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
|
|
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
|
|
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. |