NCT03030235: PRESERVED-HF

Dapagliflozin in PRESERVED Ejection Fraction Heart Failure

Completed Phase 4 Results posted Last updated 19 October 2022

What this trial tests

Phase 4 trial testing Dapagliflozin 10Mg Oral Tablet in Chronic Heart Failure With Preserved Systolic Function in 324 participants. Completed in 13 August 2021.

Timeline

1 March 2017

Primary endpoint
13 August 2021

13 August 2021

Quick facts

Lead sponsor	Saint Luke's Health System
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	324
Start date	1 March 2017
Primary completion	13 August 2021
Estimated completion	13 August 2021
Sites	26 locations across United States

Drugs / interventions tested

• Dapagliflozin 10Mg Oral Tablet
• Dapagliflozin matching placebo — full drug profile →

Conditions studied

• Chronic Heart Failure With Preserved Systolic Function — all drugs for Chronic Heart Failure With Preserved Systolic Function →

Sponsor

Saint Luke's Health System — full company profile →

Who can join

Adults 19 to 119, any sex, with Chronic Heart Failure With Preserved Systolic Function. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Effect of Dapagliflozin, as Compared With Placebo, on Heart Failure Related Health Status Using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Summary Score (KCCQ-CS) Primary · Baseline to Week 12

Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CS) at Week 12. The KCCQ is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the KCCQ-CS, a small but clinically meaningful change is considered to be ≥ 5 points. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline esti

Group	Value	95% CI
Dapagliflozin	68.6	66.2 – 71.0
Placebo	62.8	60.4 – 65.3

Effect of Dapagliflozin, as Compared With Placebo, on Heart Failure Related Health Status Using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) Secondary · Baseline to Week 12

Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) at Week 12. The KCCQ is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the KCCQ-OS, a small but clinically meaningful change is considered to be ≥ 5 points. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estim

Group	Value	95% CI
Dapagliflozin	68.9	66.5 – 71.3
Placebo	64.5	62.1 – 66.8

Effect of Dapagliflozin, as Compared With Placebo, on N-terminal Pro B-type Natriuretic Peptide (NTproBNP) Secondary · Baseline to Week 12

NTproBNP at Week 12. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.

Group	Value	95% CI
Dapagliflozin	733	673 – 799
Placebo	739	678 – 805

Effect of Dapagliflozin, as Compared With Placebo, on Brain Natriuretic Peptide (BNP) Secondary · Baseline to Week 12

BNP at Week 12. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.

Group	Value	95% CI
Dapagliflozin	147	136 – 160
Placebo	147	136 – 160

Effect of Dapagliflozin, as Compared With Placebo, on 6 Minute Walk Test Distance Secondary · Baseline to Week 12

6 minute walk test distance at 12 weeks. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.

Group	Value	95% CI
Dapagliflozin	262	252 – 272
Placebo	242	232 – 252

Effect of Dapagliflozin, as Compared With Placebo, on Hemoglobin A1c Secondary · Baseline to Week 12

Hemoglobin A1c at Week 12. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.

Group	Value	95% CI
Dapagliflozin	6.5	6.4 – 6.6
Placebo	6.6	6.5 – 6.7

Effect of Dapagliflozin, as Compared With Placebo, on the Proportion of Patients With a ≥ 5 Point Increase in KCCQ Clinical Summary Score (KCCQ-CS) and KCCQ Overall Summary Score (KCCQ-OS) Secondary · Baseline to Week 12

Proportion of patients with a ≥ 5 point increase in KCCQ-CS and KCCQ-OS at Week 12. The KCCQ is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For KCCQ-CS and KCCQ-OS, a small but clinically meaningful change is considered to be ≥ 5 points. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baselin

KCCQ-CS increase ≥ 5 points

Group	Value	95% CI
Dapagliflozin	69
Placebo	53

KCCQ-OS increase ≥ 5 points

Group	Value	95% CI
Dapagliflozin	75
Placebo	58

Effect of Dapagliflozin, as Compared With Placebo, on the Proportion of Patients With a ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide (NTproBNP) Secondary · Baseline to Week 12

Proportion of patients with a ≥ 20% decrease in NTproBNP at Week 12. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.

Group	Value	95% CI
Dapagliflozin	48
Placebo	44

Effect of Dapagliflozin, as Compared With Placebo, on Proportion of Patients With ≥ 5 Point Increase in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) and ≥ 20% Decrease in N-terminal Pro B-type Natriuretic Peptide(NTproBNP) Secondary · Baseline to Week 12

Proportion of patients with a ≥ 5 point increase in KCCQ-CS and a ≥ 20% decrease in NTproBNP at Week 12. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.

Group	Value	95% CI
Dapagliflozin	23
Placebo	15

Effect of Dapagliflozin, as Compared With Placebo, on Weight Secondary · Baseline to Week 12

Weight at Week 12. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.

