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DMC recommended early termination of enrollment
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Convalescent Plasma | Drug | Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 through Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 through Day 28 |
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Inclusion Criteria:
Veterans must meet all of the following criteria to be eligible to participate:
(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.
Exclusion Criteria:
An individual who meets any of the following criteria will be excluded from participation in this study:
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| Name | Affiliation | Role |
|---|---|---|
| Edward N. Janoff, MD | Rocky Mountain Regional VA Medical Center, Aurora, CO | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham VA Medical Center, Birmingham, AL | Birmingham | Alabama | 35233 | United States | ||
| Phoenix VA Health Care System, Phoenix, AZ |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40400480 | Derived | 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. | |
| 37560085 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Convalescent Plasma | 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. Convalescent Plasma: Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 22, 2021 |
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There are two study treatment arms: convalescent plasma versus saline. Participants will be randomized in 1:1 ratio to these two arms.
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The participants, site investigators, clinical prescribers, site coordinators, and most other individuals involved in this study will be blinded to the treatment assignment.
Furthermore, the blind will not routinely be broken in order to select post-study, pharmacologic treatment for SARS-CoV-2 infection administered by clinical healthcare providers.
|
| Masked Saline Placebo | Other | 0.9% saline solution will be used as the Masked Saline Placebo |
|
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| 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. | 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. | 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. | Day 1 through Day 28 |
| Number of Participants With 28-day All-cause Mortality | Death for Any Reason | 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. | 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. | 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. | 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. | 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. | 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. | 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. | From Day 1 (baseline) to Days 2, 4, 7, 11, 15, and 29 |
| Duration of Hospitalization | Number of Days Hospitalized During Initial Hospitalization | 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 | Day 1 through Day 3 |
| Phoenix |
| Arizona |
| 85012 |
| United States |
| Rocky Mountain Regional VA Medical Center, Aurora, CO | Aurora | Colorado | 80045 | United States |
| North Florida/South Georgia Veterans Health System, Gainesville, FL | Gainesville | Florida | 32608 | United States |
| Orlando VA Medical Center, Orlando, FL | Orlando | Florida | 32803 | United States |
| James A. Haley Veterans' Hospital, Tampa, FL | Tampa | Florida | 33612 | United States |
| Atlanta VA Medical and Rehab Center, Decatur, GA | Decatur | Georgia | 30033 | United States |
| Edward Hines Jr. VA Hospital, Hines, IL | Hines | Illinois | 60141-5000 | United States |
| VA Ann Arbor Healthcare System, Ann Arbor, MI | Ann Arbor | Michigan | 48105 | United States |
| John D. Dingell VA Medical Center, Detroit, MI | Detroit | Michigan | 48201 | United States |
| VA Southern Nevada Healthcare System, North Las Vegas, NV | North Las Vegas | Nevada | 89086 | United States |
| James J. Peters VA Medical Center, Bronx, NY | The Bronx | New York | 10468 | United States |
| Durham VA Medical Center, Durham, NC | Durham | North Carolina | 27705 | United States |
| Louis Stokes VA Medical Center, Cleveland, OH | Cleveland | Ohio | 44106 | United States |
| Oklahoma City VA Medical Center, Oklahoma City, OK | Oklahoma City | Oklahoma | 73104 | United States |
| VA Portland Health Care System, Portland, OR | Portland | Oregon | 97239 | United States |
| Ralph H. Johnson VA Medical Center, Charleston, SC | Charleston | South Carolina | 29401-5799 | United States |
| VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX | Dallas | Texas | 75216 | United States |
| Michael E. DeBakey VA Medical Center, Houston, TX | Houston | Texas | 77030 | United States |
| South Texas Health Care System, San Antonio, TX | San Antonio | Texas | 78229 | United States |
| VA Salt Lake City Health Care System, Salt Lake City, UT | Salt Lake City | Utah | 84148 | United States |
| Hunter Holmes McGuire VA Medical Center, Richmond, VA | Richmond | Virginia | 23249 | United States |
