Effects of COVID-19 Convalescent Plasma (CCP) on Coronavirus-associated Complications in Hospitalized Patients

A total of 50 eligible subjects will be randomized in a 1:1 ratio to receive either convalescent fresh frozen plasma (frozen within 8 hours of collection) of PF24 (frozen within 24 hours) from blood donors who have recovered from COVID-19 containing antibodies to SARS-CoV-2 or control (standard fresh frozen plasma collected prior to 12/1/2019 or with documented negative SARS-CoV-2 antibody). Should additional anti-COVID agents (anti-viral and/or anti-inflammatory) become available for use as standard of care during implementation, the sample size will be recalculated and increased to account for the estimated impact that these agents may have on the reducing the progression to the primary endpoint of severe hypoxemia.

• COVID-19 Convalescent Plasma (CCP) (Biological): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.
• Placebo (Biological): Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.

Primary outcomes

• Mechanical Ventilation or Death Endpoint [Day 14]: Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment.

Secondary outcomes

• Mechanical Ventilation or Death Endpoint [Day 28]: Progression to mechanical ventilation or death within the first 28 days of enrollment.
• 8-Point Ordinal Scale Endpoint [Day 29]: Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. 8 Point WHO Ordinal Scale of Clinical Status: Uninfected (No clinical or virological evidence of infection) - 0 Ambulatory (No limitation of activities) - 1 Ambulatory (Limitation of Activities) - 2 Hospitalized Mild Disease (Hospitalized, no oxygen therapy) - 3 Hospitalized Mild Disease (Oxygen by mask or nasal prongs) - 4 Hospitalized Severe Disease (Non-invasive ventilation or high flow oxygen) - 5 Hospitalized Severe Disease (Intubation and mechanical ventilation) - 6 Hospitalized Severe Disease (Ventilation + Additional organ support (pressors, RRT, ECMO)) - 7 Dead (Death) - 8

Sex: All, ages: 18 Years to any

Inclusion Criteria for Enrollment:

1. Patients ≥18 years of age
2. Hospitalized with COVID-19
3. Enrolled within 72 hours of hospitalization OR within day 14 from first signs of illness
4. Pulmonary infiltrates on chest imaging
5. Oxygenation of <95% on room air
6. Laboratory confirmed COVID-19

Exclusion Criteria

1. Contraindication to transfusion due to inability to tolerate additional fluid, such as due to decompensated congestive heart failure
2. Baseline requirement for oxygen supplementation prior to COVID-19 infection or use of positive pressure therapy for sleep disordered breathing
3. Currently experiencing severe hypoxemic failure, as defined in study endpoints
4. Prior receipt of plasma products, IVIG, or hyperimmune globulin within past 3 months
5. Not currently enrolled another interventional clinical trial of COVID-19 treatment.

Note: If taking medications with potential anti-COVID activity for the purpose of COVID-19 treatment that do not yet have data to support efficacy, such as IL-6 antagonists, these medications must be stopped prior to enrollment. Receipt of current standard of care COVID-19 treatment, including remdesivir and dexamethasone is permitted and should be recorded as a concomitant medication.

Note: Pregnancy is not exclusionary but will merit additional discussion of risks \& benefits in the context of ongoing pregnancy

Participant flow

Outcome results

• Mechanical Ventilation or Death Endpoint (Primary), Count of participants, Participants: COVID-19 Convalescent Plasma 2; Placebo 0
• Mechanical Ventilation or Death Endpoint (Secondary), Count of participants, Participants: COVID-19 Convalescent Plasma 2; Placebo 0
• 8-Point Ordinal Scale Endpoint (Secondary), Mean, score on a scale: COVID-19 Convalescent Plasma 2.43 (1 to 4); Placebo 1.93 (1 to 3)

Adverse events

Time frame: 90 days

Serious adverse events by term

Other adverse events by term

Limitations and caveats: This study was limited by the small sample of hospitalized, hypoxic patients, limiting the generalizability of the results. Most participants were beyond 72 hours of symptom onset, the period when studies suggest CCP is most likely to be beneficial.

• Study Protocol and Statistical Analysis Plan (PDF, 2020-07-26)
• Informed Consent Form (PDF, 2020-07-29)

• Priscilla Hsue, MD, Principal investigator, University of California, San Francisco
• Annie Leutkemeyer, MD, Principal investigator, University of California, San Francisco