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Comparison Between the Efficacy of SGLT2 Inhibitor Therapy Versus ACE Inhibitor in the Treatment of Diabetic Kidney Disease (SGLT2i VS ACEi)

Primary Purpose

Diabetic Nephropathy Type 2

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Empagliflozin 25 MG
Enalapril Maleate 20 mg
Sponsored by
Omar Tarek Elfarargi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diabetic Nephropathy Type 2 focused on measuring diabetic kidney disease (DKD), SGLT2 inhibitors, ACE inhibitors

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Empagliflozin 25 mg arm (SGLT2 inhibitor)

    Enalapril 20 mg arm (ACE inhibitor)

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

    the change in Urine Albumin Creatinine Ratio (UACR)
    UACR (determined at first-morning void by at least 2 of 3 specimens obtained over a 3-to-6-month period) in mg/mmol

    Full Information

    First Posted
    May 5, 2022
    Last Updated
    May 9, 2022
    Sponsor
    Omar Tarek Elfarargi
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05373004
    Brief Title
    Comparison Between the Efficacy of SGLT2 Inhibitor Therapy Versus ACE Inhibitor in the Treatment of Diabetic Kidney Disease
    Acronym
    SGLT2i VS ACEi
    Official Title
    Comparison Between the Efficacy of Sodium-Glucose Co-transporter 2 Inhibitor Therapy Versus Angiotensin-converting Enzyme Inhibitor in the Treatment of Diabetic Kidney Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 2023 (Anticipated)
    Primary Completion Date
    March 2024 (Anticipated)
    Study Completion Date
    May 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Omar Tarek Elfarargi

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    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
    Detailed Description
    The gap that could noticeably be found in the available literature is that the studies done on SGLT2i were almost tested on people who already using ACEi or ARBs, thus it is unclear whether SGLT2i is used as a first-line instead of ACEi/ARB (If ACEi/ARB are contraindicated or intolerable), to what extent it will be effective in managing DKD compared to the proven effect of ACEi/ARBs alone? Although there is one subgroup analysis in the CANVAS trial to compare the effect of SGLT2 on patients who are on RAS blockers versus those without RAS blockers, the total number of participants who are not on RAS is very small (around 20%) compared to the total number of participants. the study consists of 2 equal arms, non-inferiority RCT that compares the change in the eGFR rate after one year between the ACEi (enalapril) group versus SGLT2i (empagliflozin) group in 212 men and non-pregnant women with DKD whom age 30-65 years old with UACR above 30mg/g and eGFR ranging from 30-90 ml/min/1.73m2. The study hypothesis is that the mean change of the eGFR in the ACEi group - Mean change of the eGFR in the SGLT2i group is < 5 ml/min/1.73m2 after one year. Results from this study will add to the current literature examining whether the use of SGLT2i, as a first-line or if ACEi is contraindicated or intolerable, is non-inferior to ACEi in preserving kidney function in DKD patients. Superiority could also be declared if present. Further studies with a longer period of time will be required for comparing the long-term effect of both medications on kidneys. Rational: Based on the ADA/EASD 2019 consensus, SGLT2 inhibitors are recommended in patients with type 2 diabetes in patients with CKD to prevent the progression of CKD (Buse et al.,2019). The interpretation of the CANVAS subgroup data is that performance of SGLT2i in patients NOT already on RAS inhibitor is good enough that the two 2 equal arms, non-inferiority would be ethically allowable. Since the existing data are insufficient to be analyzed to extract the answer to this question, "Which is better, an ACEI/ARB or an SGLT2i, to delay the progression of renal impairment?" we already know that the combination is effective but some patients may have a choice to make of one OR the other, this study provides a unique opportunity to tackle this gap in the literature. The reasons beyond the choice of Empagliflozin in this trial were based on many factors. the results of (the EMPA-REG OUTCOME) trial proved its efficacy in delaying the deterioration of kidney function and its availability in the local market. Moreover, it has a good safety profile in comparison to Canagliflozin (ex: risk of bone fracture, lower limb amputation).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Diabetic Nephropathy Type 2
    Keywords
    diabetic kidney disease (DKD), SGLT2 inhibitors, ACE inhibitors

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare Provider
    Masking Description
    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.
    Allocation
    Randomized
    Enrollment
    212 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Empagliflozin 25 mg arm (SGLT2 inhibitor)
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Enalapril 20 mg arm (ACE inhibitor)
    Arm Type
    Active Comparator
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Empagliflozin 25 MG
    Other Intervention Name(s)
    Jardiance 25 MG
    Intervention Description
    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).
    Intervention Type
    Drug
    Intervention Name(s)
    Enalapril Maleate 20 mg
    Other Intervention Name(s)
    Renitec 20 MG
    Intervention Description
    It is an ACE inhibitor, the active comparator in this trial, and is considered the gold standard for the treatment of diabetic kidney disease.
    Primary Outcome Measure Information:
    Title
    estimated glomerular filtration rate
    Description
    eGFR rate (determined by the Modification of Diet in Renal Disease [MDRD] equation) in ml/min/1.73m2
    Time Frame
    one year
    Secondary Outcome Measure Information:
    Title
    the change in Urine Albumin Creatinine Ratio (UACR)
    Description
    UACR (determined at first-morning void by at least 2 of 3 specimens obtained over a 3-to-6-month period) in mg/mmol
    Time Frame
    One year
    Other Pre-specified Outcome Measures:
    Title
    blood pressure
    Description
    measured in mmHg
    Time Frame
    One year
    Title
    the serum creatinine level
    Description
    measured in mg/dL
    Time Frame
    one year
    Title
    the rates of clinical events (myocardial infarction, ESRD, congestive heart failure, and stroke)
    Description
    if happened during the study
    Time Frame
    one year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    30 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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 Exclusion Criteria: 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Omar T Elfarargi
    Phone
    77438042
    Ext
    +974
    Email
    otabdelmoneim@phcc.gov.qa
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Omar T Elfarargi
    Organizational Affiliation
    Primary health care corporation of Qatar
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    All collected IPD will be shared after the end of the publication.
    IPD Sharing Time Frame
    approximately after 6 months of publication and for 4 years.
    Citations:
    Citation
    Brenner, B. M., Cooper, M. E., De Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H. H., ... & Shahinfar, S. 2001.
    Results Reference
    background

    Learn more about this trial

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

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