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

NCT ID: NCT05469659

Last Updated: 2022-07-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-22
• Study Completion Date: 2026-10-30

Brief 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).

Detailed 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.

Conditions

T2DM (Type 2 Diabetes Mellitus); Metformin; SGLT2-Inhibitors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tofogliflozin

Group Type: EXPERIMENTAL

Tofogliflozin

Intervention Type: DRUG

Tofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast.

Metformin

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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.

Interventions

Tofogliflozin

Tofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kowa Company, Ltd.

INDUSTRY

Sponsor Role: collaborator

Shinshu University

OTHER

Sponsor Role: lead

Responsible Party

Koichiro Kuwahara

MD, PhD, Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Koichiro Kuwahara, MD, PhD

Role: STUDY_CHAIR

Shinshu University School of Medicine

Locations

Shinshu University

Matsumoto, Nagano, Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Koichiro Kuwahara, MD, PhD

Role: CONTACT

kkuwah@shinshu-u.ac.jp

+81-263-37-3191

Facility Contacts

Koichiro Kuwahara, MD, PhD

Role: primary

kkuwah@shinshu-u.ac.jp

+81-263-37-3191

Masatoshi Minamisawa

Role: backup

nanchan7131@gmail.com

+81-263-37-3191

References

El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.

Reference Type: DERIVED

PMID: 38837240 (View on PubMed)

Other Identifiers

jRCTs031210339

Identifier Type: REGISTRY

Identifier Source: secondary_id

21-02

Identifier Type: -

Identifier Source: org_study_id