Trial Outcomes & Findings for ERtugliflozin triAl in DIabetes With Preserved or Reduced ejeCtion FrAcTion mEchanistic Evaluation in Heart Failure (NCT NCT03416270)
NCT ID: NCT03416270
Last Updated: 2025-05-06
Results Overview
The difference in fractional excretion of lithium (FELi) with ertugliflozin vs. placebo. This was measured using exogenous lithium administration 12 hours before lithium excretion was measured in urine and blood.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
34 participants
Primary outcome timeframe
Change in outcomes was measured acute (1 week minus baseline values) and chronic (12 weeks minus baseline values)
Results posted on
2025-05-06
Participant Flow
Participant milestones
| Measure |
Ertuglifozin Treatment Arm
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
17
|
|
Overall Study
COMPLETED
|
17
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
ERtugliflozin triAl in DIabetes With Preserved or Reduced ejeCtion FrAcTion mEchanistic Evaluation in Heart Failure
Baseline characteristics by cohort
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks.
|
Placebo Arm
n=17 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks.
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.8 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
69.4 years
STANDARD_DEVIATION 7.5 • n=7 Participants
|
69.6 years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
8 participants
n=5 Participants
|
8 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
9 participants
n=5 Participants
|
9 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
eGFR
|
63.5 mL/min/1.73 m2
STANDARD_DEVIATION 23.3 • n=5 Participants
|
66.4 mL/min/1.73 m2
STANDARD_DEVIATION 22.4 • n=7 Participants
|
65 mL/min/1.73 m2
STANDARD_DEVIATION 22.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Change in outcomes was measured acute (1 week minus baseline values) and chronic (12 weeks minus baseline values)The difference in fractional excretion of lithium (FELi) with ertugliflozin vs. placebo. This was measured using exogenous lithium administration 12 hours before lithium excretion was measured in urine and blood.
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Fractional Excretion of Lithium (FELi)
Week 1
|
0.3 percentage of filtered lithium excreted
Standard Error 6.9
|
-2.3 percentage of filtered lithium excreted
Standard Error 16.8
|
|
Fractional Excretion of Lithium (FELi)
Week 12
|
0.8 percentage of filtered lithium excreted
Standard Error 11.0
|
-4.9 percentage of filtered lithium excreted
Standard Error 16.6
|
PRIMARY outcome
Timeframe: Change in outcomes was measured acute (1 week minus baseline values) and chronic (12 weeks minus baseline values)The difference in fractional excretion of sodium (FENa) with ertugliflozin vs. placebo. This was measured using exogenous lithium administration 12 hours before sodium excretion was measured in urine and blood.
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Fractional Excretion of Sodium (FENa)
Week 1
|
-0.6 percentage of sodium excretion
Standard Error 1.9
|
0.3 percentage of sodium excretion
Standard Error 1.7
|
|
Fractional Excretion of Sodium (FENa)
Week 12
|
-0.6 percentage of sodium excretion
Standard Error 1.6
|
0.1 percentage of sodium excretion
Standard Error 1.3
|
PRIMARY outcome
Timeframe: Change in outcomes was measured acute (1 week minus baseline values) and chronic (12 weeks minus baseline values)The difference in fractional excretion of lithium and fractional excretion of sodium (calculated by the difference between FELi and FENa) with ertugliflozin vs. placebo. This was measured using exogenous lithium administration 12 hours before sodium excretion was measured in urine and blood.
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Change in Absolute Fractional Distal Sodium Reabsorption From Baseline (FELi-FENa)
Week 1
|
0.8 percentage of total sodium reabsorption
Standard Error 7.0
|
-2.6 percentage of total sodium reabsorption
Standard Error 16.7
|
|
Change in Absolute Fractional Distal Sodium Reabsorption From Baseline (FELi-FENa)
Week 12
|
1.4 percentage of total sodium reabsorption
Standard Error 10.6
|
-5 percentage of total sodium reabsorption
Standard Error 16.1
|
SECONDARY outcome
Timeframe: Glomerular Filtration Rate (GFR, based on plasma iohexol clearance) will be measured at 12 weeksThe difference in iohexol-measured GFR with ertugliflozin vs. placebo. 5ml bolus iohexol (Omnipaque 300mg) was infused intravenously over 2 minutes while participants were supine. Iohexol disappearance curve was used to measure GFR over from 2-4 hours after infusion.
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Glomerular Filtration Rate (GFR)
|
48.6 mL/min/1.73 m2
Standard Error 4.0
|
50.1 mL/min/1.73 m2
Standard Error 4.2
|
SECONDARY outcome
Timeframe: Effective Renal Plasma Flow (ERPF, based on paraaminohippurate plasma clearance) will be measured at 12 weeksThe difference in ERPF with ertugliflozin vs. placebo. Paraaminohippurate (PAH) was intravenously administered to measured ERPF.
