Dapagliflozin in Respiratory Failure in Patients With COVID-19

NCT ID: NCT04350593

Last Updated: 2022-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-22
• Study Completion Date: 2021-06-11

Brief Summary

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.

Detailed Description

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dapagliflozin 10mg

Dapagliflozin 10 mg daily

Group Type: ACTIVE_COMPARATOR

Dapagliflozin 10 milligram (mg)

Intervention Type: DRUG

Active Comparator: Dapagliflozin 10 mg

Placebo

Dapagliflozin matching placebo 10 mg daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo Comparator

Interventions

Dapagliflozin 10 milligram (mg)

Active Comparator: Dapagliflozin 10 mg

Intervention Type: DRUG

Placebo

Placebo Comparator

Intervention Type: DRUG

Other Intervention Names

Farxiga

Eligibility Criteria

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)

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Luke's Hospital, Kansas City, Missouri

OTHER

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Emerald Clinical Inc.

INDUSTRY

Sponsor Role: collaborator

Saint Luke's Health System

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mikhail Kosiborod, MD

Role: STUDY_CHAIR

Saint Luke's Mid America Heart Institute

Locations

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

St Louis, Missouri, 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

Jacobi Medical Center

The Bronx, 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 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 Estadual Jayme dos Santos Neves

Serra, Espírito Santo, Brazil

Hospital EMEC e Hospital da Cidade

Feira de Santana, Estado de Bahia, Brazil

Hospital e Clínica São Roque

Ipiaú, Estado de Bahia, Brazil

Hospital Regional Deputado Luis Eduardo Magalhães

Porto Seguro, Estado de Bahia, Brazil

Hospital Cárdio Pulmonar

Salvador, Estado de Bahia, Brazil

Hospital Coração do Brasil

Brasília, Federal District, Brazil

Liga de Hipertensão Arterial

Goiânia, Goiás, 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

Criciúma, Santa Catarina, Brazil

IPEMI- Instituto de Pesquisas Médicas de Itajaí

Itajaí, 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

Sanjivani Super Speciality Hospital Pvt Ltd

Ahmedabad, Gujarat, India

Lokmanya Tilak General Hospital

Mumbai, Maharashtra, India

All India Institute of Medical Science

New Delhi, National Capital Territory of Delhi, India

Max Smart Super Speciality Hospital

Sāket, New Delhi, India

Max Super Speciality Hospital (A unit of Devki Devi Foundation)

Sāket, New Delhi, India

Dayanand Medical College & Hospital

Ludhiana, Punjab, India

Hospital del Prado

Acapulco, , Mexico

Icaro Investigaciones en Medicina

Chihuahua City, , 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 City, , 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 City, , Mexico

Hospital SMIQ

Querétaro, , Mexico

Investigacion Medica Sonora

Sonora, , Mexico

Sanatorio Santa Cruz de Toluca

Toluca, , Mexico

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Countries

United States; Argentina; Brazil; Canada; India; Mexico; United Kingdom

References

Abdel Jawad M, Furtado RHM, Esterline R, Oscarsson J, Gasparyan SB, Koch GG, Martinez F, Mukhtar O, Verma S, Langkilde AM, Ambery P, Patel S, Gosch K, Windsor SL, Soares RVP, Moia DDF, Aboudara M, Javaheri A, Saraiva JFK, Maia LN, Berwanger O, Sauer AJ, Kosiborod MN. Efficacy and safety of dapagliflozin in patients hospitalized with COVID-19 with and without type 2 diabetes: a prespecified analysis of the DARE-19 randomized trial. Cardiovasc Diabetol. 2025 Jul 30;24(1):307. doi: 10.1186/s12933-025-02875-6.

Reference Type: DERIVED

PMID: 40739638 (View on PubMed)

Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

Reference Type: DERIVED

PMID: 38770818 (View on PubMed)

Gasparyan SB, Buenconsejo J, Kowalewski EK, Oscarsson J, Bengtsson OF, Esterline R, Koch GG, Berwanger O, Kosiborod MN. Design and Analysis of Studies Based on Hierarchical Composite Endpoints: Insights from the DARE-19 Trial. Ther Innov Regul Sci. 2022 Sep;56(5):785-794. doi: 10.1007/s43441-022-00420-1. Epub 2022 Jun 14.

Reference Type: DERIVED

PMID: 35699910 (View on PubMed)

Kosiborod MN, Esterline R, Furtado RHM, Oscarsson J, Gasparyan SB, Koch GG, Martinez F, Mukhtar O, Verma S, Chopra V, Buenconsejo J, Langkilde AM, Ambery P, Tang F, Gosch K, Windsor SL, Akin EE, Soares RVP, Moia DDF, Aboudara M, Hoffmann Filho CR, Feitosa ADM, Fonseca A, Garla V, Gordon RA, Javaheri A, Jaeger CP, Leaes PE, Nassif M, Pursley M, Silveira FS, Barroso WKS, Lazcano Soto JR, Nigro Maia L, Berwanger O. Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2021 Sep;9(9):586-594. doi: 10.1016/S2213-8587(21)00180-7. Epub 2021 Jul 21.

Reference Type: DERIVED

PMID: 34302745 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ESR-20-20653

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

D1690C00081

Identifier Type: -

Identifier Source: org_study_id