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CTRI Number  CTRI/2020/04/024706 [Registered on: 17/04/2020] Trial Registered Prospectively
Last Modified On: 04/06/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Biological 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study
Modification(s)  
Effect of convalescent plasma in COVID-19 patients 
Scientific Title of Study   Efficacy of Convalescent Plasma Therapy in Severely Sick COVID-19 Patients: A Pilot Randomized Controlled Trial. 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
F.No.X.11026/74/2020-BD  DCGI 
NCT04346446  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Meenu Bajpai 
Designation  Additional Professor,Transfusion Medicine 
Affiliation  Institute of Liver and Biliary Sciences 
Address  D-1, Vasant Kunj New Delhi-110070

South West
DELHI
110070
India 
Phone  01146300000  
Fax  01146300025  
Email  meenubajpai@hotmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Meenu Bajpai 
Designation  Additional Professor,Transfusion Medicine 
Affiliation  Institute of Liver and Biliary Sciences 
Address  D-1, Vasant Kunj New Delhi-110070


DELHI
110070
India 
Phone  01146300000  
Fax  01146300025  
Email  meenubajpai@hotmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Meenu Bajpai 
Designation  Additional Professor,Transfusion Medicine 
Affiliation  Institute of Liver and Biliary Sciences 
Address  D-1, Vasant Kunj New Delhi-110070


DELHI
110070
India 
Phone  01146300000  
Fax  01146300025  
Email  meenubajpai@hotmail.com  
 
Source of Monetary or Material Support  
Institute of Liver & Biliary Sciences D-1,Vasant Kunj New Delhi-110070 
 
Primary Sponsor  
Name  Institute of Liver and Biliary Sciences 
Address  D-1,Vasant Kunj New Delhi-110070 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Meenu Bajpai  Institute of Liver and Biliary Sciences  D-1,Vasant Kunj New Delhi-110070
South West
DELHI 
01146300000
01146300025
meenubajpai@hotmail.com 
Dr Suresh Kumar  MAMC  2, Bahadur Shah Zafar Marg, Maulana Azad Medical College Campus, Balmiki Basti, New Delhi, Delhi 110002
Central
DELHI 
9891158991

drskumar31@yahoo.co.in 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
Institutional Ethics Committee  Approved 
Institutional Ethics Committee,ILBS  Approved 
Institutional Ethics Committee,MAMC  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  Convalescent Plasma with Supportive Care  200-600 mL convalescent plasma,single dose or into divided doses,intravenous for 1 to 7 days along with supportive care 
Comparator Agent  Random donor Plasma with Supportive Care  200-600 mL random donor plasma,single dose or into divided doses,intravenous for 1 to 7 days along with supportive care. Supportive Care will be based on symptomatic treatment 
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Recipient:
Severe COVID -19 infections defined as WHO Interim Guidance and the Guideline of Diagnosis and Treatment of COVID-19 of National Health Commission of China (version 5.0) with confirmation by real-time RT-PCR assay with severe disease i.e. meeting any 2 of the following criteria-
1. Respiratory distress, RR ≥30 beats/min
2. Oxygen saturation level less than 93% in resting state
3. Partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤ 300 mmHg.
4. Lung infiltrates > 50% within 24 to 48 hours
5. Very sick (on ventilator) and patients with co-morbidities such as patients with known co-
morbid diseases (COPD, CAD, CLD, CKD, cardiopulmonary disease-structural or valvular heart
disease)
6. Patient presenting with multi organ failure or requiring mechanical ventilation.
7. Minimum age: 18 yrs to maximum age- no limit as per recent protocol amendment.

Donor:
• Known case of recovered COVID-19 Infection, and
• Complete resolution of symptoms at least 28 days prior to donation or
Complete resolution of symptoms at least 14 days prior to donation and negative results for COVID-19 either from one or more nasopharyngeal swab specimens or by a molecular diagnostic test from the blood,
And
Negative RT-PCR for COVID-19 on two sequential paired nasopharyngeal and throat specimens > 24 hrs apart (WHO-CDC guideline).
• Donor Plasma after 2 negative tests and 2 weeks of remaining asymptomatic, without antibody titre & presence of IgG/IgM antibodies to COVID-19 by serological as per manufacturers instructions. Donors negative for these will be deferred).
• Fulfill all criteria of donor eligibility for donor Plasmapheresis under the Drugs & Cosmetics Act and Rules 1945, amended 11.03.2020. 
 
ExclusionCriteria 
Details  Recipient
• Patients with age less than 18 years.
• Pregnancy
• Individual with HIV and Hepatitis
• Morbid Obesity BMI>35 kg/m2
• Extremely moribund patients with an expected life expectancy of less than
24 hours.
• Failure to give informed consent from the patient or family members.
• Hemodynamic instability requiring vasopressors.
• Previous allergic history to plasma.

Donor:
• Donors age < 18 and ≥60 years old
• Do not fulfil all criteria of donor eligibility for donor Plasmapheresis under
the Drugs & Cosmetics Act and Rules 1945, amended 11.03.2020.
• Females who have been pregnant and previously transfused donors (to
prevent TRALI).
• Donors who have taken steroids during treatment for COVID-19. 
 
