Diabetic Nephropathy Type 2Phase 2/3SGLT2i VS ACEiNCT05373004
Comparison Between the Efficacy of SGLT2 Inhibitor Therapy Versus ACE Inhibitor in the Treatment of Diabetic Kidney Disease
A Phase 2/3 study testing Empagliflozin 25 MG and Enalapril Maleate 20 mg in people with Diabetic Nephropathy Type 2, run by Omar Tarek Elfarargi.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 65 years
- Conditions the study is for
- Diabetic Nephropathy Type 2
- What is being tested?
- Empagliflozin 25 MG and Enalapril Maleate 20 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 212 participants
- Where
- No sites listed yet
- Study dates
- Mar 2023to May 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read more
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
Read the 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).
- Conditions
- Diabetic Nephropathy Type 2
- Being tested
- Empagliflozin 25 MG, Enalapril Maleate 20 mg
- Keywords
- diabetic kidney disease (DKD), SGLT2 inhibitors, ACE inhibitors
- Medical subject headings
- Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25 MGDrug
Also called Jardiance 25 MG
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).
Enalapril Maleate 20 mgDrug
Also called Renitec 20 MG
It is an ACE inhibitor, the active comparator in this trial, and is considered the gold standard for the treatment of diabetic kidney disease.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Enalapril Maleate 20 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
estimated glomerular filtration rate
eGFR rate (determined by the Modification of Diet in Renal Disease [MDRD] equation) in ml/min/1.73m2
Measured: one year
Secondary outcomes (1)
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
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2022
- Study startMar 2023 (estimated)
- Primary completionMar 2024 (estimated)
- Study completionMay 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic Nephropathy Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 212 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Omar Tarek Elfarargi
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Omar Tarek Elfarargi, Hamad General Hospital
- Investigators
- Omar T Elfarargi, Principal investigator, Primary health care corporation of Qatar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05373004
- Sponsor's protocol ID
- 54520
- Acronym
- SGLT2i VS ACEi
- Status last verified
- May 2022
- First submitted
- 5 May 2022
- Last updated
- 13 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected IPD will be shared after the end of the publication.
Publications
Brenner, B. M., Cooper, M. E., De Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H. H., ... & Shahinfar, S. 2001.
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05373004
- Acronym / sponsor ID
- SGLT2i VS ACEi / 54520
- Conditions
- Diabetic Nephropathy Type 2
- Keywords
- diabetic kidney disease (DKD), SGLT2 inhibitors, ACE inhibitors
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 212 participants (estimated)
- Lead sponsor
- Omar Tarek ElfarargiOther government
- Study start
- Mar 2023 (estimated)
- Primary completion
- Mar 2024 (estimated)
- Study completion
- May 2024 (estimated)
- First posted
- 13 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin 25 mg arm (SGLT2 inhibitor) | Experimental | Drug: Empagliflozin 25 MGempagliflozin 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 20 mg arm (ACE inhibitor) | Active comparator | Drug: Enalapril Maleate 20 mgenalapril 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. |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 25 MGAlso: Jardiance 25 MGIt 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). | Drug | Empagliflozin 25 mg arm (SGLT2 inhibitor) |
| Enalapril Maleate 20 mgAlso: Renitec 20 MGIt is an ACE inhibitor, the active comparator in this trial, and is considered the gold standard for the treatment of diabetic kidney disease. | Drug | Enalapril 20 mg arm (ACE inhibitor) |
Primary outcome
estimated glomerular filtration rate
Time frame: one year
eGFR rate (determined by the Modification of Diet in Renal Disease [MDRD] equation) in ml/min/1.73m2
1 secondary outcome
the change in Urine Albumin Creatinine Ratio (UACR)
Time frame: One year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2022.
- BackgroundBrenner, B. M., Cooper, M. E., De Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H. H., ... & Shahinfar, S. 2001.
- Individual participant dataSharing planned: Yes. All collected IPD will be shared after the end of the publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Omar T Elfarargi principal investigator
Primary health care corporation of Qatar
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Empagliflozin 25 MG and Enalapril Maleate 20 mg in people with Diabetic Nephropathy Type 2, run by Omar Tarek Elfarargi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 May 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Omar T Elfarargi (77438042 ext. +974, otabdelmoneim@phcc.gov.qa), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
estimated glomerular filtration rate (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05373004, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2022.