| William S. Middleton Memorial Veterans Hospital, Madison, WI | Madison | Wisconsin | 53705 | United States |
| VA Caribbean Healthcare System, San Juan, PR | San Juan | 00921 | Puerto Rico |
| Derived |
| Janoff 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. |
| 35229691 | Derived | Miller 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. |
| FG001 |
| Masked Saline Placebo |
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. Masked Saline Placebo: 0.9% saline solution will be used as the Masked Saline Placebo |
| Received Study Product |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Convalescent Plasma | 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. Convalescent Plasma: Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection. |
| BG001 | Masked Saline Placebo | 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. Masked Saline Placebo: 0.9% saline solution will be used as the Masked Saline Placebo |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Clinical Status | Count of Participants | Participants |
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| 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. | Median | Inter-Quartile Range | units on a scale |
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| White Blood Cell (WBC) Count | Median | Inter-Quartile Range | K cells/mcL |
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| Neutrophil Count | Lab test was not done for 2 participants in the Masked Saline Placebo group. | Median | Inter-Quartile Range | K cells/mcL |
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| Total Lymphocyte Count | Lab test was not done for 2 participants in the Masked Saline Placebo group. | Median | Inter-Quartile Range | K cells/mcL |
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| Hemoglobin | Median | Inter-Quartile Range | g/dL |
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| Platelets | Median | Inter-Quartile Range | K cells/mcL |
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| Creatinine | Median | Inter-Quartile Range | mg/dL |
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| Glucose | Median | Inter-Quartile Range | mg/dL |
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| Alanine Transaminase (ALT/SGPT) | Lab test was not done for 1 participant in the Convalescent Plasma group. | Median | Inter-Quartile Range | U/L |
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| Aspartate Transaminase (AST/SGOT) | Lab test was not done for 1 participant in the Convalescent Plasma group. | Median | Inter-Quartile Range | U/L |
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| International Normalized Ratio (INR) | Lab test was not done for 4 participants in the Convalescent Plasma group and 3 participants in the Masked Saline Placebo group. | Median | Inter-Quartile Range | unitless |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | The primary outcome cannot be determined for 5 participants (4 in Convalescent Plasma, and 1 in Masked Saline Placebo) who terminated early from the study | Posted | Count of Participants | Participants | Day 1 through Day 28 |
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| Secondary | 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. | All randomized participants are included in this analysis. | Posted | Median | Inter-Quartile Range | Days | Day 1 through Day 28 |
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| Secondary | 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. | All randomized participants are included in the analysis | Posted | Median | Inter-Quartile Range | days | Day 1 through Day 28 |
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| Secondary | 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. | This secondary outcome cannot be determined for 5 participants (4 in Convalescent Plasma, and 1 in Masked Saline Placebo) who terminated early from the study | Posted | Count of Participants | Participants | Day 1 through Day 28 |
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| Secondary | 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. | All randomized participants were included in this analysis. | Posted | Median | Inter-Quartile Range | days | Day 1 through Day 28 |
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| Secondary | Number of Participants With 28-day All-cause Mortality | Death for Any Reason | This secondary outcome cannot be determined for 5 participants (4 in Convalescent Plasma, and 1 in Masked Saline Placebo) who terminated early from the study | Posted | Count of Participants | Participants | Day 1 through Day 28 |
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| Secondary | 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. | All randomized participants were included in this analysis. | Posted | Median | Inter-Quartile Range | days | Up through 28 days. |
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| Secondary | 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. | All randomized participants were included in this analysis. | Posted | Median | Inter-Quartile Range | days | Up through 28 days. |
