Comparison Between the Efficacy of SGLT2 Inhibitor Therapy Versus ACE Inhibitor in the Treatment of Diabetic Kidney Disease

NCT05373004 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: 54520
• Study Type: interventional
• Target: 212
• Locations: 0 countries
• Sites: N/A

Brief Summary

Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease worldwide. Diabetic kidney disease (DKD) is a clinical diagnosis based upon the presence of reduced glomerular filtration rate (GFR) and/or increased urinary albumin excretion (UACR) in diabetes. The inhibition of the renin-angiotensin system (RAS) has been identified as the cornerstone in the management of DKD for decades. Recently, more evidence supports the use of Sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of DKD. They were associated with slower progression of renal disease and lower rates of clinically relevant kidney events. Those studies confirmed the SGLT2i efficacy in kidney protection and showed that their addition to angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBS) will be more effective than using ACEi or ARBS alone. It is unclear whether SGLT2i is used as a first-line instead of ACEi or ARB, and to what extent it will be effective in managing DKD compared to the proven effect of ACEi/ARBs alone. This study provides a unique opportunity to address this gap in the literature. The aim of this study is to compare, head to head, the renal performance of ACEi (standard of care) versus SGLT2 in diabetic patients who have evidence of deteriorating renal function evidenced by either the reduction of e GFR or increased UACR. Scientific hypotheses: Null hypothesis: after one year, the mean change of the e GFR in the enalapril group - Mean change of the e GFR in the empagliflozin group \> or = 5 ml/min/1.73m2 Alternative hypothesis: after one year, the mean change of the e GFR in the enalapril group - Mean change of the e GFR in the empagliflozin group \< 5 ml/min/1.73m2

Conditions

Diabetic Nephropathy Type 2

Keywords

diabetic kidney disease (DKD); SGLT2 inhibitors; ACE inhibitors

Outcome Measures

Primary Outcomes (1)

• estimated glomerular filtration rate

  eGFR rate (determined by the Modification of Diet in Renal Disease \[MDRD\] equation) in ml/min/1.73m2

  one year

Secondary Outcomes (1)

• the change in Urine Albumin Creatinine Ratio (UACR)

  One year

Other Outcomes (3)

• blood pressure

  One year

• the serum creatinine level

  one year

• the rates of clinical events (myocardial infarction, ESRD, congestive heart failure, and stroke)

  one year

Study Arms (2)

Empagliflozin 25 mg arm (SGLT2 inhibitor)

EXPERIMENTAL

empagliflozin 10 mg once daily plus a placebo enalapril 10 mg tab, along with conventional antihypertensive (for hypertension patients) \& glycemic control therapies (if present). After four weeks, the dose of empagliflozin will be increased to 25 mg once (with Enalapril 20 mg placebo) daily throughout the study for one year.

Drug: Empagliflozin 25 MG

Enalapril 20 mg arm (ACE inhibitor)

ACTIVE COMPARATOR

enalapril 10 mg tab once daily plus a placebo empagliflozin 10 mg tab, along with conventional antihypertensive (for hypertension patients) \& glycemic control therapies (if present). After four weeks, the dose of enalapril will be increased to 20 mg once (with Empagliflozin 25 mg placebo) daily throughout the study for one year.

Drug: Enalapril Maleate 20 mg

Interventions

Empagliflozin 25 MG DRUG

It is the experimental drug in this trial. this drug has an approved efficacy in delaying kidney deterioration based on the results of (the EMPA-REG OUTCOME) trial. it is also recommended based on the ADA/EASD 2019 consensus, as the SGLT2 inhibitors are recommended in patients with type 2 diabetes in patients with CKD to prevent the progression of CKD. However, the previous trials where always add it to a patient already on an ACE inhibitor (in most cases). In this trial, it will be compared head to head with the gold standard treatment of CKD which is Enalapril 20 mg (ACE inhibitor).

Also known as: Jardiance 25 MG

Empagliflozin 25 mg arm (SGLT2 inhibitor)

Enalapril Maleate 20 mg DRUG

It is an ACE inhibitor, the active comparator in this trial, and is considered the gold standard for the treatment of diabetic kidney disease.

Also known as: Renitec 20 MG

Enalapril 20 mg arm (ACE inhibitor)

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men\& women with Type 2 Diabetic patient
• Age 30-65 years old
• UACR above 30mg/g
• eGFR between 30-90 ml/min/1.73m2
• Signed and dated informed consent
• Women must agree to use an effective birth control method if they are heterosexually active during the trial and should have a negative pregnancy test on day 1

You may not qualify if:

• T1DM, History of diabetic ketoacidosis, beta-cell or pancreas transplantation, or diabetes secondary to pancreatitis or pancreatectomy
• Age below 30 and above 65 years old
• hyperkalemia (i.e., K above 6)
• ESRF\& e GFR less than 30 ml/min/1.73m2
• renal artery stenosis
• type2 DM pregnant woman \& gestational DM, breastfeeding
• history of prior amputation or high risk for amputation (including severe peripheral vascular disease, neuropathy, and diabetic foot ulcers)
• History of one or more severe hypoglycemic episodes within 6 months prior to screening Idiopathic or hereditary angioedema
• allergies, or intolerance to trial medications or their excipients

Sponsors & Collaborators

• Omar Tarek Elfarargi: lead

Related Publications (1)

• Brenner, B. M., Cooper, M. E., De Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H. H., ... & Shahinfar, S. 2001.

  BACKGROUND

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

empagliflozin; Enalapril

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Omar T Elfarargi

  Primary health care corporation of Qatar

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Omar T Elfarargi

CONTACT

77438042; otabdelmoneim@phcc.gov.qa

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The trial will be double-blinded including both participants and health care providers to minimize the risk of bias. The blinding of outcome adjudicators and data collectors is unlikely to matter since the study outcomes are objective.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: principle investigator

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 13, 2022
• Study Start: March 1, 2023
• Primary Completion: March 1, 2024
• Study Completion: May 1, 2024
• Last Updated: May 13, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: approximately after 6 months of publication and for 4 years.