Dapagliflozin in Respiratory Failure in Patients With COVID-19

NCT04350593 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: D1690C00081ESR-20-20653
• Study Type: interventional
• Target: 1,250
• Locations: 7 countries
• Sites: 95

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.

Conditions

COVID-19

Keywords

sodium-glucose cotransporter-2 inhibitor (SGLT2i); dapagliflozin; COVID-19

Outcome Measures

Primary Outcomes (2)

• Prevention of COVID-19 Complications or Death: During the 30-day Treatment Period, Time to First Occurrence of New/Worsened Organ Dysfunction During Index Hospitalization or Death From Any Cause.

  Time to first occurrence of new/worsened organ dysfunction during index hospitalization or death from any cause. Event rates are presented as the number of subjects with event per 100 patient month (30 days) of follow-up. Unit of Measure: Patients with events per 100 patient-months (pt-mos) at risk. New/worsened organ dysfunction is defined as at least one of the following: * Respiratory decompensation requiring initiation of mechanical ventilation (includes invasive or non-invasive ventilation, CPAP, or BiPAP), and/or initiation of extracorporeal membrane oxygenation (ECMO) * New or worsening congestive heart failure * Requirement for vasopressor therapy and/or inotropic or mechanical circulatory support * Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest * Doubling of s-Creatinine or initiation of renal replacement therapy

  Randomization through Day 30

• Improving Clinical Recovery: Hierarchical Composite Outcome Measure Including Death From Any Cause Through Day 30, New/Worsened Organ Dysfunction, Clinical Status at Day 30 and Hospital Discharge Before Day 30 and Alive at Day 30.

  The number of patients experiencing improvement by day 30 compared with baseline (discharged from hospital without a worsening event and alive, or still in hospital without a worsening event and without oxygen support) in the hierarchical composite endpoint analysis. Hierarchical composite outcome measure includes: * Death from any cause through Day 30 * New/worsened organ dysfunction * Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction * Hospital discharge before Day 30 and alive at Day 30

  Randomization through Day 30

Secondary Outcomes (5)

• Time to Hospital Discharge

  Randomization through Day 30

• Total Number of Days Alive and Free From Respiratory Decompensation Requiring Initiation of Mechanical Ventilation (Includes Invasive or Non-invasive Ventilation, CPAP, or BiPAP)

  Randomization through Day 30

• Total Number of Days Alive, Not in the ICU, and Free From Respiratory Decompensation Requiring Initiation of Mechanical Ventilation (Includes Invasive or Non-invasive Ventilation, CPAP, or BiPAP)

  Randomization through Day 30

• Time to Composite of Acute Kidney Injury or Initiation of Renal Replacement Therapy, or Death From Any Cause

  Randomization through Day 30

• Time to Death From Any Cause

  Randomization through Day 30

Study Arms (2)

Dapagliflozin 10mg

ACTIVE COMPARATOR

Dapagliflozin 10 mg daily

Drug: Dapagliflozin 10 milligram (mg)

Placebo

PLACEBO COMPARATOR

Dapagliflozin matching placebo 10 mg daily

Drug: Placebo

Interventions

Dapagliflozin 10 milligram (mg) DRUG

Active Comparator: Dapagliflozin 10 mg

Also known as: Farxiga

Dapagliflozin 10mg

Placebo DRUG

Placebo Comparator

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent
• Male or female patients aged ≥18 years
• Currently hospitalized
• Hospital admission no more than 4 days prior to screening
• 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
• Chest radiography or computerized tomography (CT) findings that, in the opinion of the investigator, are consistent with coronavirus disease 2019 (COVID-19)
• Blood oxygen saturation (SpO2) ≥ 94% while receiving low-flow supplemental oxygen (5 liters or less)
• Medical history of at least one of the following:
• hypertension
• type 2 diabetes
• atherosclerotic cardiovascular disease
• heart failure (with either reduced or preserved left ventricular ejection fraction (LVEF))
• chronic kidney disease stage 3 to 4 (estimated glomerular filtration rate (eGFR) between 25 to 60 mL/min/1.73 m2)

You may not qualify if:

• Respiratory decompensation requiring mechanical ventilation (includes invasive or non invasive ventilation, continuous positive airway pressure (CPAP), or bilevel positive airway pressure (BiPAP))
• Expected need for mechanical ventilation (includes invasive or non-invasive ventilation, CPAP, or BiPAP) within the next 24 hours
• Expected survival of less than 24 hours at the time of presentation, in the judgement of the investigator
• eGFR \<25 mL/min/1.73 m2 or receiving renal replacement therapy/dialysis
• Systolic blood pressure \<95 mmHg and/or requirement for vasopressor treatment and/or inotropic or mechanical circulatory support at Screening
• History of type 1 diabetes mellitus
• History of diabetic ketoacidosis
• Currently receiving or has received in the last 14 days, experimental immune modulators and/or monoclonal antibody therapies for COVID-19
• 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
• 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.

