Trial Outcomes & Findings for A Study That Looks at the Function of the Heart in Patients With Heart Failure Who Take Empagliflozin (NCT NCT03332212)

Last Updated: 2021-06-18

Results Overview

The primary endpoint of efficacy was the change from baseline to Week 12 in phosphocreatine/adenosine triphosphate (PCr/ATP) ratio in the resting state measured by 31P cardiac magnetic resonance spectroscopy (MRS). Adjusted mean values were calculated using an analysis of variance (ANOVA) model, with treatment, history of diabetes, and history of atrial fibrillation (AF) as fixed effects.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

72 participants

Primary outcome timeframe

At baseline and at week 12.

Results posted on

2021-06-18

Participant Flow

A randomised, double-blind, placebo controlled, mechanistic cardiac magnetic resonance study to investigate the effects of empagliflozin treatment on cardiac physiology and metabolism in patients with heart failure.

All subjects were screened for eligibility to participate in trial. Subjects attended specialist site to ensure that they (the subjects) met all implemented inclusion/exclusion criteria.

Participant milestones

Participant milestones
Measure	Placebo Cohort A Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF).	Placebo Cohort B Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).	Empagliflozin 10mg Cohort A Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF).	Empagliflozin 10mg Cohort B Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).
Overall Study STARTED	19	18	17	18
Overall Study Treated	19	17	17	18
Overall Study COMPLETED	18	16	17	17
Overall Study NOT COMPLETED	1	2	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Cohort A Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF).	Placebo Cohort B Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).	Empagliflozin 10mg Cohort B Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).
Overall Study Not treated	0	1	0
Overall Study Adverse Event	0	0	1
Overall Study worsening of disease under study	1	1	0

Baseline Characteristics

In the Placebo arm (Cohort B) there was one patient without baseline Cardiac magnetic resonance (CMR) measures.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Cohort A n=19 Participants Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF).	Placebo Cohort B n=18 Participants Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).	Empagliflozin 10mg Cohort A n=17 Participants Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF).	Empagliflozin 10mg Cohort B n=18 Participants Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).	Total n=72 Participants Total of all reporting groups
Age, Continuous	64.7 Years STANDARD_DEVIATION 12.7 • n=19 Participants	72.1 Years STANDARD_DEVIATION 7.0 • n=18 Participants	67.5 Years STANDARD_DEVIATION 14.1 • n=17 Participants	69.1 Years STANDARD_DEVIATION 10.9 • n=18 Participants	68.3 Years STANDARD_DEVIATION 11.5 • n=72 Participants
Sex: Female, Male Female	6 Participants n=19 Participants	9 Participants n=18 Participants	7 Participants n=17 Participants	8 Participants n=18 Participants	30 Participants n=72 Participants
Sex: Female, Male Male	13 Participants n=19 Participants	9 Participants n=18 Participants	10 Participants n=17 Participants	10 Participants n=18 Participants	42 Participants n=72 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=19 Participants	0 Participants n=18 Participants	0 Participants n=17 Participants	0 Participants n=18 Participants	0 Participants n=72 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=19 Participants	18 Participants n=18 Participants	17 Participants n=17 Participants	18 Participants n=18 Participants	72 Participants n=72 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants	0 Participants n=18 Participants	0 Participants n=17 Participants	0 Participants n=18 Participants	0 Participants n=72 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=19 Participants	0 Participants n=18 Participants	0 Participants n=17 Participants	0 Participants n=18 Participants	0 Participants n=72 Participants
Race (NIH/OMB) Asian	0 Participants n=19 Participants	0 Participants n=18 Participants	0 Participants n=17 Participants	1 Participants n=18 Participants	1 Participants n=72 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=19 Participants	0 Participants n=18 Participants	0 Participants n=17 Participants	0 Participants n=18 Participants	0 Participants n=72 Participants
Race (NIH/OMB) Black or African American	0 Participants n=19 Participants	0 Participants n=18 Participants	0 Participants n=17 Participants	1 Participants n=18 Participants	1 Participants n=72 Participants
Race (NIH/OMB) White	19 Participants n=19 Participants	18 Participants n=18 Participants	17 Participants n=17 Participants	16 Participants n=18 Participants	70 Participants n=72 Participants
Race (NIH/OMB) More than one race	0 Participants n=19 Participants	0 Participants n=18 Participants	0 Participants n=17 Participants	0 Participants n=18 Participants	0 Participants n=72 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants	0 Participants n=18 Participants	0 Participants n=17 Participants	0 Participants n=18 Participants	0 Participants n=72 Participants
Ratio of phosphocreatine to adenosine triphosphate concentration	1.924 Ratio STANDARD_DEVIATION 0.354 • n=19 Participants • In the Placebo arm (Cohort B) there was one patient without baseline Cardiac magnetic resonance (CMR) measures.	1.719 Ratio STANDARD_DEVIATION 0.431 • n=17 Participants • In the Placebo arm (Cohort B) there was one patient without baseline Cardiac magnetic resonance (CMR) measures.	1.889 Ratio STANDARD_DEVIATION 0.407 • n=17 Participants • In the Placebo arm (Cohort B) there was one patient without baseline Cardiac magnetic resonance (CMR) measures.	1.896 Ratio STANDARD_DEVIATION 0.462 • n=18 Participants • In the Placebo arm (Cohort B) there was one patient without baseline Cardiac magnetic resonance (CMR) measures.	1.859 Ratio STANDARD_DEVIATION 0.413 • n=71 Participants • In the Placebo arm (Cohort B) there was one patient without baseline Cardiac magnetic resonance (CMR) measures.