Method of Generating Random Sequence   Permuted block randomization, variable 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Proportion of patients remaining free of mechanical ventilation in both groups  day 7 
 
Secondary Outcome  
Outcome  TimePoints 
Mortality in both groups  day 28 
Improvement in Pa02/Fi02 ratio in both groups  day 2 and day 7 
Improvement in SOFA score in both groups  day 2 and day 7 
Duration of hospital Stay in both group.  day 28 
Duration of Intensive Care Unit stay in both groups.  day 28 
Requirements of Vasopressor in both groups.  day 28 
Days free of dialysis in both groups  day 28 
 
Target Sample Size
Modification(s)  
Total Sample Size="40"
Sample Size from India="40" 
Final Enrollment numbers achieved (Total)= "29"
Final Enrollment numbers achieved (India)="29" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)
Modification(s)  
21/04/2020 
Date of Study Completion (India) 30/05/2020 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="0"
Months="3"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   None Yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  

Currently, no effective treatments are available for the COVID-19 pandemic, which is related to more than 70,000 deaths all over the world. Scientists and Researchers are working on many aspects of treatment options for the development of vaccination and medication to combat this life-threatening problem. Convalescent plasma from recovered COVID-19 patients contains antibodies against COVID-19 which may be beneficial to severely sick COVID019 infected patients. We have planned a randomized controlled trial to assess the efficacy of this therapy in COVID-19 infected sick patients. We will collect up to 500 ml Convalescent Plasma from the COVID-19 infected recovered patient after 14 days of clinical and radiological recovery with two consecutive COVID-19 negative tests by PCR. We will further test the sample from the collected plasma for COVID-19 specific antibodies and their titer. This plasma will be frozen and sent to the treating center (MAMC). 200-600 ml of convalescent plasma will be transfused to patients who fit the eligibility criteria and are randomized to the convalescent plasma group. This will be done in severely sick patients. Data will be collected for the benefit and adverse events related to convalescent plasma transfusion.

For Donors:

Microtiter plates will be coated overnight at 4°C with 4 μg/mL recombinant SARS-CoV-2 RBD (receptor binding domain) proteins (50 μL per well). The plates will be washed 3 times with phosphate-buffered saline (PBS) containing 0.1% vol/vol Tween-20(PBST) and blocked with blocking solution (PBS containing 2% wt/vol nonfat dry milk) for 2 hours at 37 °C. The plates will be then washed with PBST. The serum samples will be diluted to 200-fold into PBS as initial concentration, and serial 3-fold dilutions of serum will be added to the wells and incubated at 37 °C for 60 minutes. After 3 washes, 100 μL of horseradish peroxidase-conjugated goat anti-human IgG (for IgG antibody titer detection)and IgM (for IgM antibody titer detection) antibodies solution will be added to each plate, respectively, and incubated at 37 °C for 60 minutes. After 5 washes, 100 μL of tetramethylbenzidine substrate will be added at room temperature in the dark. After 15 minutes, the reaction will be stopped with a2MH2SO4 solution (sulfuric acid). The absorbance will be measured at 450nm. All samples will be run in triplicate. The IgG titers will be determined by endpoint dilution.

Serum Neutralization Assay Vero cells (104) will be seeded 24 hours before the infection in a 96-well plate. On the day of infection, the cells will be washed twice. Serum samples from patients will be incubated at 56 °C for 30 minutes and then diluted 2-fold in cell culture medium (modified eagle medium). Aliquots (40 μL) of diluted serum samples (from2-fold to 2056-fold) will be added to 50 μL of cell culture medium containing 50 times the tissue culture infective dose (TCID50) of the virus strain on a 96-well plate and incubated at 37 °C for 2 hours in CO2 5% vol/vol. Virus antibody mix will be added to cells in 96-well plates and plates will be incubated at 37 °C with a microscopic examination for cytopathic effect after 5-day incubation. The highest dilution of serum that showed inhibition activity of SARS-CoV-2 will be recorded as the neutralizing antibody titer. Assays will be performed in triplicate with negative control samples from healthy volunteers.

For recipients:

The serum of each recipient will be obtained and enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers will be tested one day prior to the convalescent plasma transfusion. Changes of Receptor Binding Domain-Specific IgG titre and neutralizing antibody titers before and after convalescent plasma transfusion in patients will be obtained on day 0, day 1, day 3 and day 7. if possible.

All included patients would be randomized to receive either standard medical therapy (supportive therapy) with random donor plasma versus convalescent plasma and standard medical therapy Clinical information of all enrolled patients including symptoms at presentation, time to presentation to the hospital and development of pulmonary symptoms would be recorded. The details of comorbid diseases as measured by the Charlson index of comorbidity and Acute Physiology and Chronic Health Evaluation II (APACHE II). Details of cross-sectional imaging, chest-x-ray, bacterial or fungal co-infections and details of antibiotic treatment would be recorded. Development of complications including acute kidney injury, acute coronary syndrome, myocarditis, acute respiratory distress syndrome, and nosocomial infection will be recorded. The use of high-flow oxygen, non-invasive and invasive ventilation will follow standard guidelines and will be recorded. The details of antiviral treatment including oral oseltamivir, hydroxychloroquine, and use of intravenous steroids will be recorded for all enrolled patients.

 
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