Sponsors & Collaborators

• Saint Luke's Health System: lead
• St. Luke's Hospital, Kansas City, Missouri: collaborator
• AstraZeneca: collaborator
• Emerald Clinical Inc.: collaborator

Study Sites (95)

Heart Group of the Eastern Shore

Fairhope, Alabama, 36532, United States

Location

Baptist Hospital of Miami

Miami, Florida, 33176, United States

Location

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Loyola University

Maywood, Illinois, 60153, United States

Location

Ascension - St. Vincent

Indianapolis, Indiana, 46260, United States

Location

Lahey Health

Burlington, Massachusetts, 01805, United States

Location

McLaren Health Care

Auburn Hills, Michigan, 48326, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Saint Luke's Mid America Heart Institute

Kansas City, Missouri, 64111, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

St. Francis Hospital

Roslyn, New York, 11576, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17604, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Clinical Trials Network of Tennessee

Memphis, Tennessee, 38103, United States

Location

DHR Health Institute for Research and Development

Edinburg, Texas, 78539, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Sentara Healthcare

Norfolk, Virginia, 23507, United States

Location

Clínica de Especialidades Villa María

Villa María, Province of Córdoba, Argentina

Location

Fundación Favaloro

Buenos Aires, Argentina

Location

Hospital Español

Buenos Aires, Argentina

Location

Hospital Fernández

Buenos Aires, Argentina

Location

Hospital Pirovano

Buenos Aires, Argentina

Location

Hospital Santojanni

Buenos Aires, Argentina

Location

Sanatorio Anchorena

Buenos Aires, Argentina

Location

Sanatorio Güemes

Buenos Aires, Argentina

Location

Clínica Vélez Sarsfield

Córdoba, Argentina

Location

Hospital San Roque

Córdoba, Argentina

Location

Sanatorio Privado Duarte Quiros de Clinica Colombo S.A.

Córdoba, Argentina

Location

Centro de Pesquisa Dr. Marco Mota

Maceió, Alagoas, 57051-160, Brazil

Location

Hospital Maternidade São Vicente de Paulo

Barbalha, Ceará, 63180-000, Brazil

Location

Unimed de Fortaleza

Fortaleza, Ceará, 60055-172, Brazil

Location

Hospital de Messejana Dr Carlos Alberto Studart Gomes

Fortaleza, Ceará, 60840-285, Brazil

Location

Hospital Estadual Jayme dos Santos Neves

Serra, Espírito Santo, 29166-828, Brazil

Location

Hospital EMEC e Hospital da Cidade

Feira de Santana, Estado de Bahia, 44035-010, Brazil

Location

Hospital e Clínica São Roque

Ipiaú, Estado de Bahia, 45570-000, Brazil

Location

Hospital Regional Deputado Luis Eduardo Magalhães

Porto Seguro, Estado de Bahia, 45810-000, Brazil

Location

Hospital Cárdio Pulmonar

Salvador, Estado de Bahia, 41950-275, Brazil

Location

Hospital Coração do Brasil

Brasília, Federal District, 70390-700, Brazil

Location

Liga de Hipertensão Arterial

Goiânia, Goiás, 74690-900, Brazil

Location

Santa Casa de Misericórdia de Passos

Passos, Minas Gerais, 37904-020, Brazil

Location

Hospital São Domingos - Unimed Uberaba

Uberaba, Minas Gerais, 38025-440, Brazil

Location

PROCAPE

Recife, Pernambuco, 50100-060, Brazil

Location

Hospital Giselda Trigueiro

Natal, Rio Grande do Norte, 59037-170, Brazil

Location

Associação Dr. Bartholomeu Tacchini

Bento Gonçalves, Rio Grande do Sul, 95700-084, Brazil

Location

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, 99010-080, Brazil

Location

Irmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Hospital Mãe de Deus

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Hospital São José - Criciúma

