Coronary Disease With Diabetes MellitusPhase 4NCT03398577
Effects of SGLT2 Inhibitor in Diabetic Patients With Coronary Artery Disease
A Phase 4 study testing Dapagliflozin 10 MG [Farxiga] in people with Coronary Disease With Diabetes Mellitus, run by Sheba Medical Center at 1 site in Israel.
Trial summary
The aim of this study is to explore the effect of newly added SGLT2I medication or placebo, to standard medication regimen in diabetic patients with documented stable coronary disease. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Coronary Disease With Diabetes Mellitus
- What is being tested?
- Dapagliflozin 10 MG [Farxiga]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Feb 2018to 31 Dec 2018
- Phase
- Phase 4
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 Diabetes Mellitus on oral therapy
- Stable documented ischemic Heart disease (> 60 days post AMI, CABG or PCI)
- Sub-optimal Hb A1c defined as ≥ 7%
- Age > 21
- Life expectancy >1 year
Who cannot join
- Events of clinical hypoglycemia during the past 6 months
- Recent (< 60 days) acute coronary syndrome (ACS) or Cerebrovascular accident
- Transient ischemic attack (TIA) within the past year.
- Significant renal impairment (eGFR < 60 ml/min/1.73 m2)
- History of recurrent UTI \ vaginitis
- Past bladder cancer (TCC or other)
Show all 21Show fewer
- History of diabetic keto-acidosis
- Planned coronary intervention or planed surgical intervention (PCI or CABG)
- Unstable arrhythmias (i.e. rapid atrial fibrillation, symptomatic bradycardia, recurrent ventricular arrhythmia that are clinically significant, etc.)
- Known hypersensitivity to study drug
- Type I diabetes
- Current Hb A1c >9%
- Current Insulin treatment
- Active treatment with SGLT2I medication
- Inability to comply with study protocol
- Active malignancy other than basal cell carcinoma (BCC)
- Clinically advanced congestive heart failure - NYHA class III-IV
- Severe left ventricular dysfunction (LVEF<30%) with NYHA II or any NYHA class with documented recent heart failure decompensation (<3 months)
- Severe stable cardiac angina CCS III - IV or Unstable angina
- Chronic inflammation (i.e. IBD, Lupus, inflammatory arthritis, rheumatoid arthritis) or chronic infection (i.e. chronic diabetic foot infection)
- Pregnancy, lactation or child-bearing potential
Trial locations and contacts
1 site in 1 country.
Israel1 site
Sheba Medical Center, Cardiac Rehabilitation Institute
Tel HaShomer, 52621
About this study
Official title: Effects of SGLT2 Inhibitor on Markers of Inflammation, Atherosclerosis and Left Ventricular Strain in Diabetic Patients With Coronary Artery Disease
The aim of this study is to explore the effect of newly added SGLT2I medication or placebo, to standard medication regimen in diabetic patients with documented stable coronary disease. Therefore, in the present study the investigators plan to focus on possible anti-inflammatory and athero-thrombotic protective effects of Dapagliflozin compared to placebo, in secondary prevention population of stable coronary patients with diabetes. Additionally, the investigators will explore NT proBNP dynamics, which related to ventricular filling pressures in this specific population.
Read the detailed description
Patients with ischemic heart disease and diabetes are at a particularly high risk for the recurrence of cardiovascular events, conversely, certain classes of oral anti-diabetic medications have been shown to cause hypoglycemia with adverse cardiovascular implications 1,2. Diabetes induces complex vascular changes, promoting accelerated atherosclerosis and a hyper-coagulable state, as can be assessed indirectly by a number of markers. Principal perturbations include endothelial dysfunction, increased inflammatory plaque infiltration, adhesion molecule over-expression and adverse effects of circulating fatty acids and advanced glycosylation end-products.
