Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)

Agarwal, Anup; Mukherjee, Aparna; Kumar, Gunjan; Chatterjee, Pranab; Bhatnagar, Tarun; Malhotra, Pankaj; Agarwal, Anup; Mukherjee, Aparna; Kumar, Gunjan; Chatterjee, Pranab; Bhatnagar, Tarun; Malhotra, Pankaj; Latha, B; Bundas, Sunita; Kumar, Vivek; Dosi, Ravi; Khambholja, Janak Kumar; de Souza, Rosemarie; Mesipogu, Raja Rao; Srivastava, Saurabh; Dube, Simmi; Chaudhary, Kiran; Subash, S; Anbuselvi, S; Rajendran, V; Sundararajaperumal, A; Balamanikandan, P; Maheswari, R S Uma; Jayanthi, R; Ragunanthanan, S; Bhandari, Sudhir; Singh, Ajeet; Pal, Ashok; Handa, Anjali; Rankawat, Govind; Kargirwar, Ketan; Regi, Joyce; Rathod, Darshana; Pathrose, Edwin; Bhutaka, Nirankar; Patel, Mayur H; Verma, Rahul J; Malukani, Kamal; Patel, Shivani; Thakur, Apurv; Joshi, Satish; Kulkarni, Rashmi; Suthar, Nilay N; Shah, Nehal M; Purohit, Hemang M; Shah, Cherry K; Patel, Monila N; Shah, Saket; Shah, Smit T; Memon, Tehsim; Beriwala, Vishal R; Jashnani, Kusum; Ezzy, Fatema; Agrawal, Simran; Bhadade, Rakesh; Atish, MN; Madke, Tushar; Kavishwar, Vikas; Waghmare, Ramesh; Valvi, Nitin; Chander, B Thrilok; Sekhar, A Vinaya; Maurya, Akhilesh Kumar; Hemanth, K; Nagamani, K; Sudha, K; Chandra, T Ravi; Rao, K Tushara; Vyshnavi, J; Upadhyay, Rashmi; Bahadur, Shalini; Pathak, Rambha; Seth, Shikha; Gupta, Rakesh; Saxena, Rita; Dwivedi, Preksha; Malik, Reeni; Chourasia, Deepti; Lalwani, Jaya; Sharma, UM; Marko, JL; Suri, Amit; Kumar, Vijay; Kaushik, Rajnish; Kodan, Parul; Acharya, Bhabani Prasad; Gaur, Kuldeep Kumar; Gupta, Anubhav; Sachdeva, Prerna; Dogra, Shruti; Jindal, Aikaj; John, M Joseph; Dhanju, Avtar Singh; Khetrepal, Ranjana; Sharma, Neeraj; Kukar, Neetu; Kavita, Divya; Kumar, Rajesh; Mahajan, Rajesh; Singh, Gurpreet; Kaur, Jaspreet; Singh, Raminder Pal; Bassi, Rajni; Parikh, Swapneil; Shrivastav, Om; Shastri, Jayanthi; Desai, Maherra; Udupa, Shreevatsa; Bafna, Varun A; Barge, Vijay; Madane, Rajendra; Yadav, Sheetal; Misra, Sanjeev; Bajpayee, Archana; Garg, M K; Bohra, G K; Nag, Vijaylakshmi; Anne, Puneeth Babu; Nadeem, Mohd; Singh, Pallavi; Niwas, Ram; Khaire, Niranjan Shiwaji; Sharma, Rattiram; Singh, Mini P; Sachdeva, Naresh; Sachdev, Suchet; Hans, Rekha; Suri, Vikas; Yaddanapudi, LN; Lakshmi, PVM; Singh, Neha; Bhushan, Divendu; Kumar, Neeraj; Tambe, Muralidhar; Salvi, Sonali; Kadgi, Nalini; Sangle, Shashikala; Nakate, Leena; Joshi, Samir; Karyakarte, Rajesh; Goyanka, Suraj; Sharma, Nimisha; Verma, Nikhil; Das, Asim; Bahl, Monika; Wadhwa, Nitya; Bhat, Shreepad; Deshmukh, Shweta; Wagh, Vrushali; Kulkarni, Atul; Yardi, Tanvi; Kalgud, Ram S; Reddy, Purushottam; Yevoor, Kavitha; Gajula, Prashanth; Maleyur, Vivek; Medini, S; Mohith, HN; Gurtoo, Anil; Sud, Ritika; Pahuja, Sangeeta; Prakash, Anupam; Gogoi, Parijat; Shukla, Shailja; Reddy, D