Criciúma, Santa Catarina, 88811-250, Brazil

Location

IPEMI- Instituto de Pesquisas Médicas de Itajaí

Itajaí, Santa Catarina, 88301-303, Brazil

Location

Hospital Municipal São José

Joinville, Santa Catarina, 74605-050, Brazil

Location

Hospital Regional Hans Dieter Schmidt

Joinville, Santa Catarina, 89228-025, Brazil

Location

Centro de Pesquisa Clínica do Coração

Aracaju, Sergipe, 49055-530, Brazil

Location

Faculdade de Medicina de Botucatu, UNESP

Botucatu, São Paulo, 18618-687, Brazil

Location

Instituto de Pesquisa Clínica de Campinas

Campinas, São Paulo, 13060-904, Brazil

Location

Unimed Ribeirao Preto

Ribeirão Preto, São Paulo, 14110-000, Brazil

Location

Fundação do ABC (Hospital Estadual Mário Covas)

Santo André, São Paulo, 09090-790, Brazil

Location

Centro Integrado de Pesquisas

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Santa Casa de Votuporanga

Votuporanga, São Paulo, 15500-003, Brazil

Location

Fundação Pio XII

Barretos, 14784-400, Brazil

Location

Hospital Naval Marcílio Dias

Rio de Janeiro, 20725-090, Brazil

Location

Hospital Moriah

São Paulo, 04083-002, Brazil

Location

Hospital Santa Paula

São Paulo, 04556-100, Brazil

Location

InCor - Instituto do Coração do Hospital das Clínicas FMUSP

São Paulo, 05403-900, Brazil

Location

Halton Healthcare Services

Oakville, Ontario, Canada

Location

Lakeridge Health

Oshawa, Ontario, Canada

Location

CIMS Hospital Pvt. Ltd

Sola, Ahmedabad, 400022, India

Location

MIOT International Hospitals

Manapakkam, Chennai-89, India

Location

Sanjivani Super Speciality Hospital Pvt Ltd

Ahmedabad, Gujarat, 380015, India

Location

Lokmanya Tilak General Hospital

Mumbai, Maharashtra, 400022, India

Location

All India Institute of Medical Science

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Max Smart Super Speciality Hospital

Saket, New Delhi, 110017, India

Location

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

Saket, New Delhi, 110017, India

Location

Dayanand Medical College & Hospital

Ludhiana, Punjab, 141001, India

Location

Hospital del Prado

Acapulco, Mexico

Location

Icaro Investigaciones en Medicina

Chihuahua City, Mexico

Location

HG de Cuernavaca Dr. Jose G Parres

Cuernavaca, Mexico

Location

JM Research

Cuernavaca, Mexico

Location

Instituto de Investigaciones Aplicadas a la Neurosciencias

Durango, Mexico

Location

Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcade"

Guadalajara, Mexico

Location

Hospital San Javier

Guadalajara, Mexico

Location

Invesclinic MX

Guanajuato City, Mexico

Location

CIMEZAP

Jalisco, Mexico

Location

Hospital Medica Sur

Mexico City, Mexico

Location

Hospital Clinica Nova

Monterrey, Mexico

Location

Hospital San Jose TEC Salud

Monterrey, Mexico

Location

ECI Estudios Clinicos Internacionales

Puebla City, Mexico

Location

Hospital SMIQ

Querétaro, Mexico

Location

Investigacion Medica Sonora

Sonora, Mexico

Location

Sanatorio Santa Cruz de Toluca

Toluca, Mexico

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 40739638 DERIVED

• 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.

  PMID: 38770818 DERIVED

• 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.

  PMID: 35699910 DERIVED

• 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.

  PMID: 34302745 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: DARE-19 Global Project Manager
• Organization: Saint Luke's Hospital of Kansas City

DARE-19@saint-lukes.org

816-932-9858

Study Officials

• Mikhail Kosiborod, MD

  Saint Luke's Mid America Heart Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2020
• First Posted: April 17, 2020
• Study Start: April 22, 2020
• Primary Completion: March 31, 2021
• Study Completion: June 11, 2021
• Last Updated: June 10, 2022
• Results First Posted: April 13, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (22); CA (2); GB (1); ME (16); IN (8); BR (35); AR (11)