CTRI Number	CTRI/2020/04/024775 [Registered on: 21/04/2020] Trial Registered Prospectively
Last Modified On:	02/02/2021
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study Modification(s)	Biological
Study Design	Randomized, Parallel Group, Active Controlled Trial
Public Title of Study	Study to assess the efficacy and safety of convalescent plasma in moderate COVID-19 disease.
Scientific Title of Study	A Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease.
Secondary IDs if Any Modification(s)	Secondary ID  Registry  Protocol v 1.1 dated 12/04/20  Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)	Name  Dr Aparna Mukherjee  Address  Ansari Nagar, New Delhi New Delhi DELHI 110029 India  Phone     Fax     Email  aparna.sinha.deb@gmail.com
Details Contact Person Scientific Query Modification(s)	Name  Dr Anup Agarwal  Address  Ansari Nagar, New Delhi New Delhi DELHI 110029 India  Phone  8582932607   Fax     Email  mailanupagarwal@gmail.com
Details Contact Person Public Query Modification(s)	Name  Dr Anup Agarwal  Address  Ansari Nagar, New Delhi New Delhi DELHI 110029 India  Phone  8582932607   Fax     Email  mailanupagarwal@gmail.com
Source of Monetary or Material Support Modification(s)	Indian Council of Medical Research, Ansari Nagar, New Delhi-110029
Primary Sponsor	Name  Indian Council Of Medical Research  Address  Ansari Nagar, New Delhi  Type of Sponsor  Research institution
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 52   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Ravindra Singh  Aditya Birla Memorial Hospital  Aditya Birla Hospital Marg, Thergaon, Pimpri-Chinchwad, Maharashtra 411033 Pune   9011352331 Rpsingh008@gmail.com  Dr Neha Singh  AIIMS Patna   Aurangabad Rd, Phulwari Sharif, Patna, Bihar 801507 Patna   9993028936 drnehasingh@aiimspatna.org  Dr Archana Bajpayee  All India IAll India Institute of Medical Sciences Jodhpur  Basni Industrial Area, MIA 2nd Phase, Basni, Jodhpur, Rajasthan 342005 Jodhpur   8003996943 drarchanabajpai@yahoo.co.in  Dr Nitin M Nagarkar  All India Institute of Medical Sciences Raipur  Great Eastern Rd, AIIMS Campus, Tatibandh, Raipur, Chhattisgarh 492099 Raipur   07712572999 director@aiimsraipur.edu.in  Dr Nalini Kadgi  B.J. Government Medical College,  Jai Prakash Narayan Road, Railway Station Rd, Pune, Maharashtra 411001 Pune   9423007898 deanbjmcpune@gmail.com  Dr K J Upadhyay  B.J. Medical College and Civil hospital,  Asarwa, Ahmedabad, Gujarat, 380016 Ahmadabad   9825362253 drkjupadhyay@hotmail.com  Dr Ravi K  Bangalore Medical College and Research Institute  Krishna Rajendra Rd, Bengaluru, Karnataka 560002 Bangalore   9845128212 ravikdoc@gmail.com  Dr Ajay Goenka  Chirayu Medical College and Hospital Bhopal  Bhainsakhedi, Bairagarh, Bhopal, Madhya Pradesh 462030 Bhopal   9826040230 ajaygoenkachirayu@gmail.com  Dr Joy John Mammen  Christian Medical College Vellore  IDA Scudder Rd, Vellore, Tamil Nadu 632004 Vellore   9655503150 joymammen@cmcvellore.ac.in  Dr Nimisha Sharma  ESIC Medical College  NH-3, NIT Behind BK Hospital, Haryana 121012 Faridabad   9650682846 nims427@gmail.com  Dr CH Shrinivasa Rao  ESIC, Hyderabad  Sanath Nagar, Hyderabad 500038 Hyderabad   8106033420 srinivasarao.ch@esic.nic.in  Dr Simmi Dube  Gandhi Medical College Bhopal  Sultania Rd, near Hamidia Hospital, Royal Market, Medical College Campus, Kohefiza, Bhopal, Madhya Pradesh 462001 Bhopal   9479554822 simmi33@gmail.com  Dr Raja Rao  Gandhi Medical College Secunderabad  Gandhi Hospital, Musheerabad, Padmarao Nagar, Secunderabad, Telangana 500003 Hyderabad   9849010915 dr.mrrao@gmail.com  Dr Varsha Yogesh Godbole  GMERS Medical College, VAdodara  Old TB hospital Campus, Gotri Rd, Gotri, Vadodara, Gujarat 