Group	Value	95% CI
Dapagliflozin	101.3	100.9 – 101.8
Placebo	102.1	101.6 – 102.6

Effect of Dapagliflozin, as Compared With Placebo, on Systolic Blood Pressure Secondary · Baseline to Week 12

Systolic blood pressure at Week 12. Values have been adjusted for the corresponding baseline value, history of type 2 diabetes, sex, atrial fibrillation, baseline estimated glomerular filtration rate and left ventricular ejection fraction.

Group	Value	95% CI
Dapagliflozin	133	130 – 135
Placebo	133	131 – 136

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dapagliflozin

Serious: 31/162 (19%)

Deaths: 1/162

Placebo

Serious: 22/162 (14%)

Deaths: 2/162

Serious adverse events (64 terms)

Reaction	System	Dapagliflozin	Placebo
Exacerbation of Heart Failure	Cardiac disorders	—	—
Acute Kidney Injury	General disorders	—	—
Atrial Fibrillation	Cardiac disorders	—	—
Cellulitis	Infections and infestations	—	—
Chest Pain	General disorders	—	—
Covid-19	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Suicidal Ideation	General disorders	—	—
Volume Depletion	General disorders	—	—
Abdominal Wall Hematoma	Injury, poisoning and procedural complications	—	—
Acute Renal Failure	General disorders	—	—
Acute Respiratory Distress	General disorders	—	—
Acute Right Cerebellar Infarct	General disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Ascites of the Abdomen	Hepatobiliary disorders	—	—
Atrial Flutter	Cardiac disorders	—	—
Benign Paroxysmal Positional Vertigo	General disorders	—	—
Breast Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Clostridium Difficile	Infections and infestations	—	—
Critical Limb Ischemia	General disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Diverticulitis	Gastrointestinal disorders	—	—
Elective Watchman Device Implantation	Cardiac disorders	—	—
Elevated Troponin in the setting of Covid-19	General disorders	—	—
Exacerbation of Chronic Obstructive Pulmonary Disease	General disorders	—	—

Other adverse events (16 terms — click to expand)

Reaction	System	Dapagliflozin	Placebo
Volume Depletion	General disorders	—	—
Urgent Heart Failure Visit	Cardiac disorders	—	—
Nausea	General disorders	—	—
Leg pain	Musculoskeletal and connective tissue disorders	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—
Fatigue	General disorders	—	—
Neck Pain	Musculoskeletal and connective tissue disorders	—	—
Urinary Tract Infection	Infections and infestations	—	—
Gastrointestinal intolerance	Gastrointestinal disorders	—	—
Urinary frequency	General disorders	—	—
Rash	General disorders	—	—
Blurry vision	General disorders	—	—
Chest pain	General disorders	—	—
Shortness of Breath	General disorders	—	—
Foul smelling urine	General disorders	—	—
Sense of hopelessness	General disorders	—	—

Most-reported serious reactions: Exacerbation of Heart Failure, Acute Kidney Injury, Atrial Fibrillation, Cellulitis, Chest Pain, Covid-19, Sepsis, Suicidal Ideation.

Data from ClinicalTrials.gov NCT03030235 adverse events section.

Sponsor's own description

The primary purpose of this study is to evaluate the impact of dapagliflozin, as compared with placebo, on heart failure, disease specific biomarkers, symptoms, health status and quality of life in patients with chronic heart failure with preserved systolic function.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments.
   Guo J, Huang X, Dou L, Yan M, et al · · 2022 · cited 1019× · PMID 36522308 · DOI 10.1038/s41392-022-01251-0
2. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial.
   Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, et al · · 2021 · cited 439× · PMID 34711976 · DOI 10.1038/s41591-021-01536-x
3. Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials.
   Lytvyn Y, Bjornstad P, Udell JA, Lovshin JA, et al · · 2017 · cited 330× · PMID 29061576 · DOI 10.1161/circulationaha.117.030012
4. Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: A multinational observational study.
   Persson F, Nyström T, Jørgensen ME, Carstensen B, et al · · 2018 · cited 153× · PMID 28771923 · DOI 10.1111/dom.13077
5. Dapagliflozin: A Review in Type 2 Diabetes.
   Dhillon S. · · 2019 · cited 138× · PMID 31236801 · DOI 10.1007/s40265-019-01148-3
6. Medical Therapy for Heart Failure Caused by Ischemic Heart Disease.
   Elgendy IY, Mahtta D, Pepine CJ. · · 2019 · cited 131× · PMID 31120824 · DOI 10.1161/circresaha.118.313568
7. SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/ob^-/- mice.
   Adingupu DD, Göpel SO, Grönros J, Behrendt M, et al · · 2019 · cited 122× · PMID 30732594 · DOI 10.1186/s12933-019-0820-6
8. Chronic low-grade inflammation in heart failure with preserved ejection fraction.
   Mesquita T, Lin YN, Ibrahim A. · · 2021 · cited 77× · PMID 34382743 · DOI 10.1111/acel.13453