COVID-19Phase 3VACURES-1NCT04539275
VA CoronavirUs Research and Efficacy Studies-1
A Phase 3 study testing Convalescent Plasma in people with COVID-19, run by VA Office of Research and Development at 24 sites in 2 countries.
Trial summary
The purpose of this study is to determine if treatment with convalescent plasma improves the clinical outcomes of Veterans who are hospitalized and require supplemental oxygen due to COVID-19. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Convalescent Plasma
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 24 sitesin 2 countries
- Study dates
- 16 Nov 2020to 30 Sep 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Veterans must meet all of the following criteria to be eligible to participate:
- Admitted to a participating VA clinical site with symptoms suggestive of SARS-CoV-2 infection.
- Participant (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
- Participant (or legally authorized representative) understands and agrees to comply with planned study procedures.
- Veteran 18 years of age at time of screening.
- Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or antigen test, as documented by either of the following:
Show all 9Show fewer
- (1)Reverse Transcription polymerase chain reaction (RT-PCR) or antigen positive (nasopharyngeal, oropharyngeal, saliva, lower respiratory) in sample collected 72 hours prior to screening; (2)RT-PCR or antigen positive in sample collected > 72 hours but 168 hours (i.e. 7 days) prior to screening, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc.), AND progressive disease suggestive of ongoing SARS-CoV-2 infection.
- 6.Requiring oxygen by nasal cannula or by face-mask as a new treatment (or if previously on home oxygen, at a liter flow at least 2 Lpm greater than home prescription), but not on humidified heated high-flow nasal cannula (HHHFNC) at 15 Lpm.
- 7.Can be randomized within 72 hours of hospital admission. 8.Agrees not to participate in another therapeutic clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29 without approval from the investigator(s). Taking part in other research studies, including those unrelated to SARS-CoV-2, without first discussing it with the investigators of this study may invalidate the results of this study, as well as that of the other study.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Respiratory failure requiring mechanical ventilation, non-invasive ventilation including continuous positive airway pressure (CPAP) (for an indication other than previously diagnosed sleep apnea and maintained on outpatient settings), or extra-corporeal membrane oxygenation or anticipated to require any of those treatments or to die within 24 hours.
- Anticipated discharge from the hospital or transfer to another hospital that is not a study site within 72 hours.
- History of previous transfusion reaction.
- Previously documented serum immunoglobulin A (IgA) deficiency (<7 mg/dL)
- Documented to have received convalescent plasma in the last 60 days.
Trial locations and contacts
24 sites in 2 countries.
24 sites in 2 countries
United States23 sites
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, 48105
Rocky Mountain Regional VA Medical Center, Aurora, CO
Aurora, Colorado, 80045
Birmingham VA Medical Center, Birmingham, AL
Birmingham, Alabama, 35233
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, 29401-5799
Louis Stokes VA Medical Center, Cleveland, OH
Cleveland, Ohio, 44106
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, 75216
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, 30033
John D. Dingell VA Medical Center, Detroit, MI
Detroit, Michigan, 48201
Durham VA Medical Center, Durham, NC
Durham, North Carolina, 27705
North Florida/South Georgia Veterans Health System, Gainesville, FL
Gainesville, Florida, 32608
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-5000
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, 77030
William S. Middleton Memorial Veterans Hospital, Madison, WI
Madison, Wisconsin, 53705
VA Southern Nevada Healthcare System, North Las Vegas, NV
North Las Vegas, Nevada, 89086
Oklahoma City VA Medical Center, Oklahoma City, OK
Oklahoma City, Oklahoma, 73104
Orlando VA Medical Center, Orlando, FL
Orlando, Florida, 32803
Phoenix VA Health Care System, Phoenix, AZ
Phoenix, Arizona, 85012
VA Portland Health Care System, Portland, OR
Portland, Oregon, 97239
Hunter Holmes McGuire VA Medical Center, Richmond, VA
Richmond, Virginia, 23249
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148
South Texas Health Care System, San Antonio, TX
San Antonio, Texas, 78229
James A. Haley Veterans' Hospital, Tampa, FL
Tampa, Florida, 33612
James J. Peters VA Medical Center, Bronx, NY
The Bronx, New York, 10468
Puerto Rico1 site
VA Caribbean Healthcare System, San Juan, PR
San Juan, 00921
About this study
Official title: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1)
The purpose of this study is to determine if treatment with convalescent plasma improves the clinical outcomes of Veterans who are hospitalized and require supplemental oxygen due to COVID-19.