390021 Vadodara   9879181673 drvgodbole@gmail.com  Dr Saurabh Srivastava  Government Institute of Medical Sciences Greater Noida   Greater Noida, Uttar Pradesh 201310 Gautam Buddha Nagar   9654233158 saurabhsrivas@gmail.com  Dr Sunil Panjwani  Government Medical College Bhavnagar  Bus Stand, near State Road Transport Corporation, Panwadi, Bhavnagar, Gujarat 364001 Bhavnagar   9825331039 spanjwani0@gmail.com  Dr Sushant Meshram  Government Medical College Nagpur  Hanuman Nagar, Ajni Rd, Medical Chowk, Ajni, Nagpur, Maharashtra 440003 Nagpur   9860990379 drsushant.in@gmail.com  Dr Tinkle Patel  Government Medical College Surat  Opp. Income Tax Department Office, Majura Gate, Surat, Gujarat 395001 Surat   9898713223 pateltinkal@yahoo.com  Dr Chennaveerappa PK  Hassan Institute of Medical Sciences  Hassan Institute of Medical Sciences, Sri Chamarajendra Hospital Campus, Krishnaraja Pura, Hassan, Karnataka 573201 Hassan   9480303972 drchennamd@yahoo.com  Dr B Abhishek  Jawaharlal Institute of Postgraduate Medical Education & Research Puducherry  Jipmer Campus Rd, Gorimedu, Dhanvantari Nagar, Puducherry, 605006 Pondicherry   9008255888 drabhigowda@gmail.com  Dr Ram Kalgud  Karnataka Institute of Medical Sciences Hubli  PB Rd, Vidya Nagar, Hubli, Karnataka 580022 Dharwad   9844426887 drkaulgud.kims@gmail.com  Himanshu Reddy  King George Medical University Lucknow  Shah Mina Rd, Chowk, Lucknow, Uttar Pradesh 226003 Lucknow   9839266822 placid2020kgmu@gmail.com  Dr K Narasmhulu  Kurnool Medical College.  Near Bhudawarapet Bharath Petroleum, Kisan Ghat Rd, Kurnool, Andhra Pradesh 518002 Kurnool   8978285266 nara17kg@gmail.com  Dr Anil Gurtoo  Lady Hardinge Medical College Delhi  Connaught Place, New Delhi, Delhi 110001 Central   9810255153 anilgurtoo2@gmail.com  Dr Niteen Karnik  Lokmanya Tilak Municipal General Hospital.  Dr Babasaheb Ambedkar Rd, RB2 Central Railway Quarters, Sion West, Sion, Mumbai, Maharashtra 400022 Mumbai   9821483404 drndkarnik@hotmail.com  Dr B Latha  Madras Medical College  Near Park Town, Park Town, Chennai, Tamil Nadu 600003 Chennai   9840313152 latsbalu@yahoo.co.uk  Dr M Natrajan  Madurai Medical College  Collector Office Road Near, Alwarpuram, Madurai, Tamil Nadu 625020 Madurai   9842150275 laknataj@yahoo.com  Dr Ram Manohar Jaiswal  Mahatma Gandhi Medical College and Hospital Jaipur  Tonk Rd, near India International School, Ricco Industrial Area, Sitapura, Jaipur, Rajasthan 302022 Jaipur   09602779900 drrmjaiswal@mgumst.org  Dr Millind Baldi  Mahatma Gandhi Memorial Medical College Indore  AB Rd, CRP Line, Indore, Madhya Pradesh 452001 Indore   9869393107 milindbaldi@gmail.com  Dr Shivakumar KM  Mandya Institute of Medical Sciences  Mandya Institute of Medical Sciences, Bangalore-Mysore Road, Mandya, Karnataka 571401 Mandya   9448345267 pulseshivu@yahoo.com  Dr J Inbanthan  Mysore Medical College  Mysuru, Karnataka India 57000 Mysore   9448051826 jinathan2008@gmail.com  Dr Arti Trivedi  PDU Government Medical College  Jam Tower, Jamnagar Road Opp, Chawk, Kothi Compound, Rajkot, Gujarat 360001 Rajkot   9824206541 aartitrivedi@gmail.com  Dr Vrushali Khadke  Poona Hospital and Research Centre  Shivam, 27, Shivram Matre Rd, Nr. Alka Talkies, Ganjwe Wadi, Sadashiv Peth, Pune, Maharashtra 411030 Pune   9822407783 vgkhadke@gmail.com  Dr Pankaj Malhotra  Postgraduate Institute of Medical Education and Research Chandigarh  Madhya Marg, Sector 12, Chandigarh, 160012 Chandigarh   7087009680 malhotrapankaj@hotmail.com  Dr A Murali  PSG Institute of Medical Sciences & Research Coimbatore  Avinashi Rd, Peelamedu, Anna Nagar, Coimbatore, Tamil Nadu 641004 Coimbatore   9941356856 Muralimd2000@gmail.com  Dr Manju Purohit  R D Gardi Medical College  Ujjain, Madhya Pradesh 456001 Ujjain   7987114919 manjuraj.purohit64@gmail.com  Dr Varun Ashok Bafna  Rajarshee Chhatrapati Shahu Maharaj Government Medical College and CPR Hospital Kolhapur  Shenda Park Rd, Shenda Park, Kolhapur, Maharashtra 416013 Kolhapur   9422415378 drvarunbafna6@gmail.com  Dr Kiran Chaudhary  Ram Manohar Lohia Hospital  Baba Kharak Singh Rd, near Gurudwara Bangla Sahib, Connaught Place, New Delhi, Delhi 110001 New Delhi   9560095404 drchaudharyk@yahoo.co.in  Dr Anjali Sharma  Safdarjung Hospital.  