PRIMARY outcome

Timeframe: At baseline and at week 12.

Population: Per protocol set (PPS): The primary endpoint analysis was performed using the per protocol (PP) set of patients with valid PCr/ATP ratio measurements available at baseline and Week 12, and no important protocol violation relevant to the primary endpoint.

Outcome measures

Outcome measures
Measure	Placebo Cohort A n=18 Participants Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF).	Placebo Cohort B n=11 Participants Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).	Empagliflozin 10mg Cohort A n=17 Participants Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF).	Empagliflozin 10mg Cohort B n=13 Participants Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).
Change From Baseline to Week 12 in PCr/ATP Ratio in the Resting State Measured by 31P Cardiac Magnetic Resonance Spectroscopy (MRS).	0.068 PCr / ATP Ratio Standard Error 0.114	0.259 PCr / ATP Ratio Standard Error 0.156	-0.179 PCr / ATP Ratio Standard Error 0.117	0.100 PCr / ATP Ratio Standard Error 0.143

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 3 other events

Deaths: 0 deaths

Empagliflozin 10mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=36 participants at risk Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF) and Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).	Empagliflozin 10mg n=35 participants at risk Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF) and Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).
Renal and urinary disorders Acute kidney injury	5.6% 2/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	2.9% 1/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Cardiac disorders Cardiac arrest	2.8% 1/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	0.00% 0/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Cardiac disorders Cardiac failure	2.8% 1/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	0.00% 0/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Cardiac disorders Cardiac failure congestive	5.6% 2/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	0.00% 0/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Eye disorders Glaucoma	2.8% 1/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	0.00% 0/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Infections and infestations Lower respiratory tract infection	2.8% 1/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	0.00% 0/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Metabolism and nutrition disorders Euglycaemic diabetic ketoacidosis	2.8% 1/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	0.00% 0/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	2.9% 1/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	2.8% 1/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	0.00% 0/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Nervous system disorders Syncope	2.8% 1/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	0.00% 0/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.

Other adverse events

Other adverse events
Measure	Placebo n=36 participants at risk Once a day oral administration of a single film-coated placebo tablet matching to empagliflozin for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF) and Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).	Empagliflozin 10mg n=35 participants at risk Once a day oral administration of a single 10 milligram (mg) film-coated empagliflozin tablet for 12 weeks. Cohort A: Heart failure (HF) with reduced ejection fraction (HFrEF) and Cohort B: Heart failure (HF) with preserved ejection fraction (HFpEF).
Infections and infestations Lower respiratory tract infection	5.6% 2/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	2.9% 1/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Infections and infestations Urinary tract infection	2.8% 1/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	8.6% 3/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	5.7% 2/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/36 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.	5.7% 2/35 • All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days. Treated set (TS): All randomised and treated patients were included in the safety analysis and safety summaries were presented by actual treatment received.

Additional Information

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