Read the detailed description
As of August 25, 2020, SARS-Coronavirus 2 (SARS-CoV-2; COVID-19) infections are approaching 6 million persons and 180,000 deaths in the US. Of the 20% of patients admitted to hospital, up to half progress to ICU admission, respiratory failure or death. Prominent among these progressors are older men, particularly those with underlying comorbidities (e.g., hypertension, diabetes, lung, heart, kidney or liver disease, obesity and immunocompromised), all common among Veterans. There are no drugs or other therapeutics approved by the FDA to prevent or treat COVID-19 infection.
Convalescent plasma therapy is being used empirically, although only five of six small uncontrolled case series (total n=56) in SARS-CoV-23-8 and a recent study with non-randomized controls suggest improved selected clinical, virologic and laboratory outcomes; outcomes in another small randomized trial were equivocal. For other infections, such as influenza and Ebola virus, promising observational studies were not reliably confirmed by controlled trials. In multiple infections, use of convalescent plasma has been distinguished by its safety profile but not by the consistency of its benefit.
The current double-blind, placebo-controlled randomized clinical trial (RCT) is designed to determine definitively whether this intervention is effective in a population at high risk of complications and death from SARS-CoV-2 infection. The investigators compare the effect of convalescent plasma vs. saline placebo with a robust study design, adequate sample size and statistical and logistical rigor to assure that the interventions the investigators make to treat serious disease are well-validated to support its use or to move on to test other potentially safe and effective treatments.
This study is taking place at approximately 25 Veterans Affairs (VA) Medical Centers located across the US. A participant's involvement will last up to 33 days. The entire study, from the date the first person enters until the last participant is seen, is expected to last about 20 months.
Data collected for this study will be analyzed and stored at the Palo Alto Cooperative Studies Program Coordinating Center (CSPCC). After the study is completed, the de-identified, archived data will continue to be stored at the Palo Alto CSPCC, accessible for use by researchers including those outside of the study with an approved Data Use Agreement. The biospecimens collected in the study for current and future research will be kept at the VA Biorepository in Palo Alto, California unless otherwise specified. The biospecimens will be accessible for future research with an approved Sample Use Agreement. The VA Central Institutional Review Board (CIRB) will oversee the biorepository for this study. All samples will be destroyed by standard practice within 20 years of study completion. Sample destruction will be validated according to the Standard Operating Procedures of the VA Biorepository.
- Conditions
- COVID-19
- Being tested
- Convalescent Plasma, Masked Saline Placebo
- Keywords
- 2019 novel coronavirus disease, COVID-19 pandemic, COVID-19 virus infection, COVID-19 virus disease, Respiratory failure, Pneumonia, viral / therapy, Blood Component Transfusion, Severity of Illness Index, Survival Analysis, Treatment Outcome, Prospective Study, Humans, Adults, Male, Female, convalescent plasma, SARS CoV-2, COVID-19 convalescent plasma
- Medical subject headings
- COVID-19, Respiratory Insufficiency, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Convalescent PlasmaDrug
Also called COVID-19 Convalescent Plasma (CCP)
Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection.