Cardiovascular safety of anti-diabetic medications is of paramount importance and has been under recent FDA and EDQM scrutiny. A number of hypoglycemic drugs, especially sulfonylureas, have been associated with significant hypoglycemia and adverse events induced by sympathetic activation. Activation of the sympathetic system has numerous implications, including surges of heart rate, blood pressure but also pro-inflammatory and pro-coagulant effects. This partially explains increased cardiovascular adverse events noted with these drugs. Newer classes of antidiabetic medication have recently shown improved survival outcomes in patients with cardiovascular disease, yet the exact mechanisms of the observed risk reduction are mostly yet to be elucidated 3,4. One possible mechanism is anti-inflammatory effect exerted directly or indirectly by SGLT2I or diuretic effect leading to left ventricular unloading with NT pro BNP level reduction.
The aim of this study is to explore the effect of newly added SGLT2I medication or placebo, to standard medication regimen in diabetic patients with documented stable coronary disease. Reduction of inflammatory marker levels is of great clinical importance and has been shown to correlate with reduction in significant clinical events5. Therefore, in the present study we plan to focus on possible anti-inflammatory and athero-thrombotic protective effects of Dapagliflozin compared to placebo, in secondary prevention population of stable coronary patients with diabetes. Additionally, the investigators will explore NT proBNP dynamics, which related to ventricular filling pressures in this specific population.
Key representative markers for the present study are chosen in order to correctly represent alterations in: inflammation (hs-CRP, IL(interleukin) -1 beta, IL-6, P-Selectin, TNF-alfa), and LV strain (NT pro BNP).
The effect of SGLT2I on the above-mentioned parameters has not been studied in humans. Accordingly, the demonstration of significant improvements in markers of athero-thrombosis and inflammation in high-risk diabetic patients is of great clinical importance and novelty that may be employed for the reduction of major cardiovascular events in this population.
Importantly, the effects of SGLT2I therapy will be evaluated in a prospective controlled clinical trial in a closely supervised cardiac rehabilitation setting, which includes lifestyle changes, regular, quantifiable physical activity, and predefined nutritional interventions.
- Conditions
- Coronary Disease With Diabetes Mellitus
- Being tested
- Dapagliflozin 10 MG [Farxiga], Placebo Oral Tablet
- Keywords
- Coronary disease, diabetes, SGLT2I, Inflammation Mediators
- Medical subject headings
- Coronary Disease, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10 MG [Farxiga]Drug
Also called Farxiga
Computer based randomization software will be used in order to randomize eligible consenting subjects to placebo or Dapagliflozin 10 mg treatment using a 1:2 ratio.
Placebo Oral TabletDrug
Computer based randomization software will be used in order to randomize eligible consenting subjects to placebo or Dapagliflozin 10 mg treatment using a 1:2 ratio.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Eligible patients (HbA1C ≥ 7% and ≤ 9%) , who were allocated to the Intervention group will receive Dapagliflozin 10 mg in addition to oral anti-diabetic medication administered prior to study enrollment. Receives: Drug: Dapagliflozin 10 MG [Farxiga] |
| Control group | Placebo comparator | Eligible patients (HbA1C ≥ 7% and ≤ 9%) , who were allocated to the Control group will receive placebo in addition to oral anti-diabetic medication administered prior to study enrollment. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent reduction in interleukin (IL)-1β levels
Percent reduction in IL-1 β will be calculated as follows:(Baseline IL-1 minus follow-up [3-month] IL-1)/Baseline IL1; with value multiplied by 100.
Measured: 3 months
Secondary outcomes (7)
Percent reduction in additional biomarkers
Additional biomarkers including: IL-1 alpha, IL-8, IL-10, IL-17, tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP-1) . Percent reduction will be calculated as mentioned above
Measured: 3 months
Safety from events of clinical hypoglycemia
Events of clinical hypoglycemia are defined as:
palpitations, tremor, hunger, sweating and objective measurement of blood glucose ≤ 70 mg/dl
Measured: 3 Months
Reduction in BMI
Changes in BMI will be calculated according to weight and height measurements at enrollment comparing to its value following 3-month active treatment period.