Ring Road,Safdarjung West, Safdarjung Campus, Ansari Nagar East, New Delhi, Delhi 110029 New Delhi   9560109165 anjalisharmapath@gmail.com  Dr Anupam Verma  Sanjay Gandhi Postgraduate Institute of Medical Sciences  New PMSSY Rd, Raibareli Rd, Lucknow, Uttar Pradesh 226014 Lucknow   9415419882 aver2211@gmail.com  Dr Aikaj Jindal  Satguru Pratap Singh Hospital Ludhiana  Grand Trunk Rd, Sherpur Chowk, Sherpur, Ludhiana, Punjab 141001 Ludhiana   9803002423 drjindalaikaj@gmail.com  Dr Jayashree Sharma  Seth Gordhandas Sunderdas Medical College (GSMC) and the King Edward Memorial Hospital  Acharya Donde Marg, Parel Mumbai 400012 Pune   8080034525 jayashreesharma@kem.edu  Dr Vivek Kumar  Sir H. N. Reliance Foundation Hospital and Research Centre Mumbai  , Prarthana Samaj, Raja Rammohan Roy Rd, Charni Road East, Khetwadi, Girgaon, Mumbai, Maharashtra 400004 Mumbai   9833731099 Vivek57.kumar@rfhospital.org  DR Sunita Bundas  SMS Medical College Hospital,Jaipur  Department of Immunohematology and Transfusion Medicine, Jaipur Jaipur   9414045723 drsunitabundas@yahoo.in  Dr Sreepad M Bhat  Smt Kashibai Navale Medical College  S.No. 49/1, Off Mumbai - Pune Bypass, Narhe, Pune, Maharashtra 411041 Pune   9850470067 smb.med@gmail.com  Dr J R Khambolja  Smt NHL Municipal Medical College  Department of Medicine, Ellisbridge, Ahmedabad, Gujarat 380006 Ahmadabad   9825447813 kham_jak@yahoo.co.in  Dr Ravi Dosi  Sri Aurobindo Institute of Medical Sciences  Indore - Ujjain State Highway, near MR 10, Crossing, Indore, Madhya Pradesh 453555 Indore   7869036808 ravi.dosi@gmail.com  Dr Sreedhar Babu  Sri Venkateswara Institute of Medical Sciences  Alipiri Road, Tirupati, Chittoor District, Andhra Pradesh- 517507 Chittoor   9494403546 kinneravsb@gmail.com  Pramod R Jha  Sumandeep Vidyapeeth and Institution and Dhiraj Hospital  At & Po. Pipariya, Taluka Waghodia, Dist, Gujarat 391760 Vadodara   9426256118 dr.pkrnj@gmail.com  Dr Satyam Arora  Super Speciality Paediatric Hospital and Post Graduate Teaching Institute Noida  Indergarhi, Sector 30, Noida, Uttar Pradesh 201310 Gautam Buddha Nagar   9971107774 satyamarora83@gmail.com  Dr S A Manimala  Tirunelveli Medical College Hospital  High Ground Rd, Palayamkottai, Tirunelveli, Tamil Nadu 627011 Tirunelveli   9843193801 dr.sa.manimala@gmail.com  Dr Rosemarie D Souza  TMC & BYL Nair Hospital Kasturba Hospital Mumbai  Dr. A. L. Nair, Road,Mumbai - 400008 Mumbai   9820056230 drrosemariedesouza@gmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 52   Name of Committee  Approval Status  ABVIMS & Dr.RML Hospital  Approved  Aditya Birla Memorial Hospital Pune  Approved  AIIMS Patna  Approved  AIIMS RAIPUR  Approved  All India Institute of medical science ,Jodhpur  Approved  B.J. Government Medical College,Pune  Approved  B.J. Medical College and Civil Hospital, Ahmedabad  Approved  Banglore Medical College and Research Institute   Approved  Christian Medical College Vellore  Approved  ESIC Hyderabad  Approved  Gandhi Medical College, Bhopal  Approved  Gandhi Medical College, Bhopal  Approved  Gandhi Medical College, Secunderabad  Approved  GMERS Vadodara  Approved  Government Institute of Medical Sciences, Gr