NCT04353206.

Study name	A feasibility study assessing the safety of multiple doses of anti‐SARS‐CoV‐2 plasma in mechanically ventilated intubated patients with respiratory failure due to COVID‐19
Methods	Trial design: single‐arm, interventional Sample size: 90 Setting: ICU Country: USA Language: English  Number of centres: 3
Participants	Inclusion criteria ≥ 18 years Respiratory failure requiring mechanical ventilation due to COVID‐19‐induced pneumonia with confirmation via SARS‐CoV‐2 RT‐PCR testing PaO2/FiO2 ratio < 300 (or SpO2/FiO2 < 315) Bilateral pulmonary infiltrates Exclusion criteria Contraindication to transfusion (severe volume overload, history of anaphylaxis to blood products) In the opinion of the site investigator or primary clinical care team, anticipated to die within 48 h Acute or chronic disease/illness that, in the opinion of the site investigator, has an expected life expectancy of < 28 days unrelated to COVID‐19‐induced pneumonia (e.g. stage IV malignancy, neurodegenerative disease, anoxic brain injury, etc.) Use of home oxygen at baseline Use of home mechanical ventilation at baseline (CPAP or bi‐level positive airway pressure without need for oxygen is NOT an exclusion) Respiratory failure caused by illness other than SARS‐CoV‐2 Other documented uncontrolled infection > 72 h have elapsed since first meeting inclusion criteria Severe disseminated intravascular coagulation, TTP, or antithrombin III deficiency needing factor replacement, fresh‐frozen plasma, cryoprecipitate On warfarin and deemed necessary to maintain therapeutic international normalised ratio (because the CP will reverse the warfarin effect) On dialysis at the time enrolment is considered Active intracranial bleeding Clinically significant myocardial ischaemia Prisoner or incarceration Pregnancy or active breast feeding Has already received CP for COVID‐19 infection during current admission Current participation in another interventional research study Inability or unwillingness of subject or legal surrogate/representative to give written informed consent
Interventions	CP therapy or hyperimmune globulin therapy: CP therapy Details of CP: type of plasma: as per FDA guidelines  volume: NR number of doses: 1‐6 (1‐2 units day 0, 3, 6) antibody‐titre: NR pathogen inactivated or not: NR Treatment details, including time of plasma therapy (e.g. early stage of disease): not > 72 h have elapsed since first meeting inclusion criteria For studies including a control group: comparator (type): none Concomitant therapy: NR Treatment cross‐overs: none
Outcomes	Primary study outcome: proportion of participants who consent to the study and receive at least one dose of CP Primary review outcomes All‐cause mortality at hospital discharge: yes (up to 60 days) Time to death: yes (up to 60 days) Secondary review outcomes Number of participants with grade 3 and grade 4 AEs, including potential relationship between intervention and adverse reaction (e.g. TRALI, transfusion‐transmitted infection, TACO, TAD, acute transfusion reactions): NR Number of participants with SAEs: NR Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: yes 30‐day and 90‐day mortality: yes (up to 60 days) Admission on the ICU: yes (all in ICU) Length of stay on the ICU: NR Time to discharge from hospital: NR QoL: NR Additional outcomes Proportion of participants who consent to the study and receive at least one dose of CP (time frame: 60 days) Respiratory status and overall clinical status will be reviewed during follow up (on days 14, 28, and 60)
Starting date	May 2020
Contact information	Noah Merin, MD PhD; 310‐423‐1160; Noah.Merin@cshs.org David Hager, MD PhD; dhager1@jhmi.edu
Notes	Recruitment status: not yet recruiting  Prospective completion date: May 2021 Sponsor/funding: Noah Merin, Johns Hopkins University, University of Pittsburgh Medical Center