Coronavirus, Coronavirus Infection, COVID-19
Conditions
Brief summary
This is a randomized, blinded phase 2 trial that will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms requiring oxygen supplementation.
Detailed description
A total of 300 eligible subjects will be randomized in a 1:1 ratio to receive either convalescent plasma (CP) from people who have recovered from COVID-19 containing antibodies to SARS-CoV-2 or a placebo control, Lactated Ringer's Solution (LR) or saline solution (SS). Hospitalized COVID-19 patients aged ≥18 years of age with respiratory symptoms within 3 to 7 days from the onset of illness OR within 3 days of hospitalization will be eligible to participate.
Interventions
BIOLOGICALConvalescent Plasma
SARS-CoV-2 convalescent plasma (1-2 units; \ 250-500 mL) with antibodies to SARS-CoV-21 per April 13, 2020 directive by the FDA, obtained from New York Blood Center will be administered to eligible candidate
OTHERSaline solution
Equivalent volume of saline solution (defined as half-,quarter-, or normal saline) will be administered to eligible candidate as a placebo control group.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
Albert Einstein College of Medicine
Yale University
The University of Texas Health Science Center, Houston
The University of Texas Health Science Center at Tyler
University of Miami
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥18 years of age 2. Hospitalized with laboratory confirmed COVID-19 3. One or more of the following respiratory signs or symptoms: cough, chest pain, shortness of breath, fever, oxygen saturation ≤ 94%, abnormal CXR/CT imaging) 4. Hospitalized for ≤ 72 hours OR within day 3 to 7 days from first signs of illness 5. On supplemental oxygen, non-invasive ventilation or high-flow oxygen 6. Patients may be on other randomized controlled trials of pharmaceuticals for COVID -19 and patients who meet eligibility criteria will not be excluded on this basis.
Exclusion criteria
1. Receipt of pooled immunoglobulin in past 30 days 2. Contraindication to transfusion or history of prior reactions to transfusion blood products 3. Invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 4. Volume overload secondary to congestive heart failure or renal failure 5. Unlikely to survive past 72 hours from screening based on the assessment of the investigator 6. Unlikely to be able to assess and follow outcome due to poor functional status
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 14 Days | 14 days post-randomization | Uninfected 0 Uninfected; no viral RNA detected Ambulatory 1 Asymptomatic; viral RNA detected 2 Symptomatic; Independent 3 Symptomatic; assistance needed Hospitalized: Mild disease 4 Hospitalized; no oxygen therapy 5 Hospitalized; oxygen by mask or nasal prongs Hospitalized: Severe disease 6 Hospitalized; oxygen by NIV or High flow 7 Intubation & Mechanical ventilation; pO2/FIO2 \>/= 150 or SpO2/FIO2 \>/=200 8 Mechanical ventilation pO2/FIO2 \< 150 (SpO2/FIO2 \<200) or vasopressors 9 Mechanical ventilation pO2/FIO2 \< 150 and vasopressors, dialysis or ECMO Death 10 Dead |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 28 Days | 28 days post-randomization | Uninfected 0 Uninfected; no viral RNA detected Ambulatory 1 Asymptomatic; viral RNA detected 2 Symptomatic; Independent 3 Symptomatic; assistance needed Hospitalized: Mild disease 4 Hospitalized; no oxygen therapy 5 Hospitalized; oxygen by mask or nasal prongs Hospitalized: Severe disease 6 Hospitalized; oxygen by NIV or High flow 7 Intubation & Mechanical ventilation; pO2/FIO2 \>/= 150 or SpO2/FIO2 \>/=200 8 Mechanical ventilation pO2/FIO2 \< 150 (SpO2/FIO2 \<200) or vasopressors 9 Mechanical ventilation pO2/FIO2 \< 150 and vasopressors, dialysis or ECMO Death 10 Dead |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Convalescent Donor Plasma Convalescent Plasma: SARS-CoV-2 convalescent plasma (1-2 units; \
250-500 mL) with antibodies to SARS-CoV-21 per April 13, 2020 directive by the FDA, obtained from New York Blood Center will be administered to eligible candidate | 463 |
| Lactated Ringer's Solution or Sterile Saline Solution Saline solution: Equivalent volume of saline solution (defined as half-,quarter-, or normal saline) will be administered to eligible candidate as a placebo control group. | 463 |
| Total | 926 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 9 |
Baseline characteristics
| Characteristic | Convalescent Donor Plasma | Total | Lactated Ringer's Solution or Sterile Saline Solution |
|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 15.2 | 62.35 years STANDARD_DEVIATION 15.15 | 63.3 years STANDARD_DEVIATION 15.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 181 Participants | 367 Participants | 186 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 282 Participants | 559 Participants | 277 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 41 Participants | 71 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 71 Participants | 139 Participants | 68 Participants |
| Race (NIH/OMB) More than one race | 76 Participants | 146 Participants | 70 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 36 Participants | 17 Participants |
| Race (NIH/OMB) White | 256 Participants | 534 Participants | 278 Participants |
| Region of Enrollment United States | 463 participants | 926 participants | 463 participants |
| Sex: Female, Male Female | 184 Participants | 381 Participants | 197 Participants |
| Sex: Female, Male Male | 279 Participants | 545 Participants | 266 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 468 | 3 / 473 |
| other Total, other adverse events | 147 / 468 | 136 / 473 |
| serious Total, serious adverse events | 112 / 468 | 108 / 473 |
Outcome results
Primary
Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 14 Days
Uninfected 0 Uninfected; no viral RNA detected Ambulatory 1 Asymptomatic; viral RNA detected 2 Symptomatic; Independent 3 Symptomatic; assistance needed Hospitalized: Mild disease 4 Hospitalized; no oxygen therapy 5 Hospitalized; oxygen by mask or nasal prongs Hospitalized: Severe disease 6 Hospitalized; oxygen by NIV or High flow 7 Intubation & Mechanical ventilation; pO2/FIO2 \>/= 150 or SpO2/FIO2 \>/=200 8 Mechanical ventilation pO2/FIO2 \< 150 (SpO2/FIO2 \<200) or vasopressors 9 Mechanical ventilation pO2/FIO2 \< 150 and vasopressors, dialysis or ECMO Death 10 Dead
Time frame: 14 days post-randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Convalescent Donor Plasma | Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 14 Days | 2 score on a scale |
| Lactated Ringer's Solution or Sterile Saline Solution | Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 14 Days | 2 score on a scale |
Secondary
Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 28 Days
Uninfected 0 Uninfected; no viral RNA detected Ambulatory 1 Asymptomatic; viral RNA detected 2 Symptomatic; Independent 3 Symptomatic; assistance needed Hospitalized: Mild disease 4 Hospitalized; no oxygen therapy 5 Hospitalized; oxygen by mask or nasal prongs Hospitalized: Severe disease 6 Hospitalized; oxygen by NIV or High flow 7 Intubation & Mechanical ventilation; pO2/FIO2 \>/= 150 or SpO2/FIO2 \>/=200 8 Mechanical ventilation pO2/FIO2 \< 150 (SpO2/FIO2 \<200) or vasopressors 9 Mechanical ventilation pO2/FIO2 \< 150 and vasopressors, dialysis or ECMO Death 10 Dead
Time frame: 28 days post-randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Convalescent Donor Plasma | Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 28 Days | 2 score on a scale |
| Lactated Ringer's Solution or Sterile Saline Solution | Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 28 Days | 2 score on a scale |