Measured: 3 Months
Reduction in HB A1c
Reduction will be calculated by comparing HB A1c value at enrollment to its value following 3-month active treatment period.
Measured: 3 Months
NTpro BNP
Changes in BNP will be calculated by comparing it's value at enrollment to its value following 3-month active treatment period.
Measured: 3 Months
MMP-9 percent reduction
Percent reduction will be calculated as mentioned on outcome 1
Measured: 3 Months
Percent change in Adiponectin levels
Percent reduction will be calculated as mentioned on outcome 1
Measured: 3 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2018
- Study start1 Feb 2018 (estimated)
- Primary completion31 Aug 2018 (estimated)
- Study completion31 Dec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Disease With Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study is designed as a single-center, double-blinded, placebo controlled, 2-arm clinical trial to provide evidence on the effects of Dapagliflozin on key biomarkers of athero-thrombosis, inflammation and ventricular loading conditions (NT ProBNP).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 61 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr. Robert Klempfner Heart Rehabilitation Institute, Sheba Medical Center
- Investigators
- Robert Klempfner, Proffesor, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03398577
- Sponsor's protocol ID
- SGLT2
- Status last verified
- Jan 2018
- First submitted
- 21 Dec 2017
- Last updated
- 17 Jan 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of SGLT2 Inhibitor on Markers of Inflammation, Atherosclerosis and Left Ventricular Strain in Diabetic Patients With Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT03398577
- Acronym / sponsor ID
- SGLT2
- Conditions
- Coronary Disease With Diabetes Mellitus
- Keywords
- Coronary disease, diabetes, SGLT2I, Inflammation Mediators
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 61 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 1 Feb 2018 (estimated)
- Primary completion
- 31 Aug 2018 (estimated)
- Study completion
- 31 Dec 2018 (estimated)
- First posted
- 12 Jan 2018 (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.
The aim of this study is to explore the effect of newly added SGLT2I medication or placebo, to standard medication regimen in diabetic patients with documented stable coronary disease. Therefore, in the present study the investigators plan to focus on possible anti-inflammatory and athero-thrombotic protective effects of Dapagliflozin compared to placebo, in secondary prevention population of stable coronary patients with diabetes. Additionally, the investigators will explore NT proBNP dynamics, which related to ventricular filling pressures in this specific population.
Detailed description
Patients with ischemic heart disease and diabetes are at a particularly high risk for the recurrence of cardiovascular events, conversely, certain classes of oral anti-diabetic medications have been shown to cause hypoglycemia with adverse cardiovascular implications 1,2. Diabetes induces complex vascular changes, promoting accelerated atherosclerosis and a hyper-coagulable state, as can be assessed indirectly by a number of markers. Principal perturbations include endothelial dysfunction, increased inflammatory plaque infiltration, adhesion molecule over-expression and adverse effects of circulating fatty acids and advanced glycosylation end-products.
Cardiovascular safety of anti-diabetic medications is of paramount importance and has been under recent FDA and EDQM scrutiny. A number of hypoglycemic drugs, especially sulfonylureas, have been associated with significant hypoglycemia and adverse events induced by sympathetic activation. Activation of the sympathetic system has numerous implications, including surges of heart rate, blood pressure but also pro-inflammatory and pro-coagulant effects. This partially explains increased cardiovascular adverse events noted with these drugs. Newer classes of antidiabetic medication have recently shown improved survival outcomes in patients with cardiovascular disease, yet the exact mechanisms of the observed risk reduction are mostly yet to be elucidated 3,4. One possible mechanism is anti-inflammatory effect exerted directly or indirectly by SGLT2I or diuretic effect leading to left ventricular unloading with NT pro BNP level reduction.
The aim of this study is to explore the effect of newly added SGLT2I medication or placebo, to standard medication regimen in diabetic patients with documented stable coronary disease. Reduction of inflammatory marker levels is of great clinical importance and has been shown to correlate with reduction in significant clinical events5. Therefore, in the present study we plan to focus on possible anti-inflammatory and athero-thrombotic protective effects of Dapagliflozin compared to placebo, in secondary prevention population of stable coronary patients with diabetes. Additionally, the investigators will explore NT proBNP dynamics, which related to ventricular filling pressures in this specific population.