Masked Saline PlaceboOther
Also called Normal Saline (NS)
0.9% saline solution will be used as the Masked Saline Placebo
| Study group | Role | What they receive |
|---|---|---|
| Convalescent Plasma | Experimental | The study intervention consists of intravenous administration of 200-500 mL of convalescent plasma administered in two equally divided doses, less than 12 hours apart. Receives: Drug: Convalescent Plasma |
| Masked Saline Placebo | Placebo comparator | The study intervention consists of intravenous administration of 200-500 mL of 0.9% saline administered in two equally divided doses, less than 12 hours apart. Receives: Other: Masked Saline Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants Developing Acute Hypoxemic Respiratory Failure or All-cause Death
Respiratory failure is defined as requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.
Measured: Day 1 through Day 28
Secondary outcomes (14)
Time (in Days) to Recovery
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the Modified World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement : 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy.
Measured: Day 1 through Day 28
Time (in Days) to Death or Respiratory Failure
Defined as the first day on which the subject died from any cause or had respiratory failure. Respiratory failure is defined by requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.
Measured: Day 1 through Day 28
Proportion of Patients Who Died From Any Cause, Had Respiratory Failure, or Required Humidified Heated High-flow Nasal Cannula (HHHFNC) at >= 15 Lpm
Defined as the proportion of subjects who died from any cause, had respiratory failure, or who required humidified heater high-flow cannula (HHHFNC) at >= 15 Lpm. Respiratory failure is defined by requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.
Measured: Day 1 through Day 28
Time (in Days) to Death, Respiratory Failure, or HHHFNC at >= 15 Lpm
Time to death or respiratory failure is defined as the first day on which the subject died from any cause, had respiratory failure (defined above), or who required HHHFNC at >= 15 Lpm.
Measured: Day 1 through Day 28
Number of Participants With 28-day All-cause Mortality
Death for Any Reason
Measured: Day 1 through Day 28
Time to an Improvement of at Least One Category Using an Ordinal Scale
Number of Days until the Modified WHO Clinical Status Improved by at Least One Category
Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO); 8) Death. The higher the score, the worse the outcome.
Measured: Up through 28 days.
Time to an Improvement of at Least Two Categories Using an Ordinal Scale
Number of Days until the Modified WHO Clinical Status Improved by at Least Two Categories
Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO; 8) Death. The higher the score, the worse the outcome.
Measured: Up through 28 days.
Participant's Clinical Status by Ordinal Scale
Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO; 8) Death. The higher the score, the worse the outcome.
Measured: Days 2, 4, 7, 11, 14, 21, and 28
Change in the Ordinal Scale From Baseline to Days 2, 4, 7, 11, 14, 21, and 28
Change in the Modified WHO Clinical Status
Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO; 8) Death. The higher the score, the worse the outcome.
Measured: From Baseline to Days 2, 4, 7, 11, 14, 21, and 28.
Categorical Change in the Ordinal Scale From Baseline to Days 2, 4, 7, 11, 14, 21, and 28
Categorical Change in the Modified WHO 8-point Ordinal Scale for Clinical Improvement
Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO; 8) Death. The higher the score, the worse the outcome.
Measured: From Baseline to Days 2, 4, 7, 11, 14, 21, and 28.
Time to Discharge or to a National Early Warning Score 2 (NEWS2) of <= 2 Maintained for at Least 22 Hours, Whichever Occurs First
Number of Days until Initial Hospitalization Discharge or (NEWS2 <= 2 Maintained for at Least 22 Hours)
The National Early Warning Score 2 (NEWS2) score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters and ranges from 0 to 20. The NEWS2 is being used as an efficacy measure. Higher scores mean a worse outcome.
Measured: Up through 28 days.
Change in National Early Warning Score 2 (NEWS2) From Day 1 (Baseline) to Days 2, 4, 7, 11, 15, and 29
Change in NEWS2
The National Early Warning Score 2 (NEWS2) has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters and ranges from 0 to 20. The NEWS2 is being used as an efficacy measure. Higher scores mean a worse outcome.