Noida  Approved  Government Medical College, Bhavnagar  Approved  Government Medical College, Surat  Approved  Government Medical college. Hanuman Nagar,Nagpur  Approved  HIMS Hassan  Approved  Institutional Ethics Committee SMS Jaipur  Approved  JIPMER  Approved  Karnataka Institute of Medical Sciences, Hubli  Approved  King george medical University Lucknow  Approved  Kurnool Medical College kurnool andhra pradesh  Approved  LHMC Delhi  Approved  Lokmanya Tilak Municipal Medical College and General Hospital  Approved  Madras Medical College.Chennai  Approved  Madurai Medical College, Madurai.  Approved  Mahatma Gandhi Medical College and Hospital,Jaipur  Approved  Mahatma Gandhi Memorial Medical College, Indore  Approved  MIMS Mandya  Approved  Mysore Medical College  Approved  P.D.U.Medical College, Rajkot  Approved  Poona Hospital and Research Centre, Pune  Approved  Postgraduate Institute of Medical Education and Research, Chandigarh  Approved  PSG Institute of Medical Sciences & Research  Approved  R.D.Gardi Medical College , Ujjain  Approved  Rajarshee Chhatrapati Shahu Maharaj Government Medical College and CPR Hospital, Kolhapur  Approved  SAIMS Hospital ,Indore (M.P)  Approved  Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow  Approved  Satguru Pratap Singh Hospital, Ludhiana  Approved  Seth GS Medical College and KEM Hospital,Mumbai , Maharastra   Approved  Sir H. N. Reliance Foundation Hospital and Research Centre, Mumbai  Approved  Smt .Kashibai Navale Medical College and General Hospital   Approved  Smt NHL Municipal Medical College, Ahmedabad  Approved  sri venkateswara institute of medical science   Approved  SSPH Noida  Approved  Sumandeep Vidyapeeth Institutional Ethics Committee  Approved  T.N. Medical College & BYL Nair Hospital  Approved  Tirunelvelli Medical College   Approved  Translational health science and technology institute   Approved  VMMC and Safdurjung MC  Approved
Regulatory Clearance Status from DCGI	Status  Approved/Obtained
Health Condition / Problems Studied Modification(s)	Health Type  Condition  Patients  Coronavirus as the cause of diseases classified elsewhere
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Intervention  Convalescent plasma   Convalescent plasma, 2 doses of 200 mL each, from recovered COVID-19 patient.  Comparator Agent  Usual care for COVID-19 disease  Usual care for COVID-19 disease
Inclusion Criteria	Age From  18.00 Year(s) Age To  90.00 Year(s) Gender  Both  Details  1. Patients admitted with RT-PCR confirmed COVID-19 illness. 2. Age > 18 years 3. Has any of the two a. PaO2/ FiO2: 200-300 b. Respiratory Rate > 24/min and SaO2 < 93% on room air 4. Availability of matched donor plasma at the point of enrolment
ExclusionCriteria	Details  1. Pregnant women 2. Breastfeeding women 3. Known hypersensitivity to blood products 4. Receipt of pooled immunoglobulin in last 30 days 5. Critically ill patients: a. P/F ratio <200 (moderate - severe ARDS) b. Shock 6. Participating in any other clinical trial 7. Clinical status precluding infusion of blood products
Method of Generating Random Sequence	Stratified randomization
Method of Concealment	Centralized
Blinding/Masking	Not Applicable
Primary Outcome Modification(s)	Outcome  TimePoints  The primary outcome is a composite measure of the avoidance of - 1. Progression to severe ARDS (P/F ratio 100) or 2. All-cause Mortality at 28 days   28 days from intervention
