Trial Outcomes & Findings for Effects of SGLT-2 Inhibition on Myocardial Fibrosis and Inflammation as Assessed by Cardiac MRI in Patients With DM2 (NCT NCT03782259)
NCT ID: NCT03782259
Last Updated: 2023-12-29
Results Overview
Cardiac MRI using T1-mapping is capable of quantifying myocardial extracellular volume (ECV), a surrogate of fibrosis, with excellent inter- and intra-observer variability. Cardiac fibrosis was assessed by cardiac MRI T1 mapping to calculate ECV at two timepoints, baseline and at approximately 1 year. ECV combines native and contrast-enhanced T1 mapping. Extracellular Volume (ECV) maps were generated offline using MATLAB software. ECV was calculated from native and post-contrast T1 values for blood and myocardial tissue, the partition coefficient lambda (λ), and hematocrit using the following formulas: ECV = λ(1-hematocrit); λ = (1/T1 myocardium post-contrast-1/T1 myocardium-native)/(1/T1 blood post-contrast-1/T1 blood-native).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
62 participants
Primary outcome timeframe
Approximately 12 Months
Results posted on
2023-12-29
Participant Flow
Participant milestones
| Measure |
Placebo
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
31
|
|
Overall Study
COMPLETED
|
29
|
27
|
|
Overall Study
NOT COMPLETED
|
2
|
4
|
Reasons for withdrawal
| Measure |
Placebo
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Moved out of state
|
0
|
2
|
|
Overall Study
MRI incompatibility: Pacemaker implanted prior to subject final MRI scan
|
0
|
1
|
|
Overall Study
Subject discontinued intervention
|
1
|
0
|
Baseline Characteristics
Effects of SGLT-2 Inhibition on Myocardial Fibrosis and Inflammation as Assessed by Cardiac MRI in Patients With DM2
Baseline characteristics by cohort
| Measure |
Placebo
n=31 Participants
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
n=31 Participants
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
STANDARD_DEVIATION 11 • n=5 Participants
|
62 years
STANDARD_DEVIATION 9 • n=7 Participants
|
62 years
STANDARD_DEVIATION 10 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
27 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=5 Participants
|
31 participants
n=7 Participants
|
62 participants
n=5 Participants
|
|
Hypertension
|
19 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Diabetes mellitus
|
31 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
Hyperlipidemia
|
18 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Current smoker
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Family history myocardial infarction
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Family history stroke
|
11 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
History myocardial infarction
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Angina
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Coronary artery bypass surgery
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Percutaneous coronary intervention
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Approximately 12 MonthsCardiac MRI using T1-mapping is capable of quantifying myocardial extracellular volume (ECV), a surrogate of fibrosis, with excellent inter- and intra-observer variability. Cardiac fibrosis was assessed by cardiac MRI T1 mapping to calculate ECV at two timepoints, baseline and at approximately 1 year. ECV combines native and contrast-enhanced T1 mapping. Extracellular Volume (ECV) maps were generated offline using MATLAB software. ECV was calculated from native and post-contrast T1 values for blood and myocardial tissue, the partition coefficient lambda (λ), and hematocrit using the following formulas: ECV = λ(1-hematocrit); λ = (1/T1 myocardium post-contrast-1/T1 myocardium-native)/(1/T1 blood post-contrast-1/T1 blood-native).
Outcome measures
| Measure |
Placebo
n=29 Participants
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
n=27 Participants
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
Extracellular Volume Fraction (ECV)
Baseline
|
28.5 Percentage of total tissue volume
Standard Deviation 2.1
|
27.7 Percentage of total tissue volume
Standard Deviation 2.9
|
|
Extracellular Volume Fraction (ECV)
1 year
|
28.7 Percentage of total tissue volume
Standard Deviation 2.3
|
28.4 Percentage of total tissue volume
Standard Deviation 2.0
|
|
Extracellular Volume Fraction (ECV)
Difference (1 year - baseline)
|
0.24 Percentage of total tissue volume
Standard Deviation 2.16
|
0.71 Percentage of total tissue volume
Standard Deviation 2.75
|
PRIMARY outcome
Timeframe: Approximately 12 MonthsGlobal myocardial strain measured from cardiac MRI with T1-mapping at two timepoints. MRI at Randomization and MRI at approximately 12 Months. Myocardial strain measurements with feature tracking will be performed to measure myocardial strain from the Balanced Steady State Free Precession (bSSFP) short-axis and long-axis cine images. Long-axis cine images will be further used to compute global myocardial strain. Ancova test with adjusted for baseline global myocardial strain will be used to compare change in global myocardial strain over 12 months between 2 treatment groups. Global myocardial strain reported as longitudinal, radial, and circumferential at baseline and 1 year.
