Convalescent Plasma in ICU Patients With COVID-19-induced Respiratory Failure

Study Overview
=================
Brief Summary
-----------------
This study will assess the feasibility of administering multiple doses of convalescent plasma (from people who have recovered form SARS-CoV-2) to Covid-19 positive patients in the Intensive Care Unit receiving mechanical ventilation. Donor plasma will not be obtained under this protocol, but all plasma used will follow FDA guidelines for Investigational COVID-19 Convalescent Plasma use. Patients may receive single or double plasma units infused on days 0, 3, and 6. This decision may be based on availability of blood plasma. The primary objective of this study is feasibility. Feasibility will be assessed based on the proportion of subjects who consent and receive at least one dose of convalescent plasma. The study will be declared 'feasible' if at least 80% of subjects who consent receive at least one dose. The secondary study endpoint is overall survival at day 60 after first dose of convalescent plasma. Respiratory status and overall clinical status will be reviewed during follow up on days 14, 28, and 60.

Detailed Description
-----------------
Convalescent plasma is an antibody-rich product made from blood donated by people who have recovered from the disease caused by the virus. Prior experience with respiratory viruses and limited data that have emerged from China suggest that convalescent plasma has the potential to lessen the severity or shorten the length of illness caused by COVID-19. It is important that we evaluate this potential therapy in the context of clinical trials. As such, this study will assess the feasibility of administering multiple doses of convalescent plasma (from people who have recovered form SARS-CoV-2) to Covid-19 positive patients in the Intensive Care Unit receiving mechanical ventilation. Donor plasma will not be obtained under this protocol, but all plasma used will follow FDA guidelines for Investigational COVID-19 Convalescent Plasma use. This study will be opened across three separate site: Cedars-Sinai Medical Center, Johns Hopkins University, and University of Pittsburgh Medical Center. 30 patients will be recruited at each site. Each site has received its own FDA IND and IRB approval. As such, the following people are serving as sponsor-investigators at their respective institutions. David Hager, MD PhD, Johns Hopkins University Noah Merin, MD PhD, Cedars-Sinai Medical Center Patients may receive single or double plasma units infused on days 0, 3, and 6. This decision may be based on availability of blood plasma. The primary objective of this study is feasibility. Feasibility will be assessed based on the proportion of subjects who consent and receive at least one dose of convalescent plasma. The study will be declared 'feasible' if at least 80% of subjects who consent receive at least one dose. The secondary study endpoint is overall survival at day 60 after first dose of convalescent plasma. Respiratory status and overall clinical status will be reviewed during follow up on days 14, 28, and 60.

Official Title
-----------------
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

Conditions
-----------------
Covid-19, Sars-CoV2

Intervention / Treatment
-----------------
* Biological: Multiple Doses of Anti-SARS-CoV-2 convalescent plasma


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older 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 hours. Acute or chronic disease/illness that, in the opinion of the site investigator, has an expected life expectancy of less than 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 BIPAP without need for oxygen is NOT an exclusion) Respiratory failure caused by illness other than SARS-CoV-2 Other documented uncontrolled infection. More than 72 hours have elapsed since first meeting inclusion criteria Severe DIC, TTP, or antithrombin III deficiency needing factor replacement, FFP, cryoprecipitate. Patient is on Warfarin and it is deemed necessary to maintain therapeutic INR (because the CP will reverse the warfarin effect). On dialysis at the time enrollment is considered. Active intracranial bleeding. Clinically significant myocardial ischemia. Prisoner or Incarceration Pregnancy or active breast feeding Has already received convalescent plasma 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intubated COVID-19 patients in the ICU<br>Mechanically ventilated intubated patients with respiratory failure due to COVID-19 | Biological: Multiple Doses of Anti-SARS-CoV-2 convalescent plasma<br>* Subjects to receive single or double plasma units infused on day 0 and potentially days 3 and 6.<br>* Other names: anti-SARS-CoV-2 convalescent plasma;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who consent to the study and receive at least one dose of convalescent plasma. | Feasibility of administering convalescent plasma to patients in the ICU who are intubated and mechanically ventilated due to COVID-19-induced respiratory failure will be assessed based on the proportion of subjects who consent and receive at least one dose of CP. The study will be declared 'feasible' if at least 80% of subjects who consent receive at least one dose. | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival of patients in the ICU receiving at least once dose of convalescent plasma for Covid-19-induced respiratory failure. | Overall survival (days, until Day 60). This will be quantified as number of trial patients alive at Day 60 after first dose of CP / total number of patients who received at least one dose of CP. | 60 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
convalescent plasma, Anti-Sars-COV-2 plasma