NL8633.

Study name	A randomized, double blinded clinical trial of convalescent plasma compared to standard plasma for treatment of hospitalized non‐ICU patients with COVID‐19 infections (COV‐PLAS)
Methods	Trial design: randomised, prospective, multi‐centre, double‐blinded phase 2/3 trial Sample size: 215 each arm (430) Setting: inpatient Country: The Netherlands Language: English Number of centres: multi‐centre     Trial registration number: prospective ‐ NL8633  Date of registration: 13 May 2020
Participants	Inclusion criteria Maximal 3 days hospitalised at plasma infusion Age ≥ 18 years and ≤ 85 years SARS‐CoV‐2 infection: confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap) < 7 days before Symptoms not expected to lead to IC transfer within 6 h of study plasma administration Written informed consent including storing of specimen for future testing Exclusion criteria A potential participant who meets any of the following criteria will be excluded from participation in this study: Accompanying diseases other than COVID‐19 with an expected survival time of < 6 months Chronic severe pulmonary dysfunction like COPD, GOLD stage 4; severe emphysema; or lung fibrosis with usual interstitial pneumonia pattern Chronic heart failure NYHA ≥ 3 and/or pre‐existing reduction of left ventricular ejection fraction to ≤ 30% for which among others e.g. strict fluid restriction is needed Clinical diagnosis of circulatory overload for which active therapy (like increased doses of diuretics) is initiated Clinical judgement of deterioration in oxygenation (e.g. > 2 L increase in additional O2 by nose tube), respiratory rates (e.g. > 5 / min increase) in the 2 h before the planned randomisation/plasma infusion Signs of severe coagulopathy: thrombocytopenia by consumption (< 100 x 10e9/L) or prolongation of the PT (+3 sec) , PTT (+ 5 sec) Any history of severe adverse reactions to plasma proteins Known deficiency of IgA Pregnancy Breastfeeding women Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance
Interventions	Intervention(s):  CP therapy  vs standard plasma Details of CP: Type of plasma: convalescent thawed FFP Volume: 1 unit (250‐325 mL) Number of doses: 1 unit Antibody‐titre: NR Pathogen inactivated: NR Treatment details, including time of plasma therapy: Early. Maximally 3 days hospitalised COVID‐19 patients that are not at or bound to be referred to the ICU or expected to go to the ICU within 6 h of first plasma administration. Patients with COVID‐19 that are sick enough to warrant hospitalisation but have not (yet) experienced overwhelming disease including a systemic inflammatory response, sepsis, and/or ARDS warranting ventilation and (eminent) ICU referral Comparator: standard thawed FFP 1 unit (250‐325 mL) Concomitant therapy: NR Treatment cross‐overs: no ‐ parallel
Outcomes	Primary study outcome(s): Ordinal outcome at day 14 of all cause mortality, mechanical ventilation, ICU admission and long duration of hospital stay (6 days or more), with < 6 hospitalised days as reference category Primary review outcomes reported All‐cause mortality at hospital discharge: ordinal outcome of all‐cause mortality at day 6, 14, 21, 18 and 56 Length of ICU mortality Time to death: ordinal outcome of all‐cause mortality at day 14, 21, 18 and 56 ICU mortality Secondary review outcomes reported Number of participants with grade 3 and grade 4 adverse events, including potential relationship between intervention and adverse reaction: yes. Deterioration of respiratory, circulatory or otherwise the clinical status during transfusion; transfusion transmitted infections Number of participants with SAEs: numbers not mentioned: "The following safety parameters will be assessed during this trial: deterioration of respiratory, circulatory or otherwise the clinical status during transfusion; transfusion transmitted infections." Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: maybe. Ordinal outcome includes mechanical ventilation, ICU admission and long duration of hospital stay day 6, 14,  21, 28 30‐day and 90‐day mortality: yes. Ordinal outcome of all‐cause mortality, mechanical ventilation, ICU admission and long duration of hospital stay day 21, 28 and 56 Admission on ICU: yes within ordinal outcome of all‐cause mortality, mechanical ventilation, ICU admission and long duration of hospital stay day 6, 14, 21, 28 and 56 Length of stay on the ICU: Yes.  "Length of stay in ICU." Time to discharge from hospital: yes. "duration of hospitalisation in days" Additional outcomes e.g. proportion of viral nucleic acid negatives (3 days after transfusion): yes. "The time until negative SARS‐CoV‐2 PCR (nasal/ pharyngeal swab)" e.g. results of lab tests and vital signs: NR
Starting date	13 May 2020
Contact information	Name:  Jaap Jan Zwaginga Email:  j.j.zwaginga@lumc.nl Phone:  0715264006
Notes	Recruitment status: open for patient inclusion Prospective completion date: 1 May 2021 Sponsor: Leiden University Medical Center www.trialregister.nl/trial/8633