Secondary Outcome	Outcome  TimePoints  1. Time to symptom resolution a. Fever b. Shortness of Breath c. Fatigue   1,3,5,7,14 days  5. Duration of respiratory support required a. Duration of Invasive Mechanical Ventilation b. Duration of Non-Invasive   5. Duration of respiratory support required a. Duration of Invasive Mechanical Ventilation b. Duration of Non-Invasive   Adverse events (AE) associated with transfusion  Adverse events (AE) associated with transfusion  Change in oxygen requirement post transfusion  0,1,3,5,7,14  Change in SOFA pre and post transfusion  0,1,3,5,7,14  Correlation between IgG antibody in donor plasma and recipient plasma after transfusion.  0, 1,3,7  Correlation between viral neutralization titer and Elisa antibody assay in donor plasma   Correlation between viral neutralization titer and Elisa antibody assay in donor plasma   Length of hospital stay  Length of hospital stay  Levels of bio-markers (CRP, IL6, Ferritin) pre and post transfusion  0, 3  Need of Vasopressor use  Need of Vasopressor use  Pre and post transfusion antibody titers (IgG) in recipient plasma   0,3,7 days  Radiological improvement  0,3,7 days  To measure the change in RNA levels (Ct values) of SARS-CoV-2 from RT-PCR transfusion]  Days 0, 3, and 7
Target Sample Size	Total Sample Size="452" Sample Size from India="452"
Phase of Trial	Phase 2
Date of First Enrollment (India) Modification(s)	22/04/2020
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="0" Months="6" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Completed
Publication Details Modification(s)	Agarwal Anup, Mukherjee Aparna, Kumar Gunjan, Chatterjee Pranab, Bhatnagar Tarun, Malhotra Pankaj et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial) BMJ 2020; 371 :m3939
Brief Summary Modification(s)	The novel coronavirus disease (COVID-19), which began in Wuhan, China, in December 2019, has been declared to be a pandemic by the World Health Organization (WHO). Although not completely understood, multiple pathophysiological mechanisms have been hypothesized for the cause of mortality in COVID-19. Currently, there are no approved treatments for COVID-19. Multiple trials are being done across the globe to assess the efficacy of various treatment strategies.  In a small case series, five critically ill COVID-19 patients with ARDS were treated with convalescent plasma containing neutralizing antibodies. Infusion of plasma was followed by improvement in clinical status in all five patients.We hypothesize that the use of convalescent plasma will limit the progression of disease in patients with moderate COVID-19 infection. we plan to conduct a multi-center randomized controlled trial to test this hypothesis. The patients included will be those with RT-PCR confirmed COVID-19 illness, Age > 18 years, Has any of the two: a. PaO2/ FiO2: 200-300 b. Respiratory Rate > 24/min and SaO2 < 93% on room air;   Availability of matched donor plasma at the point of enrolment. After obtaining informed consent and randomization, the intervention arm will receive 2 doses of 200mLeach of convalescent plasma along with usual care whereas the control group will receive usual care for COVID-19. The primary outcome is a composite measure of the avoidance of- Progression to severe ARDS (P/F ratio <100) or all-cause mortality at 28 d.   Brief result Progression to severe disease or all cause mortality at 28 days after enrolment occurred in 44 (19%) participants in the intervention arm and 41 (18%) in the control arm (risk difference 0.008 (95% confidence interval −0.062 to 0.078); risk ratio 1.04, 95% confidence interval 0.71 to 1.54).   Conclusion Convalescent plasma was not associated with a reduction in progression to severe covid-19 or all cause mortality. This trial has high generalizability and approximates convalescent plasma use in real life settings with limited laboratory capacity. A priori measurement of neutralising antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of covid-19.