HDL-C at 12 and 24 weeks after study drug administration |
| Changes in LDL-C | 12 and 24 weeks | Changes in LDL-C at 12 and 24 weeks after study drug administration |
| Changes in TG | 12 and 24 weeks | Changes in TG at 12 and 24 weeks after study drug administration |
| Change in serum oxidized LDL | 24 weeks | Change in serum oxidized LDL at 24 weeks after study drug administration |
| Changes in PLT | 12 and 24 weeks | Changes in PLT at 12 and 24 weeks after study drug administration |
| Changes in Cr | 12 and 24 weeks | Changes in Cr at 12 and 24 weeks after study drug administration |
| Changes in eGFR | 12 and 24 weeks | Changes in eGFR at 12 and 24 weeks after study drug administration |
| Changes in FIB-4 index | 12 and 24 weeks | Changes FIB-4 index at 12 and 24 weeks after study drug administration |
| Change in echocardiographic parameters (LVEDV) | 24 weeks | Change in LVEDV at 24 weeks after study drug administration |
| Changes in echocardiographic parameters (LVESV) | 24 weeks | Changes in LVESV at 24 weeks after study drug administration |
| Change in echocardiographic parameters (LVEF) | 24 weeks | Change in LVEF at 24 weeks after study drug administration |
| Change in echocardiographic parameters (septal e') | 24 weeks | Change in septal e' at 24 weeks after study drug administration |
| Change in echocardiographic parameters (lateral e') | 24 weeks | Change in lateral e' at 24 weeks after study drug administration |
| Change in echocardiographic parameters (mitral annular velocity (E)) | 24 weeks | Change in mitral annular velocity (E) at 24 weeks after study drug administration |
| Change in echocardiographic parameters (E/e') | 24 weeks | Change in E/e' at 24 weeks after study drug administration |
| Change in echocardiographic parameters (LVMI) | 24 weeks | Change in LVMI at 24 weeks after study drug administration |
| Change in echocardiographic parameters (LAVI) | 24 weeks | Change in LAVI at 24 weeks after study drug administration |
| Changes in protein levels as determined by proteomics analysis | 24 weeks | 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 |
| Adverse events | 24 weeks | Adverse events that occurred after study drug administration |
| Changes in WBC (including fractions) | 12 and 24 weeks | Changes in WBC (including fractions) at 12 and 24 weeks after study drug administration |
| Changes in serum uric acid levels | 4, 8, 12 and 24 weeks | Changes in serum uric acid levels at 4, 8, 12 and 24 weeks after study drug administration |
| Percentage of patients whose serum uric acid levels reach 6.0 mg/dL or less | 4, 8, 12 and 24 weeks | 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 |
Countries
Japan
Contacts
Primary ContactKoichi Koichi, Pr.,Dr.
Outcome results
None listed