Outcome measures
| Measure |
Placebo
n=31 Participants
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
n=31 Participants
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
Global Myocardial Strain
Global myocardial longitudinal strain - Baseline
|
-11.0 Change in length as a percentage
Standard Deviation 3.9
|
-12.9 Change in length as a percentage
Standard Deviation 3.4
|
|
Global Myocardial Strain
Global myocardial longitudinal strain - 1 year
|
-11.3 Change in length as a percentage
Standard Deviation 5.1
|
-12.0 Change in length as a percentage
Standard Deviation 3.8
|
|
Global Myocardial Strain
Global myocardial longitudinal strain - Difference (1 year - baseline)
|
-0.24 Change in length as a percentage
Standard Deviation 5.32
|
0.88 Change in length as a percentage
Standard Deviation 4.06
|
|
Global Myocardial Strain
Global myocardial radial strain - Baseline
|
27.3 Change in length as a percentage
Standard Deviation 7.1
|
31.2 Change in length as a percentage
Standard Deviation 8.7
|
|
Global Myocardial Strain
Global myocardial radial strain - 1 year
|
31.3 Change in length as a percentage
Standard Deviation 10.4
|
33.9 Change in length as a percentage
Standard Deviation 9.5
|
|
Global Myocardial Strain
Global myocardial radial strain - Difference (1 year - baseline)
|
4.01 Change in length as a percentage
Standard Deviation 10.19
|
2.71 Change in length as a percentage
Standard Deviation 9.38
|
|
Global Myocardial Strain
Global myocardial circumferential strain - Baseline
|
-15.7 Change in length as a percentage
Standard Deviation 2.8
|
-17.8 Change in length as a percentage
Standard Deviation 2.9
|
|
Global Myocardial Strain
Global myocardial circumferential strain - 1 year
|
-16.7 Change in length as a percentage
Standard Deviation 2.9
|
-17.7 Change in length as a percentage
Standard Deviation 3.6
|
|
Global Myocardial Strain
Global myocardial circumferential strain - Difference (1 year - baseline)
|
-0.97 Change in length as a percentage
Standard Deviation 3.28
|
0.05 Change in length as a percentage
Standard Deviation 3.21
|
SECONDARY outcome
Timeframe: Approximately 12 MonthsChange from baseline in T2 relaxation time measured from cardiac MRI with T2-mapping at two timepoints. MRI at Randomization and MRI at approximately 12 Months
Outcome measures
| Measure |
Placebo
n=31 Participants
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
n=31 Participants
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
T2 Relaxation Time
Baseline
|
48.6 milliseconds
Standard Deviation 3.3
|
50.5 milliseconds
Standard Deviation 4.3
|
|
T2 Relaxation Time
1 year
|
50.2 milliseconds
Standard Deviation 3.8
|
50.0 milliseconds
Standard Deviation 5.7
|
|
T2 Relaxation Time
Difference (1 year - baseline)
|
1.61 milliseconds
Standard Deviation 4.14
|
-0.51 milliseconds
Standard Deviation 6.59
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Approximately 12 MonthsFasting glucose assessed at Baseline and every 3 months for approximately 12 months, Baseline and 12 months reported
Outcome measures
| Measure |
Placebo
n=31 Participants
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
n=31 Participants
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
Fasting Glucose
Baseline
|
164.5 mg/dL
Standard Deviation 46.4
|
159.8 mg/dL
Standard Deviation 42.5
|
|
Fasting Glucose
1 year
|
161.0 mg/dL
Standard Deviation 55.9
|
126.8 mg/dL
Standard Deviation 36.9
|
|
Fasting Glucose
Difference (1 year - baseline)
|
-3.48 mg/dL
Standard Deviation 39.56
|
-33.04 mg/dL
Standard Deviation 55.08
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Approximately 12 MonthsHemoglobin A1c (HbA1c) assessed at Baseline and every 3 months for approximately 12 months, Baseline and 12 months reported
Outcome measures
| Measure |
Placebo
n=31 Participants
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
n=31 Participants
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
HbA1C
Baseline
|
7.8 percentage
Standard Deviation 0.9
|
7.9 percentage
Standard Deviation .8
|
|
HbA1C
1 year
|
8.0 percentage
Standard Deviation 1.0
|
7.4 percentage
Standard Deviation .8
|
|
HbA1C
Difference (1 year - baseline)
|
0.11 percentage
Standard Deviation 1.17
|
-.52 percentage
Standard Deviation 0.95
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Approximately 12 MonthsInflammatory marker hsCRP assessed at Baseline and every 6 months for approximately 12 months, Baseline and 12 months reported
Outcome measures
| Measure |
Placebo
n=31 Participants
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Dapagliflozin
n=31 Participants
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
hsCRP
Baseline
|
2.4 mg/dL
Standard Deviation .5
|
1.7 mg/dL
Standard Deviation 1.6
|
|
hsCRP
1 year
|
1.8 mg/dL
Standard Deviation .3
|
2.5 mg/dL
Standard Deviation 4.1
|
|
hsCRP
Difference (1 year - baseline)
|
.12 mg/dL
Standard Deviation 2.20
|
0.81 mg/dL
Standard Deviation 2.95
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Active
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=31 participants at risk
10mg tabs placebo matching dapagliflozin.
Placebo: Placebo
|
Active
n=31 participants at risk
10mg tabs of dapagliflozin
dapagliflozin: Subjects will either receive 10mg tabs of dapagliflozin or identical looking placebo - inactive medication. Subjects have an equal chance of receiving dapagliflozin or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects nor the Study Site personnel will know which treatment subjects are assigned to. The study drug must be taken daily. The subject's other medications will not be changed by the study.
|
|---|---|---|
|
Cardiac disorders
Non-ST-elevation myocardial infarction
|
3.2%
1/31 • Number of events 1 • Study screening visit to subject completion, approximately 13 months per subject.
Adverse events were assessed at each of the subject visits.
|
0.00%
0/31 • Study screening visit to subject completion, approximately 13 months per subject.
Adverse events were assessed at each of the subject visits.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place