Effect of Tofogliflozin on UACR Compared to Metformin Hydrochloride in Diabetic Kidney Disease (TRUTH-DKD)

Metformin Clinical Trial

— TRUTH-DKD  

Official title:

Effect of Tofogliflozin on Urine Albumin-to-Creatinine Ratio Compared to Metformin Hydrochloride in Diabetic Kidney Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05469659
• Other study ID #: 21-02
• Secondary ID: jRCTs031210339
• Status: Recruiting
• Phase: Phase 2
• Start date: September 22, 2021
• Est. completion date: October 30, 2026

Study information

• Verified date: July 2022
• Source: Shinshu University
• Contact: Koichiro Kuwahara, MD, PhD
• Phone: +81-263-37-3191
• Email: kkuwah[@]shinshu-u.ac.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multicenter, randomized, open-label, controlled study will assess the efficacy of the SGLT2 inhibitor tofogliflozin on Urine Albumin-to-Creatinine Ratio (UACR) compared to metformin in patients with type 2 diabetes with chronic kidney disease (CKD).

Description:

Eligible participants will be randomly assigned (1:1) to tofogliflozin or metformin with stratification based on UACR (<300 mg/gCr，≧300mg/gCr), an estimated glomerular filtration rate (eGFR) (<60mL/min/1.73m2, ≧60 mL/min/1.73m2), and age (<65 years old, ≧65 years old). The primary end point is change in urine albumin-to-creatinine ratio (UACR) from baseline after 52 weeks treatment. Changes in eGFR, HbA1c, body weight, systolic blood pressure, diastolic blood pressure, total serum proteins, serum albumin, uric acid, hematocrit, hemoglobin, red blood cell count, pulse rate, triglyceride, low-density lipoprotein, high-density lipoprotein and albuminuria class transition rate will also be evaluated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: October 30, 2026
• Est. primary completion date: October 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Type 2 diabetic patients
• Patients aged 20 years or older at the time of obtaining consent
• Patients with HbA1c 6.5 or more and 9.0% or less within 13 weeks before obtaining consent (evaluated by test values after 4 weeks or more without taking SGLT2 inhibitor / metformin)
• Patients who have been judged by their doctor to need a diabetic drug when they are first seen, or who have already taken a diabetic drug and have decided that it is necessary to add one diabetic drug.
• Patients who have been receiving RAS inhibitors (ARB, ARNI, ACE inhibitors, direct renin inhibitors) for 4 weeks or longer
• Patients with eGFR of 30 or more (mL / min / 1.73m2) within 13 weeks before obtaining consent (evaluated by test values after 4 weeks or more without taking SGLT2 inhibitor / metformin)
• Patients with urinary albumin / creatinine ratio (UACR) of 30 or more and less than 2000 (mg / gCr) (4 weeks or more without taking SGLT2 inhibitor / metformin) within 13 weeks before obtaining consent Evaluate by inspection value)
• Patients for whom written consent was obtained based on the patient's free will after receiving sufficient explanation for participation in this study

Exclusion Criteria:

• Patients receiving treatment with SGLT2 inhibitor or metformin within 13 weeks before obtaining consent
• Dialysis patient
• Patients with a history of severe hypoglycemia
• Patients with hypersensitivity to SGLT2 inhibitor or metformin
• Pregnant women, lactating patients, and patients who wish to raise children
• Patients with BMI of 35 kg / m2 or more based on the latest measured values within 13 weeks before obtaining consent
• Patients who are contraindicated for the study drug
• Other patients who the attending physician deems inappropriate as a subject

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Kidney Diseases
• Metformin
• T2DM (Type 2 Diabetes Mellitus)

Intervention

Drug:
• Tofogliflozin
Tofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast.
• Metformin
Metformin is started at 500 mg daily and orally administered in 2 to 3 divided doses immediately before or after meals. The dose during the maintenance period is determined by observing the effect, but is usually 750 to 1,500 mg daily. Metformin is orally administered for 104 weeks throughout post-start period. The dose may be adjusted according to the patient's condition, but the maximum daily dose should be 2,250 mg.

Locations

Country	Name	City	State
Japan	Shinshu University	Matsumoto	Nagano

Sponsors (2)

Lead Sponsor	Collaborator
Shinshu University	Kowa Company, Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urine albumin-to-creatinine ratio (UACR)	Change from baseline in urine albumin-to-creatinine ratio (UACR) after 52 weeks treatment.	Up to 52 weeks
Secondary	Urine albumin-to-creatinine ratio (UACR)	Change from baseline in urine albumin-to-creatinine ratio (UACR) after 26 and 104 weeks treatment.	Up to 26 and 104 weeks
Secondary	Urine albumin-to-creatinine ratio (UACR)	Change rates from baseline in urine albumin-to-creatinine ratio (UACR) after 26, 52 and 104weeks treatment.	Up to 26, 52 and 104 weeks
Secondary	Change slope in eGFR	Change slope in eGFR	Up to 52 and 104 weeks
Secondary	HbA1c	Change in HbA1c	Up to 52 and 104 weeks
Secondary	Body weight	Changes in body weight	Up to 52 and 104 weeks
Secondary	Systolic / diastolic blood pressure	Changes in systolic / diastolic blood pressure	Up to 52 and 104 weeks
Secondary	Total serum proteins	Changes in total serum proteins	Up to 52 and 104 weeks
Secondary	Serum albumin	Changes in serum albumin	Up to 52 and 104 weeks
Secondary	Uric acid	Changes in uric acid	Up to 52 and 104 weeks
Secondary	Hematocrit	Changes in hematocrit	Up to 52 and 104 weeks
Secondary	Hemoglobin	Changes in hemoglobin	Up to 52 and 104 weeks
Secondary	Red blood cell count	Changes in red blood cell count	Up to 52 and 104 weeks
Secondary	Pulse rate	Changes in pulse rate	Up to 52 and 104 weeks
Secondary	Triglyceride	Changes in triglyceride	Up to 52 and 104 weeks
Secondary	Low-density lipoprotein	Changes in low-density lipoprotein	Up to 52 and 104 weeks
Secondary	High-density lipoprotein	Changes in high-density lipoprotein	Up to 52 and 104 weeks
Secondary	Albuminuria class	Transition of albuminuria class	Up to 104 weeks