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Effective Renal Plasma Flow (ERPF)
|
399.1 mL/min/1.73 m2
Standard Error 46.8
|
335.6 mL/min/1.73 m2
Standard Error 41.5
|
SECONDARY outcome
Timeframe: chronic (12 weeks)The difference in seated SBP with ertugliflozin vs. placebo
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Systolic Blood Pressure (SBP)
|
132 mmHg
Standard Error 5
|
128 mmHg
Standard Error 5
|
SECONDARY outcome
Timeframe: chronic (12 weeks)The difference in seated DBP with ertugliflozin vs. placebo
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Diastolic Blood Pressure (DBP)
|
77 mmHg
Standard Error 3
|
76 mmHg
Standard Error 3
|
SECONDARY outcome
Timeframe: chronic (12 weeks)The difference in seated HR with ertugliflozin vs. placebo
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Heart Rate (HR)
|
74 bpm
Standard Error 3
|
72 bpm
Standard Error 3
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Echocardiography for markers of systolic and diastolic function
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
LV Ejection Fraction
|
49.2 percentage of output
Standard Error 4.4
|
43.6 percentage of output
Standard Error 5.4
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Arterial Stiffness using SphygmaCor software. Pulse points measured at carotid and femoral arteries.
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Carotid-femoral Pulse Wave Velocity
|
11.50 m/s
Standard Error 1.50
|
12.14 m/s
Standard Error 1.42
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Population: The plasma volume was calculated from the laboratory-measured indocyanine green dye values in n=18 participants who had measurements performed.
Plasma volume will be measured using a non-radioactive technique (indocyanine green dilution)
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=9 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=9 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Plasma Volume
|
3470.9 ml
Standard Error 438
|
3158.2 ml
Standard Error 491.9
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Extracellular water will be measured non-invasively using bioimpedence spectroscopy
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Extracellular Water
|
20.1 L
Standard Error 0.9
|
21.8 L
Standard Error 1.0
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Cardiac output will also be measured using non-invasive cardiac monitoring (NICOM)
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Cardiac Output
|
5.8 L/min
Standard Error 0.3
|
5.8 L/min
Standard Error 0.3
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Systemic vascular resistance will also be measured using non-invasive cardiac monitoring (NICOM)
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Systemic Vascular Resistance
|
1346.7 dynes·s·cm5
Standard Error 99.1
|
1437.1 dynes·s·cm5
Standard Error 99.9
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Neurohormones/biomarkers
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Blood Angiotensin II
|
89.2 pg/ml
Standard Error 7.1
|
86.5 pg/ml
Standard Error 7.3
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Neurohormones/biomarkers
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
BNP
|
1311.1 pg/ml
Standard Error 400.5
|
576.6 pg/ml
Standard Error 405.3
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Neurohormones/biomarkers
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Norepinephrine
|
2.6 nM
Standard Error 0.3
|
2.6 nM
Standard Error 0.3
|
SECONDARY outcome
Timeframe: chronic (12 weeks)Neurohormones/biomarkers
Outcome measures
| Measure |
Ertuglifozin Treatment Arm
n=17 Participants
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
|
Placebo Arm
n=16 Participants
Placebo Matching Ertugliflozin Tablet for 12 weeks
|
|---|---|---|
|
Urinary Adenosine
|
0.25 mM/μmol Cr
Standard Error 0.05
|
0.39 mM/μmol Cr
Standard Error 0.05
|
Adverse Events
Ertuglifozin Treatment Arm
Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo Arm
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ertuglifozin Treatment Arm
n=17 participants at risk
Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) for 12 weeks
Ertugliflozin: Ertugliflozin Tablets Total Dose 15mg (10mg + 5 mg) once daily for 12 weeks
|
Placebo Arm
n=17 participants at risk
Placebo Matching Ertugliflozin Tablet for 12 weeks
Placebo: Placebo once daily for 12 weeks
|
|---|---|---|
|
Cardiac disorders
Heart failure hospitalization
|
5.9%
1/17 • Number of events 3 • 12 weeks
|
0.00%
0/17 • 12 weeks
|
|
Gastrointestinal disorders
Emesis
|
5.9%
1/17 • Number of events 1 • 12 weeks
|
5.9%
1/17 • Number of events 1 • 12 weeks
|
|
Cardiac disorders
Myocardial infarction
|
5.9%
1/17 • Number of events 1 • 12 weeks
|
0.00%
0/17 • 12 weeks
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place