COVID-19, SARS-CoV 2
Conditions
Keywords
Coronavirus, COVID, Convalescent Plasma
Brief summary
This is a double-blinded, randomized control trial to assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma as early treatment. Participants will be randomized 2:1 to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody (anti-SARS-CoV-2 plasma) or control (albumin 5%). This study will investigate the potential of convalescent plasma (CP) to reduce severity of and/or help treat SARS-CoV-2 disease in patients with mild disease.
Detailed description
There are no approved therapies for Coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposure to viruses results in an adaptive immune response that commonly include antibodies with neutralization activity. Plasma from subjects who have recovered from viral infections has been used to both prevent or treat disease. Notable examples of the successful use of convalescent plasma (CP) include influenza, measles, Argentine hemorrhagic fever, Middle East respiratory syndrome (MERS), Ebola and severe acute respiratory syndrome (SARS). In recent work in China, an open label safety trial of CP in patients with COVID-19 suggested a substantive benefit.
Interventions
BIOLOGICALControl (albumin 5%)
Albumin (Human) 5% is a sterile aqueous solution for intravenous use containing the albumin component human plasma.
Convalescent Plasma that contains antibody titers against SARS-CoV-2.
Sponsors
Andrew Eisenberger
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
A total of 150 eligible subjects will be randomized in a 2:1 ratio to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody (anti-SARS-CoV-2 plasma) or control (albumin 5%)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects must be 18 years of age or older * Recent close contact with a person with COVID-19, i.e. last close contact occurred within 7 days of anticipated infusion of study product. It is anticipated that most contacts will be household contacts with extensive interaction. All must meet the CDC criteria for close contacts. This includes healthcare workers at higher risk of developing severe disease. OR * Recent self-reported or documented evidence of infection by nasal swab PCR that is positive for SARS-CoV-2, i.e., nasal sample was collected within 7 days or 10 days of anticipated infusion of study product for those who are asymptomatic or symptomatic, respectively. * Evidence of infection by nasal swab PCR that is positive for SARS-CoV-2 at screening visit. * May or may not be hospitalized. * No symptoms or no more than 5 days of mild symptoms at the time of screening. Mild symptoms (rated by participant as mild and not interfering with normal daily activities) may include: * Mild rhinorrhea * Mild sore throat or throat irritation * Mild nonproductive cough * Mild fatigue (able to perform Activities of Daily Living (ADLs)) * Risk for severe COVID-19 based on a risk score of ≥ 1 Calculated Risk Score of ≥ 1 point, with risk factors based on Center for Disease Control and Prevention (CDC) description * Age 65-74: 1 point * Age ≥ 75: 2 points * Known cardiovascular disease (including hypertension): 1 point * Diabetes mellitus: 1 point * Pulmonary disease (COPD, moderate to severe asthma, current smoking or other): 1 point * Morbid obesity: 1 point * Immunocompromised state: 1 point Received a bone marrow or solid organ transplant at any time, received chemotherapy for a malignancy within the past 6 months, has an acquired or congenital immunodeficiency, currently receiving immunosuppressive or immune modulating medications, HIV with non-suppressed viral load and/or cluster of differentiation 4 (CD4+) T cell count \<200 cells/mL).
Exclusion criteria
* Receipt of any blood product in past 120 days. * Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance. * Confirmed or self-reported presumed COVID-19, with symptoms that began more than 5 days prior to enrollment, and SARS-CoV-2 PCR positive sample that was collected more than 7 days prior to anticipated infusion for an asymptomatic participant or more than 10 days prior to anticipated infusion for a patient with mild symptoms at screening. * Symptoms consistent with COVID---19 infection that are more than mild (as defined above) at time of screening. * Symptoms consistent with COVID---19 infection that are more than mild at time of screening. * History of allergic reaction to transfusion blood products * Inability to complete infusion of the product within 48 hours after randomization. * Resident of a long term or skilled nursing facility * Known prior diagnosis of immunoglobulin A (IgA) deficiency * Oxygen saturation that is \< 95% at the screening visit * On supplemental oxygen at time of enrollment * Participation in another clinical trial of anti-viral agent(s) for COVID-19 * Receipt of any COVID-19 vaccine, either as part of a clinical research trial or through routine service delivery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Non-Hospitalized Participants | Up to 28 days | Participants who were discharged from the hospital after receiving the study intervention. |
| Number of Hospitalized Participants Requiring Supplemental Oxygen | Up to 28 days | Participants who remained hospitalized and required supplemental oxygen after receiving the study drug. |
| Number of Hospitalized Participants Requiring High-flow Oxygen Therapy or Noninvasive Mechanical Ventilation | Up to 28 days | Participants who remained hospitalized and required high-flow oxygen therapy or noninvasive mechanical ventilation after receiving the study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of SARS-CoV-2 PCR Positivity | Up to 28 days | Compare the duration of SARS-CoV-2 PCR positivity (RT PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (albumin 5%). |
| Number of In-hospital Mortalities | Up to 28 days | Participants who died in the hospital after receiving the study drug. |
| Levels of SARS-CoV-2 RNA | Up to 28 days | Compare the levels of SARS-CoV-2 RNA between the recipients of antiSARS-CoV-2 plasma and control (albumin 5%) |
| Rate of Measurable Anti-SARS-CoV-2 Titers | Up to 90 days | To compare the rate of measurable anti-SARS-CoV-2 titers between recipients of CP (anti-SARS-CoV-2 plasma) versus control (albumin 5%). |