Measured: From Day 1 (baseline) to Days 2, 4, 7, 11, 15, and 29
Duration of Hospitalization
Number of Days Hospitalized During Initial Hospitalization
Measured: Day 1 through Day 28
Incidence of Discontinuation or Temporary Suspension of Study Product Administrations (for Any Reason)
Number of participants for whom study product administration was discontinued or temporarily suspended for any reason
Measured: Day 1 through Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2020
- Study start16 Nov 2020
- Primary completion30 Jun 2021
- Study completion30 Sep 2021
Why it stopped: DMC recommended early termination of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- There are two study treatment arms: convalescent plasma versus saline. Participants will be randomized in 1:1 ratio to these two arms.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Edward N. Janoff, MD, Study chair, Rocky Mountain Regional VA Medical Center, Aurora, CO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04539275
- Sponsor's protocol ID
- COVID19-8900-22
- Acronym
- VACURES-1
- Status last verified
- Sep 2022
- First submitted
- 27 Aug 2020
- Last updated
- 23 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Janoff EN, Shih MC, Donskey C, Belitskaya-Levy I, Brau N, Rodriguez-Barradas MC, Chan E, Zimmerman P, Miller EK, Vaughan LB, Daniel Markley J, Goldberg AM, Sriram P, Anzueto A, Uyeda L, Zehm L, Wills A, Hutchinson C, Jones L, Peterson D, Ringer RJ, Dumont L, Gleason T, Bonomo RA, Curtis JL, Brown ST; CURES-1 Trials Consortium. Impact of High-Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS-CoV-2 Infection: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1). J Med Virol. 2025 May;97(5):e70349. doi: 10.1002/jmv.70349.
PubMed 40400480Janoff EN, Brown ST, Belitskaya-Levy I, Curtis JL, Bonomo RA, Miller EK, Goldberg AM, Zehm L, Wills A, Hutchinson C, Dumont LJ, Gleason T, Shih MC; ADD Caitlin MS in CCTC website. Design of VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1): A double-blind, randomized placebo-controlled trial of COVID-19 convalescent plasma in hospitalized patients with early respiratory compromise. Contemp Clin Trials Commun. 2023 Jul 17;35:101190. doi: 10.1016/j.conctc.2023.101190. eCollection 2023 Oct.
PubMed 37560085Miller EK, Goldberg AM, Janoff EN, Brown ST, Curtis JL, Bonomo RA, Shih MC, Gleason TC. Designing and implementing methodology for double-blind, placebo-controlled clinical trials using blood products within the Department of Veterans Affairs. Clin Trials. 2022 Apr;19(2):137-145. doi: 10.1177/17407745211069703. Epub 2022 Mar 1.
PubMed 35229691
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1)
- ClinicalTrials.gov ID
- NCT04539275
- Acronym / sponsor ID
- VACURES-1 / COVID19-8900-22
- Conditions
- COVID-19
- Keywords
- 2019 novel coronavirus disease, COVID-19 pandemic, COVID-19 virus infection, COVID-19 virus disease, Respiratory failure, Pneumonia, viral / therapy, Blood Component Transfusion, Severity of Illness Index
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: DMC recommended early termination of enrollment
- Enrolment
- 75 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 16 Nov 2020 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 4 Sep 2020 (actual)
- Results
- Posted 10 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if treatment with convalescent plasma improves the clinical outcomes of Veterans who are hospitalized and require supplemental oxygen due to COVID-19.
Detailed description
As of August 25, 2020, SARS-Coronavirus 2 (SARS-CoV-2; COVID-19) infections are approaching 6 million persons and 180,000 deaths in the US. Of the 20% of patients admitted to hospital, up to half progress to ICU admission, respiratory failure or death. Prominent among these progressors are older men, particularly those with underlying comorbidities (e.g., hypertension, diabetes, lung, heart, kidney or liver disease, obesity and immunocompromised), all common among Veterans. There are no drugs or other therapeutics approved by the FDA to prevent or treat COVID-19 infection.
