This is an international, multicenter, parallel-group, randomized, double-blind, placebo controlled, study in hospitalized adult patients with coronavirus disease 2019 (COVID-19) in the United States, Brazil, Mexico, Argentina, India, Canada, and United Kingdom. The study is evaluating the effect of dapagliflozin 10 milligrams versus placebo, given once daily for 30 days in addition to background local standard of care therapy, on reducing complications and all-cause mortality, or improving clinical recovery.
COVID-19 can lead to multiorgan failure, especially in high-risk patients. Dapagliflozin, a
sodium-glucose cotransporter-2 inhibitor (SGLT2i), favorably impacts many processes
dysregulated during acute illness such as COVID-19, has significant cardio- and
reno-protective benefits in cardiometabolic disease, and may provide similar organ protection
in COVID-19.
The study population will include hospitalized patients with respiratory manifestations of
COVID-19 of any duration, but without the need for mechanical ventilation. The eligible
patients should have risk factors for developing serious complications of COVID-19, including
hypertension, Type 2 diabetes, atherosclerotic cardiovascular disease, heart failure and/or
chronic kidney disease stage 3 to 4.
Patients will be treated for 30 days, with either dapagliflozin 10 milligrams daily or
placebo, each to be given in addition to the usual standard of care in the participating
hospital.
The study assessments include only those that are absolutely critical for ensuring the safety
of the patients, to measure efficacy outcomes, and collect biomarker data, so as not to place
too high a burden on the study personnel and to minimize additional risk of exposure to
severe acute respiratory syndrome coronavirus 2 (SARS CoV-2).
The dual primary efficacy endpoints of the study are time to first event of either
complications or death from any cause, and improved clinical recovery through 30 days of
follow-up. An extended follow-up period of 60 days (after the 30-day treatment period) is
included, in order to examine longer-term trajectory of recovery from COVID-19 among trial
participants.
The safety data will be monitored by an Independent Data and Safety Monitoring Committee.
Drug: Dapagliflozin 10 milligram (mg)
Active Comparator: Dapagliflozin 10 mg
Other Name: Farxiga
Drug: Placebo
Placebo Comparator
Inclusion Criteria:
1. Provision of informed consent
2. Male or female patients aged ≥18 years
3. Currently hospitalized
4. Hospital admission no more than 4 days prior to screening
5. Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by
laboratory testing within 10 days prior to screening, or strongly suspected SARS-CoV-2
infection on presentation
6. Chest radiography or computerized tomography (CT) findings that, in the opinion of the
investigator, are consistent with coronavirus disease 2019 (COVID-19)
7. Blood oxygen saturation (SpO2) ≥ 94% while receiving low-flow supplemental oxygen (5
liters or less)
8. Medical history of at least one of the following:
1. hypertension
2. type 2 diabetes
3. atherosclerotic cardiovascular disease
4. heart failure (with either reduced or preserved left ventricular ejection
fraction (LVEF))
5. chronic kidney disease stage 3 to 4 (estimated glomerular filtration rate (eGFR)
between 25 to 60 mL/min/1.73 m2)
Key Exclusion Criteria:
1. Respiratory decompensation requiring mechanical ventilation (includes invasive or non
invasive ventilation, continuous positive airway pressure (CPAP), or bilevel positive
airway pressure (BiPAP))
2. Expected need for mechanical ventilation (includes invasive or non-invasive
ventilation, CPAP, or BiPAP) within the next 24 hours
3. Expected survival of less than 24 hours at the time of presentation, in the judgement
of the investigator
4. eGFR <25 mL/min/1.73 m2 or receiving renal replacement therapy/dialysis
5. Systolic blood pressure <95 mmHg and/or requirement for vasopressor treatment and/or
inotropic or mechanical circulatory support at Screening
6. History of type 1 diabetes mellitus
7. History of diabetic ketoacidosis
8. Currently receiving or has received in the last 14 days, experimental immune
modulators and/or monoclonal antibody therapies for COVID-19
9. Current treatment with any sodium-glucose cotransporter-2 inhibitor (SGLT2i) (eg,
dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) or having received
treatment with any SGLT2i within 4 weeks prior to screening
10. Current participation in another interventional clinical trial (with an
investigational drug) that is not an observational registry
- Note that use of rescue therapies including immune modulators, monoclonal
antibody therapies, antiviral therapies, and other agents that are approved or
being used through open-label compassionate/expanded use programs or in
accordance with the local standard of care is permitted during the study.
Heart Group of the Eastern Shore
Fairhope, Alabama, United States
Baptist Hospital of Miami
Miami, Florida, United States
NorthShore University HealthSystem
Evanston, Illinois, United States
Loyola University
Maywood, Illinois, United States
Ascension - St. Vincent
Indianapolis, Indiana, United States
Lahey Health
Burlington, Massachusetts, United States
McLaren Health Care
Auburn Hills, Michigan, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Saint Luke's Mid America Heart Institute
Kansas City, Missouri, United States
Washington University School of Medicine
Saint Louis, Missouri, United States
Jacobi Medical Center
Bronx, New York, United States
SUNY Downstate Medical Center
Brooklyn, New York, United States
Maimonides Medical Center
Brooklyn, New York, United States
St. Francis Hospital
Roslyn, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
Lancaster General Hospital
Lancaster, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Clinical Trials Network of Tennessee
Memphis, Tennessee, United States
DHR Health Institute for Research and Development
Edinburg, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
Sentara Healthcare
Norfolk, Virginia, United States
Clínica de Especialidades Villa María
Villa María, Province Of Córdoba, Argentina
Fundación Favaloro
Buenos Aires, Argentina
Hospital Español
Buenos Aires, Argentina
Hospital Fernández
Buenos Aires, Argentina
Hospital Pirovano
Buenos Aires, Argentina
Hospital Santojanni
Buenos Aires, Argentina
Sanatorio Anchorena
Buenos Aires, Argentina
Sanatorio Güemes
Buenos Aires, Argentina
Clínica Vélez Sarsfield
Córdoba, Argentina
Hospital San Roque
Córdoba, Argentina
Sanatorio Privado Duarte Quiros de Clinica Colombo S.A.
