Early Use of Hyperimmune Plasma in COVID-19

Study Overview
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Brief Summary
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The study assesses the efficacy of early administration of hyperimmune plasma in covid-19 patients who are on CPAP or intubated. Efficacy is measured as a 2 point decrease in the WHO scale

Detailed Description
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Patients who satisfy eligibility criteria and in particular have started positive pressure respiratory support not more than no more than 48 hours are administered 200 to 300 ml in 2 or 3 times administered over a time window of 5 days. . Plasma titration will depend on the availability in the local Plasma Bank; any titre ≥ 1:80 will be acceptable. primary endpoint will be assessed at 28 days; vital status will be further investigated at 3 and 6 months.

Official Title
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COVID-19 Wave II Study for Assessing the Early Use of Hyperimmune Plasma for the Treatment of COVID-19 Patients Needing Non-invasive or Invasive Mechanical Ventilation

Conditions
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Covid19

Intervention / Treatment
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* Other: hyperimmune plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to performing study procedures. Witnessed oral consent will be accepted in order to avoid paper handling. Written consent by patient or representatives will be obtained as soon as possible. Male or female adult patient ≥18 years of age at time of enrolment. Laboratory-confirmed SARS-CoV-2 infection as determined by real-time RT-PCR in naso/oropharyngeal swabs or any other relevant specimen.. Patient is hospitalized for COVID-19, is severely hypoxic with a P/F ≤ 200 while breathing room air or supplemental oxygen and requires positive pressure respiratory support, either non-invasive (helmet/mask CPAP or NIV) or invasive (endotracheal intubation and mechanical ventilation) No more than 48 hours between the onset of positive pressure respiratory support and treatment administration day Evidence of pulmonary infiltrates at chest imaging (chest x-ray, CT scan or LUS) The patient is not eligible in the Tsunami trial. Exclusion Criteria: Participation in any other clinical trial of an experimental treatment for COVID-19. In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30). Pregnancy Current documented and uncontrolled bacterial infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: a multiple center, one arm clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single<br>hyperimmune plasma with titre 1:80 or more | Other: hyperimmune plasma<br>* plasma collected from convalescent Covid-19 donors with titre 1:80 or more<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement (efficacy) | Clinical improvement is obtained when a patient decreases his/her score by 2 points on the ten-category ordinal WHO scale or is discharged alive from the hospital, whichever comes first. The WHO scale is chosen in accordance with the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme recently published in Lancet Infectious Diseases (WHO, 2020). | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ventilation | Ventilator-free days | Days: from 0 to 7, 14 and 28 | 
| WHO (World Health Organization) scale | WHO scale score reached. Minimum score is 0: unifected (no viral RNA detected); maximum score 10 (dead) | From day 0 to 28 days | 
| SOFA (Sequential Organ Failure Assessment) score | Sequential Organ Failure Assessment Score (SOFA score). This score is used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing with higher the scores | Days: from 0 to 7, 14 and 28 | 
| naso-pharyngeal swab | Time to a negative SARS-COV2 naso-pharyngeal swab for upper respiratory tract or BAL/BRASP for lower respiratory | Days: from 0 to 7, 14 and 28 | 
| SARS-CoV2 | Log10 change in SARS-CoV2 | 28 days | 
| P/F | P/F ratio. P/F is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage) | Days: from 0 to 7, 14 and 28 | 
| thrombosis | Occurrence of deep vein thrombosis or pulmonary embolism assessed using the most appropriate imaging approach | Days: from 0 to 7, 14 and 28 | 
| curarization | Total duration of mechanical ventilation, ventilatory weaning and curarisation in days | Days: from 0 to 7, 14 and 28 | 
| complication kidney | KDIGO score Kidney Disease: Improving Global Outcomes (KDIGO) | Days: from 0 to 7, 14 and 28 | 
| complication lung | Occurrence of ventilator-acquired pneumonia - Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling | Days: from 0 to 7, 14 and 28 | 
| Leucocytes | Biological efficacy endpoints: Leucocytes (x10^3/ul) | Days: from 0 to 7, 14 and 28 | 
| Lymphocytes | Biological efficacy endpoints: Lymphocytes (x10^3/ul) | Days: from 0 to 7, 14 and 28 | 
| C-reactive protein | Biological efficacy endpoints: C-reactive protein (mg/dL) | Days: from 0 to 7, 14 and 28 | 
| D-dimer | Biological efficacy endpoints: D-dimer (ug/L) | Days: from 0 to 7, 14 and 28 | 
| Troponin I (TnI) | Biological efficacy endpoints: TNI (ng/L) | Days: from 0 to 7, 14 and 28 | 
| PCTI (Procalcitonin) (ng/mL) | Biological efficacy endpoints: PCTI (Procalcitonin) (ng/mL) | Days: from 0 to 7, 14 and 28 | 
| Ferritin | Biological efficacy endpoints: Ferritin (ng/ml) | Days: from 0 to 7, 14 and 28 | 
| Albumin | Biological efficacy endpoints: Albumin (mg/dL) | Days: from 0 to 7, 14 and 28 | 
| LDH | Biological efficacy endpoints: LDH (mU/mL) | Days: from 0 to 7, 14 and 28 | 
| Lung Ultrasound Score (LUS) | Total Lung Ultrasound Score S score | Days: from 0 to 7, 14 , 28 and 6 months | 
| ecmo | Occurrence of ECMO implant | 28 days | 
| death | All cause mortality | 28 days, 3 and 6 months | 
| hospitalization | days total hospitalization and of ICU hospitalization | 28 days | 
| Lung Function tests | Lung Function tests | 6 months | 
| High resolution computed tomography (HRCT) | HRCT findings of the thorax | 6 months | 
| Improvement mortality | rate of clinical improvement and mortality between the patients in the study and the cohort enrolled in the local SMACORE registry | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperimmune plasma, positive pressure respiratory support