Convalescent plasma therapy is being used empirically, although only five of six small uncontrolled case series (total n=56) in SARS-CoV-23-8 and a recent study with non-randomized controls suggest improved selected clinical, virologic and laboratory outcomes; outcomes in another small randomized trial were equivocal. For other infections, such as influenza and Ebola virus, promising observational studies were not reliably confirmed by controlled trials. In multiple infections, use of convalescent plasma has been distinguished by its safety profile but not by the consistency of its benefit.
The current double-blind, placebo-controlled randomized clinical trial (RCT) is designed to determine definitively whether this intervention is effective in a population at high risk of complications and death from SARS-CoV-2 infection. The investigators compare the effect of convalescent plasma vs. saline placebo with a robust study design, adequate sample size and statistical and logistical rigor to assure that the interventions the investigators make to treat serious disease are well-validated to support its use or to move on to test other potentially safe and effective treatments.
This study is taking place at approximately 25 Veterans Affairs (VA) Medical Centers located across the US. A participant's involvement will last up to 33 days. The entire study, from the date the first person enters until the last participant is seen, is expected to last about 20 months.
Data collected for this study will be analyzed and stored at the Palo Alto Cooperative Studies Program Coordinating Center (CSPCC). After the study is completed, the de-identified, archived data will continue to be stored at the Palo Alto CSPCC, accessible for use by researchers including those outside of the study with an approved Data Use Agreement. The biospecimens collected in the study for current and future research will be kept at the VA Biorepository in Palo Alto, California unless otherwise specified. The biospecimens will be accessible for future research with an approved Sample Use Agreement. The VA Central Institutional Review Board (CIRB) will oversee the biorepository for this study. All samples will be destroyed by standard practice within 20 years of study completion. Sample destruction will be validated according to the Standard Operating Procedures of the VA Biorepository.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- There are two study treatment arms: convalescent plasma versus saline. Participants will be randomized in 1:1 ratio to these two arms.
| Arm | Type | Receives |
|---|---|---|
| Convalescent Plasma | Experimental | Drug: Convalescent PlasmaThe study intervention consists of intravenous administration of 200-500 mL of convalescent plasma administered in two equally divided doses, less than 12 hours apart. |
| Masked Saline Placebo | Placebo comparator | Other: Masked Saline PlaceboThe study intervention consists of intravenous administration of 200-500 mL of 0.9% saline administered in two equally divided doses, less than 12 hours apart. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Admitted to a participating VA clinical site with symptoms suggestive of SARS-CoV-2 infection.
- Participant (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
- Participant (or legally authorized representative) understands and agrees to comply with planned study procedures.
- Veteran 18 years of age at time of screening.
- Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or antigen test, as documented by either of the following:
Key exclusion criteria (6 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Respiratory failure requiring mechanical ventilation, non-invasive ventilation including continuous positive airway pressure (CPAP) (for an indication other than previously diagnosed sleep apnea and maintained on outpatient settings), or extra-corporeal membrane oxygenation or anticipated to require any of those treatments or to die within 24 hours.
- Anticipated discharge from the hospital or transfer to another hospital that is not a study site within 72 hours.
- History of previous transfusion reaction.
- Previously documented serum immunoglobulin A (IgA) deficiency (<7 mg/dL)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Convalescent PlasmaAlso: COVID-19 Convalescent Plasma (CCP)Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection. | Drug | Convalescent Plasma |
| Masked Saline PlaceboAlso: Normal Saline (NS)0.9% saline solution will be used as the Masked Saline Placebo | Other | Masked Saline Placebo |
Primary outcome
Proportion of Participants Developing Acute Hypoxemic Respiratory Failure or All-cause Death
Time frame: Day 1 through Day 28
Respiratory failure is defined as requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.
