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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
75
Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection.
0.9% saline solution will be used as the Masked Saline Placebo
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.
Time frame: Day 1 through Day 28
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.
Time frame: 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.
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
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.
Time frame: 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.
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Birmingham VA Medical Center, Birmingham, AL
Birmingham, Alabama, United States
Phoenix VA Health Care System, Phoenix, AZ
Phoenix, Arizona, United States
Rocky Mountain Regional VA Medical Center, Aurora, CO
Aurora, Colorado, United States
North Florida/South Georgia Veterans Health System, Gainesville, FL
Gainesville, Florida, United States
Orlando VA Medical Center, Orlando, FL
Orlando, Florida, United States
James A. Haley Veterans' Hospital, Tampa, FL
Tampa, Florida, United States
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, United States
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, United States
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, United States
John D. Dingell VA Medical Center, Detroit, MI
Detroit, Michigan, United States
...and 14 more locations
Time frame: Day 1 through Day 28
Number of Participants With 28-day All-cause Mortality
Death for Any Reason
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
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
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.
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
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.
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
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.
Time frame: From Day 1 (baseline) to Days 2, 4, 7, 11, 15, and 29
Duration of Hospitalization
Number of Days Hospitalized During Initial Hospitalization
Time frame: 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
Time frame: Day 1 through Day 3