January 26, 2017
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January 30, 2017
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July 6, 2020
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September 1, 2020
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September 1, 2020
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February 8, 2017
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July 17, 2019 (Final data collection date for primary outcome measure)
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Subjects Included in the Composite Endpoint of CV Death, Hospitalization Due to Heart Failure or Urgent Visit Due to Heart Failure. [ Time Frame: Up to 27.8 months. ] Primary efficacy
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Time to the first occurrence of any of the components of the composite: CV death or hospitalization for HF or an urgent HF visit. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
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- Subjects Included in the Composite Endpoint of CV Death or Hospitalization Due to Heart Failure. [ Time Frame: Up to 27.8 months. ]
Secondary
- Events Included in the Composite Endpoint of Recurrent Hospitalizations Due to Heart Failure and CV Death. [ Time Frame: Up to 27.8 months. ]
Secondary
- Change From Baseline in the KCCQ Total Symptom Score [ Time Frame: Baseline and 8 months or death before 8 months ]
KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The KCCQ total symptom score incorporates the symptom domains into a single score. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
- Subjects Included in the Composite Endpoint of ≥50% Sustained Decline in eGFR, ESRD or Renal Death. [ Time Frame: Up to 27.8 months. ]
Secondary
- Subjects Included in the Endpoint of All-cause Mortality. [ Time Frame: Up to 27.8 months. ]
Secondary
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- Time to the first occurrence of either of the components of the composite: CV death or hospitalization for HF. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
- Total number of (first and recurrent) HF hospitalizations and CV death. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
- Change from baseline measured at 8 months in the clinical summary score of the KCCQ, a specific HF patient reported outcome questionnaire. [ Time Frame: From randomization visit (day 0) up to 8 months (day 240) ]
- Time to the first occurrence of any of the components of the composite: ≥50% sustained decline in eGFR or reaching End Stage Renal Disease (ESRD) or renal death. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
End Stage Renal Disease (ESRD) is defined as;
- Sustained eGFR <15 ml/min/1.73m2 or,
- Chronic dialysis treatment or,
- Receiving a renal transplant
- Time to death from any cause. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
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Not Provided
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Not Provided
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Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure
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Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure With Reduced Ejection Fraction
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The purpose of this study is to evaluate the effect of dapagliflozin on the incidence of worsening heart failure or cardiovascular death in patients with chronic heart failure with reduced ejection fraction
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This is an international, multicentre, parallel group, event-driven, randomized, double-blind, placebo-controlled study in patients with chronic heart failure with reduced ejection fraction (HFrEF), evaluating the effect of dapagliflozin versus placebo, given once daily in addition to background regional standard of care therapy, for the prevention of cardiovascular (CV) death or reduction of heart failure (HF) events.
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
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- Experimental: Dapagliflozin
Patients will be randomized 1:1 to either dapagliflozin or placebo.
Intervention: Drug: Dapagliflozin
- Placebo Comparator: Placebo
Placebo matching dapagliflozin.
Intervention: Drug: Placebo
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- Yeoh SE, Dewan P, Jhund PS, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, Bengtsson O, Sjöstrand M, Langkilde AM, McMurray JJV; DAPA-HF Investigators and Committees. Patient Characteristics, Clinical Outcomes, and Effect of Dapagliflozin in Relation to Duration of Heart Failure: Is It Ever Too Late to Start a New Therapy? Circ Heart Fail. 2020 Dec;13(12):e007879. doi: 10.1161/CIRCHEARTFAILURE.120.007879. Epub 2020 Nov 9.
- Jhund PS, Solomon SD, Docherty KF, Heerspink HJL, Anand IS, Böhm M, Chopra V, de Boer RA, Desai AS, Ge J, Kitakaze M, Merkely B, O'Meara E, Schou M, Tereshchenko S, Verma S, Vinh PN, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Bengtsson O, Langkilde AM, Sjöstrand M, McMurray JJV. Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction: Results of DAPA-HF. Circulation. 2020 Oct 12. doi: 10.1161/CIRCULATIONAHA.120.050391. [Epub ahead of print]
- Docherty KF, Jhund PS, Anand I, Bengtsson O, Böhm M, de Boer RA, DeMets DL, Desai AS, Drozdz J, Howlett J, Inzucchi SE, Johanson P, Katova T, Køber L, Kosiborod MN, Langkilde AM, Lindholm D, Martinez FA, Merkely B, Nicolau JC, O'Meara E, Ponikowski P, Sabatine MS, Sjöstrand M, Solomon SD, Tereshchenko S, Verma S, McMurray JJV. Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF. Circulation. 2020 Oct 27;142(17):1623-1632. doi: 10.1161/CIRCULATIONAHA.120.047480. Epub 2020 Sep 4.
- Serenelli M, Böhm M, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, DeMets DL, Bengtsson O, Sjöstrand M, Langkilde AM, Anand IS, Chiang CE, Chopra VK, de Boer RA, Diez M, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Verma S, Docherty KF, Jhund PS, McMurray JJV. Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Eur Heart J. 2020 Sep 21;41(36):3402-3418. doi: 10.1093/eurheartj/ehaa496.
