Trial Outcomes & Findings for Efficacy and Safety of Dapagliflozin in Acute Heart Failure (NCT NCT04298229)

Last Updated: 2024-03-15

Results Overview

cumulative change in weight (kilograms) per 40mg of IV furosemide equivalents from enrollment to day 5 or discharge (if earlier) between protocolized diuretic therapy and dapagliflozin plus protocolized diuretic therapy guided by urine output

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

240 participants

Primary outcome timeframe

Baseline to Day 5 or discharge if earlier

Results posted on

2024-03-15

Participant Flow

A total of 240 patients were randomized to either Structured usual care or Dapagliflozin plus Structured usual care treatment arms

Participant milestones

Participant milestones
Measure	Structured Usual Care Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.	Dapagliflozin Plus Structured Usual Care Dapagliflozin 10 MG: SGLT2 inhibitors being investigated for its diuretic and natriuretic effects on top of protocolized diuretic therapy. Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.
Overall Study STARTED	120	120
Overall Study COMPLETED	116	118
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Structured Usual Care Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.	Dapagliflozin Plus Structured Usual Care Dapagliflozin 10 MG: SGLT2 inhibitors being investigated for its diuretic and natriuretic effects on top of protocolized diuretic therapy. Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	1	1
Overall Study Did not receive IV loop diuretics	2	0

Baseline Characteristics

Efficacy and Safety of Dapagliflozin in Acute Heart Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Structured Usual Care n=119 Participants Structured usual care arm with protocolized diuretic therapy based on urine output.	Dapagliflozin + Structured Usual Care n=119 Participants Dapagliflozin 10 MG once daily + Structured usual care arm with protocolized diuretic therapy based on urine output.	Total n=238 Participants Total of all reporting groups
Age, Continuous	64 years n=5 Participants	65 years n=7 Participants	65 years n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	41 Participants n=7 Participants	93 Participants n=5 Participants
Sex: Female, Male Male	67 Participants n=5 Participants	78 Participants n=7 Participants	145 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	29 Participants n=5 Participants	39 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) White	84 Participants n=5 Participants	79 Participants n=7 Participants	163 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	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Left ventricular ejection fraction	35 Percentage of ejection fraction n=5 Participants	45 Percentage of ejection fraction n=7 Participants	40 Percentage of ejection fraction n=5 Participants
systolic blood pressure	120 mmHg n=5 Participants	121 mmHg n=7 Participants	121 mmHg n=5 Participants
estimated Glomerular Filtration Rate (eGFR)	54 mL/min/1.73m2 n=5 Participants	51 mL/min/1.73m2 n=7 Participants	53 mL/min/1.73m2 n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 5 or discharge if earlier

Outcome measures

Outcome measures
Measure	Structured Usual Care n=116 Participants Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.	Dapagliflozin Plus Structured Usual Care n=118 Participants Dapagliflozin 10 MG: SGLT2 inhibitors being investigated for its diuretic and natriuretic effects on top of protocolized diuretic therapy. Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.
Cumulative Change in Weight (Kilograms) Per 40mg of IV Furosemide Equivalents, Adjusted for Baseline Weight	-0.31 kg/40mg IV furosemide Interval -0.39 to -0.23	-0.42 kg/40mg IV furosemide Interval -0.52 to -0.33

SECONDARY outcome

Timeframe: Baseline to hospital discharge, an average of 5 days

Number of participants with worsening heart failure during hospitalization requiring IV inotropic therapy with dobutamine, milrinone, or dopamine or admission to an intensive care unit as adjudicated by the Clinical Event Adjudication Committee

Outcome measures

Outcome measures
Measure	Structured Usual Care n=116 Participants Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.	Dapagliflozin Plus Structured Usual Care n=118 Participants Dapagliflozin 10 MG: SGLT2 inhibitors being investigated for its diuretic and natriuretic effects on top of protocolized diuretic therapy. Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.
Number of Participants With Inpatient Worsening Heart Failure	3 participants	4 participants

SECONDARY outcome

Timeframe: Day 30

Hospital readmission within 30 days of discharge for heart failure or diabetic reasons as adjudicated by the Clinical Event Adjudication Committee

Outcome measures

Outcome measures
Measure	Structured Usual Care n=116 Participants Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.	Dapagliflozin Plus Structured Usual Care n=118 Participants Dapagliflozin 10 MG: SGLT2 inhibitors being investigated for its diuretic and natriuretic effects on top of protocolized diuretic therapy. Protocolized Diuretic Therapy: Structured usual care arm with protocolized diuretic therapy based on urine output.
Hospital Readmission	20 Participants	19 Participants

Adverse Events

Structured Usual Care

Serious events: 7 serious events

Other events: 17 other events

Deaths: 5 deaths

Dapagliflozin + Structured Usual Care

Serious events: 6 serious events

Other events: 13 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Structured Usual Care n=119 participants at risk Structured usual care arm with protocolized diuretic therapy based on urine output.	Dapagliflozin + Structured Usual Care n=119 participants at risk Dapagliflozin 10 MG once daily + Structured usual care arm with protocolized diuretic therapy based on urine output.
Endocrine disorders Ketoacidosis	0.00% 0/119 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge	0.00% 0/119 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge
Cardiac disorders Severe Hypotension	0.84% 1/119 • Number of events 1 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge	0.84% 1/119 • Number of events 1 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge
Endocrine disorders Severe hypoglycemia	0.00% 0/119 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge	0.00% 0/119 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge
Renal and urinary disorders Acute Kidney Injury	0.84% 1/119 • Number of events 1 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge	1.7% 2/119 • Number of events 2 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge
Cardiac disorders Death	4.2% 5/119 • Number of events 5 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge	2.5% 3/119 • Number of events 3 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge

Other adverse events

Other adverse events
Measure	Structured Usual Care n=119 participants at risk Structured usual care arm with protocolized diuretic therapy based on urine output.	Dapagliflozin + Structured Usual Care n=119 participants at risk Dapagliflozin 10 MG once daily + Structured usual care arm with protocolized diuretic therapy based on urine output.
Endocrine disorders Hypoglycemia	7.6% 9/119 • Number of events 9 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge	5.9% 7/119 • Number of events 7 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge
Cardiac disorders HF exacerbation	6.7% 8/119 • Number of events 8 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge	5.0% 6/119 • Number of events 6 • Adverse events were assessment from enrollment through 30-days after hospital discharge, on average 36 days from baseline AE were collected during daily monitoring while the patient was hospitalized during the index hospitalization and via 30-day follow-up phone calls after discharge

Additional Information

Zachary Cox

Vanderbilt University Medical Center

Phone: 615-966-7107

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place