14 secondary outcomes
Time (in Days) to Recovery
Time frame: Day 1 through Day 28
Time (in Days) to Death or Respiratory Failure
Time frame: Day 1 through Day 28
Proportion of Patients Who Died From Any Cause, Had Respiratory Failure, or Required Humidified Heated High-flow Nasal Cannula (HHHFNC) at >= 15 Lpm
Time frame: Day 1 through Day 28
Time (in Days) to Death, Respiratory Failure, or HHHFNC at >= 15 Lpm
Time frame: Day 1 through Day 28
Number of Participants With 28-day All-cause Mortality
Time frame: Day 1 through Day 28
Time to an Improvement of at Least One Category Using an Ordinal Scale
Time frame: Up through 28 days.
Time to an Improvement of at Least Two Categories Using an Ordinal Scale
Time frame: Up through 28 days.
Participant's Clinical Status by Ordinal Scale
Time frame: Days 2, 4, 7, 11, 14, 21, and 28
Change in the Ordinal Scale From Baseline to Days 2, 4, 7, 11, 14, 21, and 28
Time frame: From Baseline to Days 2, 4, 7, 11, 14, 21, and 28.
Categorical Change in the Ordinal Scale From Baseline to Days 2, 4, 7, 11, 14, 21, and 28
Time frame: From Baseline to Days 2, 4, 7, 11, 14, 21, and 28.
Time to Discharge or to a National Early Warning Score 2 (NEWS2) of <= 2 Maintained for at Least 22 Hours, Whichever Occurs First
Time frame: Up through 28 days.
Change in National Early Warning Score 2 (NEWS2) From Day 1 (Baseline) to Days 2, 4, 7, 11, 15, and 29
Time frame: From Day 1 (baseline) to Days 2, 4, 7, 11, 15, and 29
Duration of Hospitalization
Time frame: Day 1 through Day 28
Incidence of Discontinuation or Temporary Suspension of Study Product Administrations (for Any Reason)
Time frame: Day 1 through Day 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40400480Janoff EN, Shih MC, Donskey C, Belitskaya-Levy I, Brau N, Rodriguez-Barradas MC, Chan E, Zimmerman P, Miller EK, Vaughan LB, Daniel Markley J, Goldberg AM, Sriram P, Anzueto A, Uyeda L, Zehm L, Wills A, Hutchinson C, Jones L, Peterson D, Ringer RJ, Dumont L, Gleason T, Bonomo RA, Curtis JL, Brown ST; CURES-1 Trials Consortium. Impact of High-Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS-CoV-2 Infection: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1). J Med Virol. 2025 May;97(5):e70349. doi: 10.1002/jmv.70349.
- Derived from this study: PubMed 37560085Janoff EN, Brown ST, Belitskaya-Levy I, Curtis JL, Bonomo RA, Miller EK, Goldberg AM, Zehm L, Wills A, Hutchinson C, Dumont LJ, Gleason T, Shih MC; ADD Caitlin MS in CCTC website. Design of VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1): A double-blind, randomized placebo-controlled trial of COVID-19 convalescent plasma in hospitalized patients with early respiratory compromise. Contemp Clin Trials Commun. 2023 Jul 17;35:101190. doi: 10.1016/j.conctc.2023.101190. eCollection 2023 Oct.
- Derived from this study: PubMed 35229691Miller EK, Goldberg AM, Janoff EN, Brown ST, Curtis JL, Bonomo RA, Shih MC, Gleason TC. Designing and implementing methodology for double-blind, placebo-controlled clinical trials using blood products within the Department of Veterans Affairs. Clin Trials. 2022 Apr;19(2):137-145. doi: 10.1177/17407745211069703. Epub 2022 Mar 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward N. Janoff, MD study chair
Rocky Mountain Regional VA Medical Center, Aurora, CO
24 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Convalescent Plasma in people with COVID-19, run by VA Office of Research and Development at 24 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Developing Acute Hypoxemic Respiratory Failure or All-cause Death (time frame: Day 1 through Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04539275, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2022.