Córdoba, Argentina
Centro de Pesquisa Dr. Marco Mota
Maceió, Alagoas, Brazil
Hospital EMEC e Hospital da Cidade
Feira de Santana, Bahia, Brazil
Hospital e Clínica São Roque
Ipiaú, Bahia, Brazil
Hospital Regional Deputado Luis Eduardo Magalhães
Porto Seguro, Bahia, Brazil
Hospital Cárdio Pulmonar
Salvador, Bahia, Brazil
Hospital Maternidade São Vicente de Paulo
Barbalha, Ceará, Brazil
Unimed de Fortaleza
Fortaleza, Ceará, Brazil
Hospital de Messejana Dr Carlos Alberto Studart Gomes
Fortaleza, Ceará, Brazil
Hospital Coração do Brasil
Brasília, Distrito Federal, Brazil
Hospital Estadual Jayme dos Santos Neves
Serra, Espírito Santo, Brazil
Liga de Hipertensão Arterial
Goiania, Goias, Brazil
Santa Casa de Misericórdia de Passos
Passos, Minas Gerais, Brazil
Hospital São Domingos - Unimed Uberaba
Uberaba, Minas Gerais, Brazil
PROCAPE
Recife, Pernambuco, Brazil
Hospital Giselda Trigueiro
Natal, Rio Grande Do Norte, Brazil
Associação Dr. Bartholomeu Tacchini
Bento Gonçalves, Rio Grande Do Sul, Brazil
Hospital São Vicente de Paulo
Passo Fundo, Rio Grande Do Sul, Brazil
Irmandade da Santa Casa de Misericórdia de Porto Alegre
Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Mãe de Deus
Porto Alegre, Rio Grande Do Sul, Brazil
Hospital São José - Criciúma
Criciuma, Santa Catarina, Brazil
IPEMI- Instituto de Pesquisas Médicas de Itajaí
Itajai, Santa Catarina, Brazil
Hospital Municipal São José
Joinville, Santa Catarina, Brazil
Hospital Regional Hans Dieter Schmidt
Joinville, Santa Catarina, Brazil
Centro de Pesquisa Clínica do Coração
Aracaju, Sergipe, Brazil
Faculdade de Medicina de Botucatu, UNESP
Botucatu, São Paulo, Brazil
Instituto de Pesquisa Clínica de Campinas
Campinas, São Paulo, Brazil
Unimed Ribeirao Preto
Ribeirão Preto, São Paulo, Brazil
Fundação do ABC (Hospital Estadual Mário Covas)
Santo André, São Paulo, Brazil
Centro Integrado de Pesquisas
São José do Rio Preto, São Paulo, Brazil
Santa Casa de Votuporanga
Votuporanga, São Paulo, Brazil
Fundação Pio XII
Barretos, Brazil
Hospital Naval Marcílio Dias
Rio de Janeiro, Brazil
Hospital Moriah
São Paulo, Brazil
Hospital Santa Paula
São Paulo, Brazil
InCor - Instituto do Coração do Hospital das Clínicas FMUSP
São Paulo, Brazil
Halton Healthcare Services
Oakville, Ontario, Canada
Lakeridge Health
Oshawa, Ontario, Canada
CIMS Hospital Pvt. Ltd
Sola, Ahmedabad, India
MIOT International Hospitals
Manapakkam, Chennai-89, India
All India Institute of Medical Science
New Delhi, Delhi, India
Sanjivani Super Speciality Hospital Pvt Ltd
Ahmedabad, Gujarat, India
Lokmanya Tilak General Hospital
Mumbai, Maharashtra, India
Max Smart Super Speciality Hospital
Saket, New Delhi, India
Max Super Speciality Hospital (A unit of Devki Devi Foundation)
Saket, New Delhi, India
Dayanand Medical College & Hospital
Ludhiāna, Punjab, India
Hospital del Prado
Acapulco, Mexico
Icaro Investigaciones en Medicina
Chihuahua, Mexico
HG de Cuernavaca Dr. Jose G Parres
Cuernavaca, Mexico
JM Research
Cuernavaca, Mexico
Instituto de Investigaciones Aplicadas a la Neurosciencias
Durango, Mexico
Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcade"
Guadalajara, Mexico
Hospital San Javier
Guadalajara, Mexico
Invesclinic MX
Guanajuato, Mexico
CIMEZAP
Jalisco, Mexico
Hospital Medica Sur
Mexico City, Mexico
Hospital Clinica Nova
Monterrey, Mexico
Hospital San Jose TEC Salud
Monterrey, Mexico
ECI Estudios Clinicos Internacionales
Puebla, Mexico
Hospital SMIQ
Queretaro, Mexico
Investigacion Medica Sonora
Sonora, Mexico
Sanatorio Santa Cruz de Toluca
Toluca, Mexico
Addenbrooke's Hospital
Cambridge, Cb2 0qq, United Kingdom
Mikhail Kosiborod, MD, Study Chair
Saint Luke's Mid America Heart Institute