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| Secondary | 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. | This secondary outcome cannot be determined for 3 participants (3 in Convalescent Plasma, and 0 in Masked Saline Placebo) who terminated on the day of randomization. | Posted | Count of Participants | Participants | Days 2, 4, 7, 11, 14, 21, and 28 |
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| Secondary | 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. | This secondary outcome cannot be determined for 3 participants (3 in Convalescent Plasma, and 0 in Masked Saline Placebo) who terminated on the day of randomization. | Posted | Median | Full Range | units on a scale | From Baseline to Days 2, 4, 7, 11, 14, 21, and 28. |
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| Secondary | 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. | This secondary outcome cannot be determined for 3 participants (3 in Convalescent Plasma, and 0 in Masked Saline Placebo) who terminated on the day of randomization. | Posted | Count of Participants | Participants | From Baseline to Days 2, 4, 7, 11, 14, 21, and 28. |
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| Secondary | 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. | All randomized participants were included in this analysis. | Posted | Median | Inter-Quartile Range | days | Up through 28 days. |
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| Secondary | 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. | This secondary outcome cannot be determined for 3 participants (3 in Convalescent Plasma, and 0 in Masked Saline Placebo) who terminated on the day of randomization. | Posted | Median | Inter-Quartile Range | score on a scale | From Day 1 (baseline) to Days 2, 4, 7, 11, 15, and 29 |
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| Secondary | Duration of Hospitalization | Number of Days Hospitalized During Initial Hospitalization | This secondary outcome cannot be determined for 3 participants (3 in Convalescent Plasma, and 0 in Masked Saline Placebo) who terminated early on the day of randomization. | Posted | Median | Inter-Quartile Range | days | Day 1 through Day 28 |
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| Secondary | 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 | 3 participants in the Convalescent Plasma group withdrew from the study prior to study product administration. | Posted | Count of Participants | Participants | Day 1 through Day 3 |
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|
28 days
The study requires reporting of the following types of events :
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Convalescent Plasma | 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. Convalescent Plasma: Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection. | 3 | 35 | 8 | 35 | 5 | 35 |
| EG001 | Masked Saline Placebo | 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. Masked Saline Placebo: 0.9% saline solution will be used as the Masked Saline Placebo | 4 | 40 | 5 | 40 | 9 | 40 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Myocardial Infarction | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Supraventricular Tachycardia | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| COVID-19 Pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Diabetic Foot Infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Septic Shock | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Electrocardiogram ST Segment Elevation | Investigations | MedDRA 23.1 | Systematic Assessment |
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| Acute Kidney Injury | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Oxygen Consumption Increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Fluid Overload | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Intensive Care | Surgical and medical procedures | MedDRA 23.1 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypertensive Urgency | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lisa Zehm, Project Manager | Palo Alto Cooperative Studies Program Coordinating Center | (650)493-5000 | 28805 | lisa.zehm@va.gov |
| May 25, 2022 |
| Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 18, 2021 | Jul 9, 2021 | ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D012131 | Respiratory Insufficiency |
| D011014 | Pneumonia |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000093522 | COVID-19 Serotherapy |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D019264 | Adoptive Transfer |
| D007116 | Immunization, Passive |
| D007114 | Immunization |
| D007167 | Immunotherapy |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D007158 | Immunologic Techniques |
| D008919 | Investigative Techniques |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
| Between 18 and 65 years |
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| >=65 years |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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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.
