David C Lye1, Sophia Archuleta2, Sharifah F Syed-Omar3, Jenny G Low4, Helen M Oh5, Yuan Wei6, Dale Fisher2, Sasheela S L Ponnampalavanar3, Limin Wijaya7, Linda K Lee8, Eng-Eong Ooi9, Adeeba Kamarulzaman3, Lucy C Lum3, Paul A Tambyah2, Yee-Sin Leo10. 1. Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: david_lye@ttsh.com.sg. 2. Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Infectious Diseases, National University Hospital, National University Health System, Singapore. 3. University Malaya Medical Centre, Kuala Lumpur, Malaysia. 4. Singapore General Hospital, Singapore; Duke-NUS Medical School, Singapore. 5. Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Changi General Hospital, Singapore. 6. Singapore Clinical Research Institute, Singapore. 7. Singapore General Hospital, Singapore. 8. Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore. 9. Duke-NUS Medical School, Singapore. 10. Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Lee Kong Chian School of Medicine, Singapore.
Abstract
BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia. METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed. FINDINGS:Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported. INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events. FUNDING: National Medical Research Council, Singapore.
RCT Entities:
BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia. METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed. FINDINGS: Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported. INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events. FUNDING: National Medical Research Council, Singapore.
Authors: Kevin John John; Karthik Gunasekaran; John Davis Prasad; Divya Mathew; Sohini Das; N Sultan; Asha Mary Abraham; Ramya Iyyadurai Journal: Interdiscip Perspect Infect Dis Date: 2019-09-04
Authors: Kay M Tomashek; Bridget Wills; Lucy Chai See Lum; Laurent Thomas; Anna Durbin; Yee-Sin Leo; Norma de Bosch; Elsa Rojas; Kim Hendrickx; Martin Erpicum; Liane Agulto; Thomas Jaenisch; Hasitha Tissera; Piyarat Suntarattiwong; Beth Ann Collers; Derek Wallace; Alexander C Schmidt; Alexander Precioso; Federico Narvaez; Stephen J Thomas; Robert Edelman; João Bosco Siqueira; M Cristina Cassetti; Walla Dempsey; Duane J Gubler Journal: PLoS Negl Trop Dis Date: 2018-10-04