Key representative markers for the present study are chosen in order to correctly represent alterations in: inflammation (hs-CRP, IL(interleukin) -1 beta, IL-6, P-Selectin, TNF-alfa), and LV strain (NT pro BNP).
The effect of SGLT2I on the above-mentioned parameters has not been studied in humans. Accordingly, the demonstration of significant improvements in markers of athero-thrombosis and inflammation in high-risk diabetic patients is of great clinical importance and novelty that may be employed for the reduction of major cardiovascular events in this population.
Importantly, the effects of SGLT2I therapy will be evaluated in a prospective controlled clinical trial in a closely supervised cardiac rehabilitation setting, which includes lifestyle changes, regular, quantifiable physical activity, and predefined nutritional interventions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- The study is designed as a single-center, double-blinded, placebo controlled, 2-arm clinical trial to provide evidence on the effects of Dapagliflozin on key biomarkers of athero-thrombosis, inflammation and ventricular loading conditions (NT ProBNP).
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Drug: Dapagliflozin 10 MG [Farxiga]Eligible patients (HbA1C ≥ 7% and ≤ 9%) , who were allocated to the Intervention group will receive Dapagliflozin 10 mg in addition to oral anti-diabetic medication administered prior to study enrollment. |
| Control group | Placebo comparator | Drug: Placebo Oral TabletEligible patients (HbA1C ≥ 7% and ≤ 9%) , who were allocated to the Control group will receive placebo in addition to oral anti-diabetic medication administered prior to study enrollment. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Type 2 Diabetes Mellitus on oral therapy
- Stable documented ischemic Heart disease (> 60 days post AMI, CABG or PCI)
- Sub-optimal Hb A1c defined as ≥ 7%
- Age > 21
- Life expectancy >1 year
Key exclusion criteria (21 listed)
- Events of clinical hypoglycemia during the past 6 months
- Recent (< 60 days) acute coronary syndrome (ACS) or Cerebrovascular accident
- Transient ischemic attack (TIA) within the past year.
- Significant renal impairment (eGFR < 60 ml/min/1.73 m2)
- History of recurrent UTI \ vaginitis
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 |
|---|---|---|
| Dapagliflozin 10 MG [Farxiga]Also: FarxigaComputer based randomization software will be used in order to randomize eligible consenting subjects to placebo or Dapagliflozin 10 mg treatment using a 1:2 ratio. | Drug | Intervention group |
| Placebo Oral TabletComputer based randomization software will be used in order to randomize eligible consenting subjects to placebo or Dapagliflozin 10 mg treatment using a 1:2 ratio. | Drug | Control group |
Primary outcome
Percent reduction in interleukin (IL)-1β levels
Time frame: 3 months
Percent reduction in IL-1 β will be calculated as follows:(Baseline IL-1 minus follow-up [3-month] IL-1)/Baseline IL1; with value multiplied by 100.
7 secondary outcomes
Percent reduction in additional biomarkers
Time frame: 3 months
Safety from events of clinical hypoglycemia
Time frame: 3 Months
Reduction in BMI
Time frame: 3 Months
Reduction in HB A1c
Time frame: 3 Months
NTpro BNP
Time frame: 3 Months
MMP-9 percent reduction
Time frame: 3 Months
Percent change in Adiponectin levels
Time frame: 3 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
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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.
Robert Klempfner, Proffesor principal investigator
Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dapagliflozin 10 MG [Farxiga] in people with Coronary Disease With Diabetes Mellitus, run by Sheba Medical Center at 1 site in Israel.
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 5 inclusion and 21 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 17 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Gal Shmukler, MA (+972-3-5344703, Gal.Shmukler@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent reduction in interleukin (IL)-1β levels (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jan 2018; AzTrials last refreshed its copy on 8 Nov 2026.