Experimental Use of Convalescent Plasma for Passive Immunization in Current COVID-19 Pandemic in Pakistan in 2020

Experimental Use of Convalescent Plasma of Passive Immunisation In Current COVID-19 Pandemic in Pakistan in 2020 Rationale & Objective: This study would help to gather real-life setting clinical data in local population, ultimately leading to increased evidence based management of the disease condition in the said population.

Eligibility:

1. informed consent must have been obtained
2. confirmed COVID-19 cases confirmed by RT-PCR laboratory tests

3. moderately severe or severe life-threatening COVID-19 related features: a) Moderately Severe disease as defined by the following features: i) Shortness of breath, ii) respiratory rate ≥ 30/min, iii) arterial blood oxygen saturation ≤ 92%, iv) and/or lung infiltrates > 25% within 24 to 48 hours 67 b) Severe Life-threatening disease as defined by: i) respiratory failure, ii) shock, and/or § multiple organ dysfunction

   Exclusion Criteria:

   Allergy history of plasma, sodium citrate and methylene blue; 2. For patients with history of autoimmune system diseases or selective IgA deficiency, 3. the application of convalescent plasma should be evaluated cautiously by clinicians.

4. Patients having evidence of uncontrolled cytokine release syndrome leading to end-stage multiorgan failure.

Methodology:

Total sample size is n=2000. A case report form (CRF) will have to be generated for each corona virus patient at baseline and the completion of study endpoint (at the time of discharge and at 4 weeks after experimental treatment modality using convalescent plasma.

• A unique identification number will be issued for each patient in this protocol.
• This data will be recorded in the national database. Data sources & Analysis: Patient data originating from patient medical record and assessments (mentioned in table below) will be recorded in the study CRF. Safety data (AEs and SAEs) from any time point during the study will be recorded in the study CRF. All analyses will be performed by third party statistician on SPSS. For continuous variables, summary statistics included n (number of observations), mean, standard deviation, median, minimum and maximum values, as well as frequencies and percentages for categorical variables will be presented.

Study Overview

• Status: Unknown
• Conditions: Covid-19
• Intervention / Treatment: Other: convalescent plasma

Detailed Description

Passive immunization involves the administration of antibodies against a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease due to that agent. A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease. When used for therapy, antibody is most effective when administered shortly after the onset of symptoms. The reason for temporal variation in efficacy is not well understood but could reflect that passive antibody works by neutralizing the initial inoculums, which is likely to be much smaller than that of established disease. As an example, passive antibody therapy for pneumococcal pneumonia was most effective when administered shortly after the onset of symptoms, and there was no benefit if antibody administration was delayed past the third day of disease.

The therapeutic benefits of convalescent plasma were formally studied in animal models in early 20th century. It efficacy was first determined in 1916, when 26 poliomyelitis patients were treated with convalescent plasma from polio survivors. Subsequently, therapeutic and prophylactic significance was explored in influenza and measles. Transfusion of immune plasma is a standard treatment modality for various viral hemorrhagic fevers. Its efficacy in treating Ebola Virus Disease is also well established. Studies have reported reduction viral load in patients with H1N1 influenza. Of special attention is the meta-analysis, carried out by Mair-Jenkinset al, concluding effectiveness of passive immunization as a treatment option for severe viral acute respiratory infections caused by SARS corona virus, influenza A (H1N1), avian influenza A (H5N1) and Spanish influenza A. Efficacy of convalescent plasma has been anecdotally reported in SARS-CoV-2 infections.

• Study Type: Interventional
• Enrollment (Anticipated): 2000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 75300
      • Recruiting
      • National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)
      • Contact: Dr. Arshi Naz; Phone Number: 00923232234376; Email: labarshi@yahoo.com
      • Sub-Investigator: Professor Javed Akram
      • Sub-Investigator: Professor Bikha Ram Deverajani
      • Sub-Investigator: Dr Arshi Naz
      • Sub-Investigator: Professor Shahtaj Masood Khan
      • Sub-Investigator: Professor Faridoun
      • Sub-Investigator: Professor Ikram Din Ujjan
      • Sub-Investigator: Dr Lubna Meraj

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

FOR DONORS:

1. Volunteer enrolment (Informed consent will be obtained; Annexures-2A & 2B).
2. All the regulations related to ICH-GCP and Blood Transfusion Authority (BTA) Pakistan will be followed.
3. Should fulfill all the criteria of a healthy blood donor (with the exception of history of COVID-19 during last 4-8 weeks.
4. History of COVID-19 during last 4-8 weeks
5. RT-PCR negative for SARS-CoV-2 RNA (carried out on nasopharyngeal or oropharyngeal specimen)
6. Age cutoff: 18-55years
7. Body weight cut off: >50 kg for men and > 45kg for women

FOR RECIPIENTS:

1. Volunteer enrolment (Informed consent will be obtained; Annexures-3A & 3B).
2. Confirmed COVID-19 cases confirmed by RT-PCR laboratory tests

3. Severe or Critical COVID-19 related features (8):

   a. Severe COVID-19, defined by the presence of any of the following features: i. Shortness of breath ii. Respiratory rate ≥ 30/min, iii. Arterial blood oxygen saturation ≤ 93%, iv. Lung infiltrates > 50% within 24 to 48 hours b. CriticalCOVID-19, defined by the presence of any of the following features: i. Respiratory failure, ii. Shock iii. Multiple organ dysfunction

Exclusion Criteria:

1. Allergy history for plasma, sodium citrate and methylene blue
2. For patients with history of autoimmune system diseases or selective IgA deficiency, the application of convalescent plasma should be evaluated cautiously by clinicians.
3. Patients having evidence of uncontrolled cytokine release syndrome leading to end-stage multi organ failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Arm; Intervention: Convalescent plasma (Frozen Solution for infusion) obtained from COVID-19 recovered patients. The dosage depends upon the clinical situation and underlying disorder. Children: 15 ml/kg over 4-6 hours once in patients under 35 kg body weight. Adults: maximum 450 - 500 ml over 4-6 hours once in all adults patients.	Other: convalescent plasma; Plasmapheresis, 900 - 1000 mL each time.; Standard apheresis plasma collection protocol using Haemonetics MCS+ intermittent blood flow system or Terumo Optia, Cobe-Spectra, Trima or Fresenius continuous flow system to be used.; Isovolumic saline replacement should be done.; Each donor can donate convalescent plasma again after an interval of every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in COVID-19 severity status	Improvement in disease severity will be regarded as a shift from Critical to Severe or from Severe to Mild disease category. The various disease categories are defined as following (17): Mild COVID-19, defined by the absence of features given in criteria for moderate and severe disease.; Severe COVID-19, defined by the presence of any of the following features: i. Shortness of breath ii. Respiratory rate ≥ 30/min, iii. Arterial blood oxygen saturation ≤ 93%, iiii. Lung infiltrates > 50% within 24 to 48 hours c. Critical COVID-19, defined by the presence of any of the following features: i. Respiratory failure, ii. Shock iii. Multiple organ dysfunction	Up to 09 days

Collaborators and Investigators

• Sponsor: Hilton Pharma
• Investigators: Principal Investigator: Dr. Tahir Shamsi, FRCP MRCPath, National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)

Publications and helpful links

General Publications

• Casadevall A, Scharff MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother. 1994 Aug;38(8):1695-702. doi: 10.1128/AAC.38.8.1695. No abstract available.
• Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.
• Robbins JB, Schneerson R, Szu SC. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis. 1995 Jun;171(6):1387-98. doi: 10.1093/infdis/171.6.1387.
• Luke TC, Casadevall A, Watowich SJ, Hoffman SL, Beigel JH, Burgess TH. Hark back: passive immunotherapy for influenza and other serious infections. Crit Care Med. 2010 Apr;38(4 Suppl):e66-73. doi: 10.1097/CCM.0b013e3181d44c1e.
• Khan TNS, Mukry SN, Masood S, Meraj L, Devrajani BR, Akram J, Fatima N, Maqsood S, Mahesar A, Siddiqui R, Ishaque S, Afzal MB, Mukhtar S, Ahmed S, Naz A, Shamsi TS. Usefulness of convalescent plasma transfusion for the treatment of severely ill COVID-19 patients in Pakistan. BMC Infect Dis. 2021 Sep 27;21(1):1014. doi: 10.1186/s12879-021-06451-7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2020
• Primary Completion (ANTICIPATED): April 1, 2021
• Study Completion (ANTICIPATED): April 1, 2021

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (ACTUAL): April 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• 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
• Other Study ID Numbers: PIPK- 0000 /NIBD-0000/2020

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