Himanshu; Chandra, Tulika; Pandey, Saurabh; Maurya, Pradeep; Ali, Wahid; Kumar, Vivek; Upadhyay, Kamlesh; Bhatnagar, Nidhi; Shah, Nilima; Shah, Mamta; Patel, Tarak; Jaiswal, Ram Mohan; Jain, Ashish; Sharma, Shweta; Rijhwani, Puneet; Gupta, Naveen; Patel, Tinkal C; Solu, Mahesh G; Patel, Jitendra; Shah, Yash R; Jarag, Mayur; Godbole, Varsha; Shah, Meenakshi; Raj, Rikin; Nagori, Irfan; Jha, Pramod R; Shah, Arti D; Yeeli, Gowtham; Jain, Archit; Gill, Rooppreet Kaur; Babu, KV Sreedhar; Babu, B Suresh; Mohan, Alladi; Vengamma, B; Sekhar, K Chandra; Damam, Srinivasulu; Narsimhulu, K; Aparna, C; Baleswari, G; Reddy, K Ravindranath; Chandrasekhar, P; Panjwani, Sunil Jodharam; Shah, Pragnesh H; Barvaliya, Manish; Desai, Kairavi; Akholkar, Pankaj J; Baldi, Milind; Yadav, Ashok; Gupta, Manoj; Rawat, Nitin; Chawda, Dilip; Natarajan, M; Sintha, M; Kumar, David Pradeep; Rabbani, Fathhur; Khadke, Vrushali Khirid; Patki, Dattatray; Marathe, Sonali; D’Souza, Clyde; Tadha, Vipul; Arora, Satyam; Gupta, Devendra Kumar; Dua, Seema; Chauhan, Nitu; Chahar, Ajeet Singh; Mammen, Joy John; Kumar, Snehil; Daniel, Dolly; Singh, Ravindraa; Dhat, Venkatesh; Agarwal, Yogesh; Arora, Sohini; Pathak, Ashish; Purohit, Manju; Sharma, Ashish; Sharma, Jayashree; Madkaikar, Manisha; Joshi, Kavita; Yadav, Reetika Malik; Bhagwat, Swarupa; Karnik, Niteen D; Gokhale, Yojana A; Naik, Leena; Margam, Sangita; Das, Santasabuj; Turuk, Alka; Kumar, V Saravana; Kanagasabai, K; Sabarinathan, R; Deshpande, Gururaj; Sharma, Sharda; Gunjikar, Rashmi; Shete, Anita; Phagiwala, Darpan; Patil, Chetan; Shingade, Snehal; Jarande, Kajal; Kaushal, Himanshu; Yadav, Pragya; Sapkal, Gajanan; Abraham, Priya

OBJECTIVE: To investigate the effectiveness of using convalescent plasma to treat moderate coronavirus disease 2019 (covid-19) in adults in India. DESIGN: Open label, parallel arm, phase II, multicentre, randomised controlled trial. SETTING: 39 public and private hospitals across India. PARTICIPANTS: 464 adults (≥18 years) admitted to hospital (screened 22 April to 14 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO(2)/FiO(2)) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 235 were assigned to convalescent plasma with best standard of care (intervention arm) and 229 to best standard of care only (control arm). INTERVENTIONS: Participants in the intervention arm received two doses of 200 mL convalescent plasma, transfused 24 hours apart. The presence and levels of neutralising antibodies were not measured a priori; stored samples were assayed at the end of the study. MAIN OUTCOME MEASURE: Composite of progression to severe disease (PaO(2)/FiO(2) <100 mm Hg) or all cause mortality at 28 days post-enrolment. RESULTS: 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 generalisability 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. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2020/04/024775.