| Rate of SARS-CoV-2 PCR Positivity | Up to 28 days | Compare the rates of SARS-CoV-2 PCR positivity (RT PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (albumin 5%). |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Arm: Convalescent Plasma Participants will receive 2 units (approximately 200 to 250 mL per unit, total 400-500mL) of convalescent plasma that was collected from a volunteer who recovered from COVID-19 disease. | 150 |
| Control Arm: Albumin 5% Participants will receive 2 units of 250 mL (500mL total) of human albumin 5% infusion. Albumin 5% is a sterile aqueous solution for intravenous use containing the albumin component human plasma. The albumin will be prepared in bags that are identical to the bags used for plasma. The similar appearance of albumin and plasma will facilitate maintaining the blinded status of subjects and most of the study staff. | 73 |
| Total | 223 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Physician Decision | 2 | 1 |
Baseline characteristics
| Characteristic | Experimental Arm: Convalescent Plasma | Control Arm: Albumin 5% | Total |
|---|---|---|---|
| Age, Customized 60-69 years | 35 Participants | 24 Participants | 59 Participants |
| Age, Customized <60 years | 74 Participants | 28 Participants | 102 Participants |
| Age, Customized 70-79 years | 28 Participants | 16 Participants | 44 Participants |
| Age, Customized ≥80 years | 13 Participants | 5 Participants | 18 Participants |
| Baseline conditions Chronic cardiac disease | 56 Participants | 28 Participants | 84 Participants |
| Baseline conditions Chronic kidney disease | 13 Participants | 8 Participants | 21 Participants |
| Baseline conditions Chronic liver disease | 3 Participants | 1 Participants | 4 Participants |
| Baseline conditions Chronic pulmonary disease | 15 Participants | 5 Participants | 20 Participants |
| Baseline conditions COVID-19 | 150 Participants | 73 Participants | 223 Participants |
| Baseline conditions Diabetes mellitus | 55 Participants | 27 Participants | 82 Participants |
| Baseline conditions HIV | 4 Participants | 0 Participants | 4 Participants |
| Baseline conditions Hyperlipidemia | 27 Participants | 9 Participants | 36 Participants |
| Baseline conditions Hypertension | 53 Participants | 22 Participants | 75 Participants |
| Clinical status at randomization Hospitalized, not requiring supplemental oxygen | 5 Participants | 5 Participants | 10 Participants |
| Clinical status at randomization Hospitalized, requiring IMV, ECMO, or both | 17 Participants | 11 Participants | 28 Participants |
| Clinical status at randomization Hospitalized, requiring supplemental oxygen, HFO, NIV | 125 Participants | 57 Participants | 182 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Brazil | 101 participants | 49 participants | 150 participants |
| Region of Enrollment United States | 49 participants | 24 participants | 73 participants |
| Sex: Female, Male Female | 96 Participants | 51 Participants | 147 Participants |
| Sex: Female, Male Male | 54 Participants | 22 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 150 | 18 / 73 |
| other Total, other adverse events | 38 / 147 | 17 / 72 |
| serious Total, serious adverse events | 39 / 147 | 26 / 72 |
Outcome results
Primary
Number of Hospitalized Participants Requiring High-flow Oxygen Therapy or Noninvasive Mechanical Ventilation
Participants who remained hospitalized and required high-flow oxygen therapy or noninvasive mechanical ventilation after receiving the study intervention.
Time frame: Up to 28 days
Population: Only includes individuals who have data at day 28.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: Convalescent Plasma | Number of Hospitalized Participants Requiring High-flow Oxygen Therapy or Noninvasive Mechanical Ventilation | 1 Participants |
| Control Arm: Albumin 5% | Number of Hospitalized Participants Requiring High-flow Oxygen Therapy or Noninvasive Mechanical Ventilation | 0 Participants |
Primary
Number of Hospitalized Participants Requiring Supplemental Oxygen
Participants who remained hospitalized and required supplemental oxygen after receiving the study drug.
Time frame: Up to 28 days
Population: Only includes individuals who have data at day 28.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: Convalescent Plasma | Number of Hospitalized Participants Requiring Supplemental Oxygen | 7 Participants |
| Control Arm: Albumin 5% | Number of Hospitalized Participants Requiring Supplemental Oxygen | 1 Participants |
Primary
Number of Non-Hospitalized Participants
Participants who were discharged from the hospital after receiving the study intervention.
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: Convalescent Plasma | Number of Non-Hospitalized Participants | 108 Participants |
| Control Arm: Albumin 5% | Number of Non-Hospitalized Participants | 48 Participants |
Secondary
Duration of SARS-CoV-2 PCR Positivity
Compare the duration of SARS-CoV-2 PCR positivity (RT PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (albumin 5%).
Time frame: Up to 28 days
Population: Data was not collected for this outcome measure.
Secondary
Levels of SARS-CoV-2 RNA
Compare the levels of SARS-CoV-2 RNA between the recipients of antiSARS-CoV-2 plasma and control (albumin 5%)
Time frame: Up to 28 days
Population: Samples were not collected for analysis.
Secondary
Number of In-hospital Mortalities
Participants who died in the hospital after receiving the study drug.
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: Convalescent Plasma | Number of In-hospital Mortalities | 19 Participants |
| Control Arm: Albumin 5% | Number of In-hospital Mortalities | 18 Participants |
Secondary
Rate of Measurable Anti-SARS-CoV-2 Titers
To compare the rate of measurable anti-SARS-CoV-2 titers between recipients of CP (anti-SARS-CoV-2 plasma) versus control (albumin 5%).
Time frame: Up to 90 days
Population: These samples were not collected for analysis.
Secondary
Rate of SARS-CoV-2 PCR Positivity
Compare the rates of SARS-CoV-2 PCR positivity (RT PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (albumin 5%).
Time frame: Up to 28 days
Population: These samples were not collected for analysis.