Plasma Rich Antibodies From Recovered Patients From COVID19 (PRA-001)

Prospective interventional study, single arm of purified convalescent plasma transfusion as an add on therapy for the standard of care treatment (national guideline) (Oseltamivir (75mg/12 hours for 5-10 days) and hydroxychroquine (400mg twice in first day, 200 twice for 4-9 days) ± Azithromycin 500mg daily for 5 days

Study Overview

• Status: Unknown
• Conditions: Coronavirus Disease (COVID-19)
• Intervention / Treatment: Other: Antibody-Rich Plasma from COVID-19 recovered patients

Detailed Description

1. Selection of donor according to the eligibility criteria

   • Full medical history, concurrent medications, demographic data will be obtained.
   • Complete clinical assessment with special emphasis on assessment of resolution of symptoms
   • Body weight, height.
   • A confirmatory diagnostic test result (e.g., nasopharyngeal swab) at the time of illness or serological test for SARS-CoV-2 antibodies after recovery will be collected
   • COVID -19 PCR test by nasopharyngeal swab.
   • Complete blood count with differential counts
   • Viral screening (HBV, HCV, HIV & Syphilis): Conventional testing by chemiluminescence followed by nucleic acid testing (NAT)
   • Donor's written consent

2. Plasma collection:

   • Donor to be connected to microprocessor controlled plasmapheresis machine containing single use disposable kit for every donor.
   • A certain amount of blood is withdrawn by pump from the patient and immediately anticoagulated then centrifuged in the machine.
   • Blood components are separated into different layers according to the density of each component.
   • The plasma layer is collected and diverted into the collection bag while all other components are infused back to the patient, thus ending the first cycle.
   • Cycles are repeated until collecting a total of 400 ml of filtered plasma in the collection bag; that is one complete therapeutic dose for one patient in need.

3. Pathogen reduction/Viral inactivation by the Solvent/Detergent (S/D) method:

   • SD method is the gold standard for inactivation of enveloped viruses HBV, HCV and HIV. All these viruses have a lipid outer coat enveloping the nucleic acid.
   • Tri-N Butyl Phosphate (TNBP) acts as an organic solvent to remove lipids from the membranes of pathogens.Tween-20 is a non-ionic detergent that stabilizes TNBP and disrupts lipid bilayers, thus easing the extraction of lipids. Since the solvent is toxic, it is removed using a sterile vegetable oil (Castor oil).

4. Measuring remnants of TNBP:

   • By chromatography in Ain Shams Toxicology Center.
   • Concentration should be less than 10 ppm.

5. Screening phase for patients selection:

   • Obtaining informed consent: Written signed and dated informed consent will be obtained from each patient before being entered into the study. The investigator, or a person designated by the investigator, should fully inform the subject or, if the subject is unable to provide informed consent, the subject's legally acceptable representative, of all pertinent aspects of the trial. This will be obtained from each subject in accordance with the recommendation of the revised Declaration of Helsinki. The investigator will explain the nature, purpose and risks of the study. It will be clearly stated that the patient is free to withdraw from the study at any time for any reason without prejudice to future care, and with no obligation to give the reason for withdrawal.

   In case the patient is unable to provide his/her consent the legal guardian will give verbal approval on behaves of the patient and after he he/she will be well informed by the study design, procedure, risk and benefits over phone call.

   If it is difficult to reach the legal guardian, emergency approval will be obtained by Professional Legal Representative who will be the head authorities of the isolation hospital.

   • Full medical history, concurrent medications, demographic data will be obtained.
   • A thorough physical examination will be performed.
   • Body weight, height, BMI, vital signs (blood pressure, heart rate and temperature) and Blood oxygen saturation) will be recorded.
   • Chest x-ray and CT scan for chest will be recorded
   • Ventilation parameters to be recorded if ventilated
   • Laboratory to perform the following tests:

   Complete blood count with differential counts, Renal function tests (RFTs) (serum creatinine), Liver function tests (LFTs) (alanine amino transferase (ALT), aspartate amino transferase (AST), total and direct bilirubin), Coagulation test; prothrombin time and INR and D.dimer, HIV Ab, HCV Ab and HBV surface antigen (HBsAg), COVID -19 PCR test by nasopharyngeal swab. Urine pregnancy test for females.

6. Treatment phase for eligible patients:

   • Eligibility confirmed
   • Treatment with collected plasma in a dose of 400 ml on single therapeutic dose on Day1 as an add on therapy for the standard of care treatment (national guideline) (Oseltamivir (150mg/12 hours for 5-10 days) and hydroxychroquine (400mg twice in first day, 200 twice for 4-9 days) ± Azithromycin 500mg daily for 5 days.
   • The patient's health status, and the presence of adverse events will be assessed daily
   • Complete physical examination will be performed daily.
   • Vital signs (blood pressure, heart rate and temperature) will be recorded.
   • Follow-up CXR will be performed on daily and /CT scan will be performed as clinically indicated
   • Coagulation test; prothrombin time and INR and D.dimer will be re-reassessed on day 3, 7, and 14
   • HIV Ab, HCV Ab and HBV surface antigen (HBsAg) will be repeated at day 14
   • COVID -19 PCR test by nasopharyngeal swab will be repeated every 72 hours.

   • Post treatment period up to 30 days after end of treatment:

     • Vital signs (blood pressure, heart rate and temperature) will be recorded.
     • Symptoms and signs assessment will be done.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Non-US
    • Cairo, Non-US, Egypt, 11556
      • Faculty of Medicine Ain Shams University Research Institute- Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult 18 -80 years old
2. Must have laboratory confirmed COVID-19
3. Must have severe or immediately life-threatening COVID-19, Severe disease is defined as: Dyspnea,Respiratory frequency ≥ 30/min,Blood oxygen saturation ≤ 93%,Partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, and/or lung infiltrates > 50% within 24 to 48 hours Life-threatening disease is defined as: respiratory failure, septic shock, and/or multiple organ dysfunction or failure
4. Must provide informed consent by patient or his/her legal guardian or Professional Legal Representative

Exclusion Criteria:

• Patient with mild or moderate COVID-19
• Participation in any investigational clinical study, other than observational, within the past 30 days; or plans to participate in such a study at any time from the day of enrollment until 30 days post-treatment in the current study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Antibody-Rich Plasma; 400 millimeter of Antibody-Rich Plasma from COVID-19 recovered patients will be transfused to patients with severe or immediately life-threatening COVID-19	Other: Antibody-Rich Plasma from COVID-19 recovered patients; 400 millimeter of Antibody-Rich Plasma from COVID-19 recovered patients will be transfused to patients with severe or immediately life-threatening COVID-19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
viral COVID-19 clearance	Two successive negative COVID-19 PCR analysis tests 72 hours apart	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease of radiological abnormalities	The percentage of decrease of radiological abnormalities at day 14	14 days
Clinical improvement	Clinical improvement in form of normal body temperature for 48 hours	14 days

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 20, 2020
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 20, 2020
• Last Update Submitted That Met QC Criteria: April 17, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Egypt
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: FMASU P15/ 2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No