Randomized Controlled Trial

. 2020 Oct 1;35(10):1700-1711.

doi: 10.1093/ndt/gfaa234.

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

David C Wheeler¹, Bergur V Stefansson², Mikhail Batiushin³, Oleksandr Bilchenko⁴, David Z I Cherney^{5

6}, Glenn M Chertow^{7

8}, Walter Douthat⁹, Jamie P Dwyer¹⁰, Elizabeth Escudero¹¹, Roberto Pecoits-Filho^{12

13}, Hans Furuland¹⁴, José Luis Górriz¹⁵, Tom Greene¹⁶, Hermann Haller¹⁷, Fan Fan Hou¹⁸, Shin-Wook Kang¹⁹, Rey Isidto²⁰, Dinesh Khullar²¹, Patrick B Mark²², John J V McMurray²², Naoki Kashihara²³, Michal Nowicki²⁴, Frederik Persson²⁵, Ricardo Correa-Rotter²⁶, Peter Rossing^{25

27}, Robert D Toto²⁸, Kausik Umanath^{29

30}, Pham Van Bui³¹, István Wittmann³², Magnus Lindberg², C David Sjöström², Anna Maria Langkilde², Hiddo J L Heerspink³³

Affiliations

¹ Department of Renal Medicine, University College London, London, UK.
² Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
³ Department of Nephrology, Rostov State Medical University, Rostov, Russia.
⁴ Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine.
⁵ Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
⁶ Department of Medicine, Division of Nephrology, University of Toronto, Toronto, ON, Canada.
⁷ Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Department of Nephrology, Hospital Privado Universitario de Cordoba, Cordoba, Argentina.
¹⁰ Vanderbilt University Medical Center, Nashville, TN, USA.
¹¹ Division of Nephrology, Hospital Arzobispo Loayza, Cayetano Heredia University, Lima, Peru.
¹² School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, Brazil.
¹³ Arbor Research Collaborative for Health, Ann Arbor, MI, USA.
¹⁴ Department of Medical Sciences Renal Unit, Uppsala University Hospital, Uppsala, Sweden.
¹⁵ Department of Nephrology, University Clinic Hospital, INCLIVA, University of Valencia, Valencia, Spain.
¹⁶ Study Design and Biostatistics Center, University of Utah Health Sciences, Salt Lake City, UT, USA.
¹⁷ Hannover Medical School, Hanover, Germany.
¹⁸ Department of Medicine, Division of Nephrology, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China.
¹⁹ Department of Internal Medicine, Division of Nephrology, Yonsei University College of Medicine, Seoul, Korea.
²⁰ Healthlink Medical, Dental, Surgical Clinics and Diagnostics Center, Iloilo City, Philippines.
²¹ Department of Nephrology and Renal Transplant Medicine, Max Super Speciality Hospital, Saket, New Delhi, India.
²² Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
²³ Department of Nephrology and Hypertension, Kawasaki Medical School, Okayama, Japan.
²⁴ Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Łódź, Łódź, Poland.
²⁵ Steno Diabetes Center Copenhagen, Gentofte, Denmark.
²⁶ National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico.
²⁷ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
²⁸ Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
²⁹ Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, MI, USA.
³⁰ Division of Nephrology and Hypertension, Wayne State University, Detroit, MI, USA.
³¹ Pham Ngoc Thach Medicine University, Ho Chi Minh City, Vietnam.
³² Second Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, Hungary.
³³ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.

PMID: 32862232
PMCID: PMC7538235
DOI: 10.1093/ndt/gfaa234

Randomized Controlled Trial

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

David C Wheeler et al. Nephrol Dial Transplant. 2020.

. 2020 Oct 1;35(10):1700-1711.

doi: 10.1093/ndt/gfaa234.

Authors

Affiliations

¹ Department of Renal Medicine, University College London, London, UK.
² Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
³ Department of Nephrology, Rostov State Medical University, Rostov, Russia.
⁴ Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine.
⁵ Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
⁶ Department of Medicine, Division of Nephrology, University of Toronto, Toronto, ON, Canada.
⁷ Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Department of Nephrology, Hospital Privado Universitario de Cordoba, Cordoba, Argentina.
¹⁰ Vanderbilt University Medical Center, Nashville, TN, USA.
¹¹ Division of Nephrology, Hospital Arzobispo Loayza, Cayetano Heredia University, Lima, Peru.
¹² School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, Brazil.
¹³ Arbor Research Collaborative for Health, Ann Arbor, MI, USA.
¹⁴ Department of Medical Sciences Renal Unit, Uppsala University Hospital, Uppsala, Sweden.
¹⁵ Department of Nephrology, University Clinic Hospital, INCLIVA, University of Valencia, Valencia, Spain.
¹⁶ Study Design and Biostatistics Center, University of Utah Health Sciences, Salt Lake City, UT, USA.
¹⁷ Hannover Medical School, Hanover, Germany.
¹⁸ Department of Medicine, Division of Nephrology, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China.
¹⁹ Department of Internal Medicine, Division of Nephrology, Yonsei University College of Medicine, Seoul, Korea.
²⁰ Healthlink Medical, Dental, Surgical Clinics and Diagnostics Center, Iloilo City, Philippines.
²¹ Department of Nephrology and Renal Transplant Medicine, Max Super Speciality Hospital, Saket, New Delhi, India.
²² Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
²³ Department of Nephrology and Hypertension, Kawasaki Medical School, Okayama, Japan.
²⁴ Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Łódź, Łódź, Poland.
²⁵ Steno Diabetes Center Copenhagen, Gentofte, Denmark.
²⁶ National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico.
²⁷ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
²⁸ Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
²⁹ Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, MI, USA.
³⁰ Division of Nephrology and Hypertension, Wayne State University, Detroit, MI, USA.
³¹ Pham Ngoc Thach Medicine University, Ho Chi Minh City, Vietnam.
³² Second Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, Hungary.
³³ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.

PMID: 32862232
PMCID: PMC7538235
DOI: 10.1093/ndt/gfaa234

Abstract

Background: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials.

Methods: In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol).

Results: Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR).

Conclusions: Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.

Keywords: chronic kidney disease; dapagliflozin; randomized controlled clinical trial; sodium–glucose co-transporter-2 inhibitor.

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Figures

**FIGURE 1**
Proportion of participants in the eGFR and UACR categories.

**FIGURE 2**
Characteristics of study participants: (A) study participants by diabetes status, (B) investigator-reported causes of CKD in all study participants and (C) investigator-reported causes of CKD in study participants with T2D.

**FIGURE 3**
Number of participants with IgAN in clinical trials [18, 19].

See this image and copyright information in PMC

References

1. Zinman B, Wanner C, Lachin JM. et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117–2128 - PubMed
1. Neal B, Perkovic V, Mahaffey KW. et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644–657 - PubMed
1. Wiviott SD, Raz I, Bonaca MP. et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380: 347–357 - PubMed
1. Perkovic V, Jardine MJ, Neal B. et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295–2306 - PubMed
1. Heerspink HJ, Perkins BA, Fitchett DH. et al. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation 2016; 134: 752–772 - PubMed

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The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

Affiliations

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

Authors

Affiliations

Abstract

Figures

References

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Associated data

LinkOut - more resources

Full Text Sources

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Medical

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