Convalescent Plasma as Adjunctive Therapy for Hospitalized Patients With COVID-19

This is a phase 3, randomized, non-placebo controlled, open-label, single-center clinical trial which will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma given from the 3rd to 14th day of illness after the onset of symptoms in preventing ICU admission among hospitalized COVID-19 patients compared to standard of care. Consecutive patients with COVID-19 admitted to the UP Philippine General Hospital will be offered participation into the study. Patients in the intervention group will receive one dose of type-specific anti-SARS-CoV-2 convalescent plasma (500 mL collected by whole blood donation or standard pheresis at the UP-PGH blood bank from a volunteer who recovered from COVID-19). The primary safety endpoints include serious adverse events judged to be related to convalescent plasma. The study also aims to compare anti-SARS-CoV-2 antibody titers and rates, levels, and duration of SARS-CoV-2 RNA in nasopharyngeal swabs using RT-PCR between the intervention and control groups.

• Anti-SARS-CoV-2 convalescent plasma (Drug): convalescent plasma derived from whole blood donors or standard pheresis from a volunteer who recovered from COVID-19

Primary outcomes

• Incidence of serious adverse events [28 days from enrollment]: Cumulative incidence of serious adverse events (transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion related infection and anaphylaxis/severe allergic reactions) during the study period

Secondary outcomes

• Quick SOFA (qSOFA) score [28 days from enrollment]: Quick Sequential Organ Failure Assessment (qSOFA) scores of study participants within 28 days from enrollment. The qSOFA score is a rapid bedside clinical score used to identify patients with suspected infection that are at a greater risk for a poor outcome. Minimum score is 0 and maximum score is 3. A higher score is associated with higher risk for in-hospital mortality.
• Cardiopulmonary arrest [28 days from enrollment]: Total number of patients experiencing cardiopulmonary arrest
• ICU mortality [28 days from enrollment]: Total number of deaths among patients admitted to the ICU
• ICU length of stay [28 days from enrollment]: Total number of days patients were admitted to the ICU
• Hospital mortality [28 days from enrollment]: Total number of deaths among study participants
• Hospital length of stay [28 days from enrollment]: Total number of days patients were admitted to the hospital
• Dialysis-free days [28 days from enrollment]: Days without dialysis within 28 days from enrollment
• Vasopressor-free days [28 days from enrollment]: Days without vasopressors within 28 days from enrollment
• ICU-free days [28 days from enrollment]: Days without need for ICU admission within 28 days from enrollment
• 28-day mortality [28 days from enrollment]: Total number of patient deaths within 28 days from enrollment
• Anti-SARS-CoV-2 antibody titers [days 0, 1, 7 and 14 of enrollment]: Anti-SARS-CoV-2 IgG antibody titers
• SARS-CoV-2 RNA by RT-PCR [days 0, 1, 7 and 14 of enrollment]: Levels of SARS-CoV-2 RNA in nasopharyngeal swabs (or other specimen types as available) using RT-PCR

Sex: All, ages: 19 Years to any

Inclusion Criteria:

* Patient must be 19 years of age or older
* Hospitalized with COVID-19 and confirmed via SARS-CoV-2 RT-PCR testing
* Patient is willing and able to provide written consent and comply with all protocol requirements
* Patient agrees to storage of specimens for future testing

Exclusion Criteria:

* Female subjects with positive pregnancy test, are breastfeeding or planning to become pregnant/breastfeed during the study period
* Symptomatic illness exceeding 14 days from onset of illness at time of enrollment
* ICU admission on initial presentation at the hospital (includes patients with clinical indications for ICU admission as follows:

  1. Respiratory distress with requirement of O2 >6 lpm to maintain O2 sat >92%
  2. Rapid escalation of O2 requirement/significant work of breathing
  3. Hemodynamic instability: SBP <90, MAP <65
* Receipt of any blood products including pooled immunoglobulin or intravenous immunoglobulin (IVIg) in the past 30 days prior to enrolment
* Known IgA deficiency
* Presence of any contraindication to transfusion (or history of prior severe reactions to transfusion of blood products)

• Deonne Thaddeus V Gauiran, MD, Principal investigator, UP Philippine General Hospital