Masked Saline Placebo: 0.9% saline solution will be used as the Masked Saline Placebo
|
|
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. Masked Saline Placebo: 0.9% saline solution will be used as the Masked Saline Placebo |
|
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Ambulatory, limitation of activity and/or home oxygen |
|
| Hospitalized Mild Disease, no oxygen therapy |
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| Hospitalized Mild Disease, oxygen by mask or nasal prong |
|
| Hospitalized Severe Disease, humidified high-flow oxygen |
|
| Hospitalized Severe Disease, non-invasive ventilation |
|
| Hospitalized Severe Disease, intubation and mechanical ventilation |
|
| Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO |
|
| Death |
|
| Ambulatory, limitation of activity and/or home oxygen |
|
| Hospitalized Mild Disease, no oxygen therapy |
|
| Hospitalized Mild Disease, oxygen by mask or nasal prong |
|
| Hospitalized Severe Disease, humidified high-flow oxygen |
|
| Hospitalized Severe Disease, non-invasive ventilation |
|
| Hospitalized Severe Disease, intubation and mechanical ventilation |
|
| Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO |
|
| Death |
|
| Ambulatory, limitation of activity and/or home oxygen |
|
| Hospitalized Mild Disease, no oxygen therapy |
|
| Hospitalized Mild Disease, oxygen by mask or nasal prong |
|
| Hospitalized Severe Disease, humidified high-flow oxygen |
|
| Hospitalized Severe Disease, non-invasive ventilation |
|
| Hospitalized Severe Disease, intubation and mechanical ventilation |
|
| Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO |
|
| Death |
|
| Ambulatory, limitation of activity and/or home oxygen |
|
| Hospitalized Mild Disease, no oxygen therapy |
|
| Hospitalized Mild Disease, oxygen by mask or nasal prong |
|
| Hospitalized Severe Disease, humidified high-flow oxygen |
|
| Hospitalized Severe Disease, non-invasive ventilation |
|
| Hospitalized Severe Disease, intubation and mechanical ventilation |
|
| Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO |
|
| Death |
|
| Ambulatory, limitation of activity and/or home oxygen |
|
| Hospitalized Mild Disease, no oxygen therapy |
|
| Hospitalized Mild Disease, oxygen by mask or nasal prong |
|
| Hospitalized Severe Disease, humidified high-flow oxygen |
|
| Hospitalized Severe Disease, non-invasive ventilation |
|
| Hospitalized Severe Disease, intubation and mechanical ventilation |
|
| Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO |
|
| Death |
|
| Ambulatory, limitation of activity and/or home oxygen |
|
| Hospitalized Mild Disease, no oxygen therapy |
|
| Hospitalized Mild Disease, oxygen by mask or nasal prong |
|
| Hospitalized Severe Disease, humidified high-flow oxygen |
|
| Hospitalized Severe Disease, non-invasive ventilation |
|
| Hospitalized Severe Disease, intubation and mechanical ventilation |
|
| Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO |
|
| Death |
|
| 3 Point Improvement |
|
| 2 Point Improvement |
|
| 1 Point Improvement |
|
| No Change |
|
| 1 Point Worsening |
|
| 2 Point Worsening |
|
| 3 Point Worsening |
|
| 4 Point Worsening |
|
| 3 Point Improvement |
|
| 2 Point Improvement |
|
| 1 Point Improvement |
|
| No Change |
|
| 1 Point Worsening |
|
| 2 Point Worsening |
|
| 3 Point Worsening |
|
| 4 Point Worsening |
|
| 3 Point Improvement |
|
| 2 Point Improvement |
|
| 1 Point Improvement |
|
| No Change |
|
| 1 Point Worsening |
|
| 2 Point Worsening |
|
| 3 Point Worsening |
|
| 4 Point Worsening |
|
| 3 Point Improvement |
|
| 2 Point Improvement |
|
| 1 Point Improvement |
|
| No Change |
|
| 1 Point Worsening |
|
| 2 Point Worsening |
|
| 3 Point Worsening |
|
| 4 Point Worsening |
|
| 3 Point Improvement |
|
| 2 Point Improvement |
|
| 1 Point Improvement |
|
| No Change |
|
| 1 Point Worsening |
|
| 2 Point Worsening |
|
| 3 Point Worsening |
|
| 4 Point Worsening |
|
| 3 Point Improvement |
|
| 2 Point Improvement |
|
| 1 Point Improvement |
|
| No Change |
|
| 1 Point Worsening |
|
| 2 Point Worsening |
|
| 3 Point Worsening |
|
| 4 Point Worsening |
|