- Jackson AM, Dewan P, Anand IS, Bělohlávek J, Bengtsson O, de Boer RA, Böhm M, Boulton DW, Chopra VK, DeMets DL, Docherty KF, Dukát A, Greasley PJ, Howlett JG, Inzucchi SE, Katova T, Køber L, Kosiborod MN, Langkilde AM, Lindholm D, Ljungman CEA, Martinez FA, O'Meara E, Sabatine MS, Sjöstrand M, Solomon SD, Tereshchenko S, Verma S, Jhund PS, McMurray JJV. Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF. Circulation. 2020 Sep 15;142(11):1040-1054. doi: 10.1161/CIRCULATIONAHA.120.047077. Epub 2020 Jul 16. Erratum in: Circulation. 2020 Nov 17;142(20):e369.
- Solomon SD, Jhund PS, Claggett BL, Dewan P, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Inzucchi SE, Desai AS, Bengtsson O, Lindholm D, Sjostrand M, Langkilde AM, McMurray JJV. Effect of Dapagliflozin in Patients With HFrEF Treated With Sacubitril/Valsartan: The DAPA-HF Trial. JACC Heart Fail. 2020 Oct;8(10):811-818. doi: 10.1016/j.jchf.2020.04.008. Epub 2020 Jul 8.
- Dewan P, Solomon SD, Jhund PS, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, DeMets DL, Sabatine MS, Bengtsson O, Sjöstrand M, Langkilde AM, Anand IS, Bělohlávek J, Chopra VK, Dukát A, Kitakaze M, Merkely B, O'Meara E, Schou M, Vinh PN, McMurray JJV; DAPA-HF Investigators and Committees. Efficacy and safety of sodium-glucose co-transporter 2 inhibition according to left ventricular ejection fraction in DAPA-HF. Eur J Heart Fail. 2020 Jul;22(7):1247-1258. doi: 10.1002/ejhf.1867. Epub 2020 Jun 15.
- Petrie MC, Verma S, Docherty KF, Inzucchi SE, Anand I, Belohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett J, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Vinh PN, Schou M, Tereshchenko S, Køber L, Kosiborod MN, Langkilde AM, Martinez FA, Ponikowski P, Sabatine MS, Sjöstrand M, Solomon SD, Johanson P, Greasley PJ, Boulton D, Bengtsson O, Jhund PS, McMurray JJV. Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. JAMA. 2020 Apr 14;323(14):1353-1368. doi: 10.1001/jama.2020.1906.
- Kosiborod MN, Jhund PS, Docherty KF, Diez M, Petrie MC, Verma S, Nicolau JC, Merkely B, Kitakaze M, DeMets DL, Inzucchi SE, Køber L, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, Bengtsson O, Lindholm D, Niklasson A, Sjöstrand M, Langkilde AM, McMurray JJV. Effects of Dapagliflozin on Symptoms, Function, and Quality of Life in Patients With Heart Failure and Reduced Ejection Fraction: Results From the DAPA-HF Trial. Circulation. 2020 Jan 14;141(2):90-99. doi: 10.1161/CIRCULATIONAHA.119.044138. Epub 2019 Nov 17.
- Martinez FA, Serenelli M, Nicolau JC, Petrie MC, Chiang CE, Tereshchenko S, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Ponikowski P, Sabatine MS, DeMets DL, Dutkiewicz-Piasecka M, Bengtsson O, Sjöstrand M, Langkilde AM, Jhund PS, McMurray JJV. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age: Insights From DAPA-HF. Circulation. 2020 Jan 14;141(2):100-111. doi: 10.1161/CIRCULATIONAHA.119.044133. Epub 2019 Nov 17.
- McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19.
- McMurray JJV, DeMets DL, Inzucchi SE, Køber L, Kosiborod MN, Langkilde AM, Martinez FA, Bengtsson O, Ponikowski P, Sabatine MS, Sjöstrand M, Solomon SD; DAPA-HF Committees and Investigators. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019 Nov;21(11):1402-1411. doi: 10.1002/ejhf.1548. Epub 2019 Jul 15.
- Nassif ME, Kosiborod M. Effects of sodium glucose cotransporter type 2 inhibitors on heart failure. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:19-23. doi: 10.1111/dom.13678. Review.
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Completed
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4744
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4500
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July 17, 2019
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July 17, 2019 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Provision of signed informed consent prior to any study specific procedures
- Male or female, aged ≥18 years
- Established documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV), which has been present for at least 2 months
- LVEF≤40%
- Elevated NT-proBNP levels
- Patients should receive background standard of care for HFrEF and be treated according to locally recognized guidelines
- eGFR ≥30 mL/min/1.73 m^2 (CKD-EPI formula) at enrolment (visit 1)
Exclusion Criteria:
- Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
- Type 1 diabetes mellitus
- Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements either at visit 1 or visit 2
- Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment
- MI, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment
- Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization
- Implantation of a CRT within 12 weeks prior to enrolment or intent to implant a CRT device
- Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization
- HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease
- Symptomatic bradycardia or second or third degree heart block without a pacemaker
- Severe (eGFR <30 mL/min/1.73 m^2 by CKD-EPI), unstable or rapidly progressing renal disease at the time of randomization
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Sexes Eligible for Study: |
All |
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18 Years to 130 Years (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Argentina, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Germany, Hungary, India, Japan, Netherlands, Poland, Russian Federation, Slovakia, Sweden, Taiwan, United Kingdom, United States, Vietnam
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Czech Republic
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NCT03036124
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D1699C00001 2016-003897-41 ( EudraCT Number )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Not Provided
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AstraZeneca
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AstraZeneca
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Not Provided
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Not Provided
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AstraZeneca
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August 2020
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