A Prospective Trial of Enavogliflozin to Evaluate Cardio-renal Outcome in Type 2 Diabetes Mellitus Patients (ENVELOP)

A Prospective, Open, Registry-based Randomized, Controlled, Investigator Initiated Trial of Enavogliflozin(ENVlo) to EvaLuate Cardio-renal Outcome in Type 2 Diabetes Mellitus Patients (ENVELOP Study)

The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor, enavogliflozin, effectively reduces glycated hemoglobin (HbA1c) levels and body weight without increasing the risk of serious adverse events. However, its long-term clinical benefits concerning cardiovascular and renal outcomes have yet to be thoroughly studied. This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults aged 19 or older with type 2 diabetes who have a history of, or are at risk for, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular and renal events. This trial aims to determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with type 2 diabetes and cardiovascular risk factors. It will also clarify role of enavogliflozin in preventing vascular complications in this patient population.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Kidney Diseases; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Enavogliflozin; Drug: Dapagliflozin or Empagliflozin

Detailed Description

The ENVELOP study aims to assess cardiorenal outcomes following enavogliflozin administration compared with dapagliflozin or empagliflozin in Korean patients with type 2 diabetes, representing the first large-scale SGLT2 inhibitor outcome study targeting this population.

• Study Type: Interventional
• Enrollment (Estimated): 2862
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
    • Contact: Bong Soo Cha, MD, PhD; Phone Number: +82-2-2228-1962; Email: bscha@yuhs.ac

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male and female adults aged 19 years and older at screening
2. Subjects diagnosed with T2D at screening
3. Subjects on treatment with or requiring treatment with enavogliflozin, dapagliflozin, or empagliflozin within the scope of label and reimbursement criteria

Exclusion Criteria:

1. Subjects with different types of diabetes mellitus other than T2D
2. Subjects with moderate to severe hepatic impairment
3. Subjects with contraindications to SGLT-2 inhibitors, i.e., kidney function disorders with estimated glomerular filtration (eGFR) <60 mL/min/1.73 m2, end stage renal disease (ESRD), or on dialysis
4. Subjects with major comorbidities
5. Subjects with a history of hypersensitivity to enavogliflozin, dapagliflozin, or empagliflozin and any of its components
6. Pregnant or breastfeeding women

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: Enavogliflozin Group; Subjects will take Enavogliflozin according to the investigator's judgment.	Drug: Enavogliflozin; The dosage and administration method are determined according to the investigator's judgment, considering the drug's approval requirements and the medical condition of the study participants.
Active Comparator: Dapagliflozin, Empagliflozin Group; Subjects will take Dapagliflozin or Empagliflozin according to the investigator's judgment.	Drug: Dapagliflozin or Empagliflozin; The dosage and administration method are determined according to the investigator's judgment, considering the drug's approval requirements and the medical condition of the study participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomization to first onset of cardiorenal composite outcome event	Major adverse cardiovascular events include nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization for unstable angina, hospitalization for heart failure, coronary or peripheral revascularization, and death from any cause. Renal events include a sustained decline in estimated glomerular filtration rate (GFR) calculated by means of the Chronic Kidney Disease Epidemiology Collaboration equation of ≥40% from baseline to <60 mL/min/1.73m2, onset of end-stage kidney disease (dialysis for ≥28 days, kidney transplantation, or an estimated GFR of <15 mL/min/1.73m2), development of macroalbuminuria, and death from renal causes.	6 months, 12 months, 24 months, 36 months and 48 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomization to the first onset of 3-point MACE and proportion of the patients	Time to first event of a composite of key major adverse cardiovascular events (non-fatal MI, non-fatal stroke, and death from cardiovascular causes)	6 months, 12 months, 24 months, 36 months and 48 months
death from any cause	Time to death from any cause	6 months, 12 months, 24 months, 36 months and 48 months
death from cardiovascular causes	Time to death from cardiovascular cause	6 months, 12 months, 24 months, 36 months and 48 months
hospitalization due to unstable angina	Time to first event of hospitalization due to unstable angina	6 months, 12 months, 24 months, 36 months and 48 months
hospitalization due to heart failure	Time to first event of hospitalization due to heart failure	6 months, 12 months, 24 months, 36 months and 48 months
coronary or peripheral revascularization	Time to first event of coronary or peripheral revascularization	6 months, 12 months, 24 months, 36 months and 48 months
major renal events	Time to first event of a composite of major kidney events	6 months, 12 months, 24 months, 36 months and 48 months
progression of macroalbuminuria	Time to development of macroalbuminuria	6 months, 12 months, 24 months, 36 months and 48 months

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2024
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: October 13, 2024
• First Submitted That Met QC Criteria: October 13, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 13, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Empagliflozin
• Other Study ID Numbers: 4-2023-1334

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No