title: Evaluating the safety and efficacy of recombinant human thrombopoietin among severe sepsis patients with thrombocytopenia: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Sepsis is still a major health problem that causes high mortality in all populations. Organ dysfunction including sepsis-associated thrombocytopenia is prevalent among sepsis patients, resulting in increasing mortality rates. Considering the clinical role of platelets, thrombocytopenia in sepsis has led to a large spend in research activity and clinical trials in this area, yet there is no consensus upon which treatment should be administered. As a result, platelet transfusion is often indicated to resolve low platelet counts, leading to an increasing risk of the multiple risks transfusion brings, such as infectious or immune system complications. Given the role of thrombopoietin in stimulating proliferation and differentiation of megakaryocytes, our previous study investigated the potential benefits of recombinant human thrombopoietin in severe sepsis patients with thrombocytopenia. However, there are several limitations in the study, which may have led to bias in our conclusion. Thus, we are conducting this study in order to evaluate the safety and efficacy of recombinant human thrombopoietin in a large, varied population.
  
  
  METHODS
  The study is designed as a randomized, open-label, placebo-controlled, multi-center study in tertiary academic centers for evaluating the safety and efficacy of recombinant human thrombopoietin over placebo. An established total of 708 patients with sepsis and thrombocytopenia will undergo prospective random assignment to recombinant human thrombopoietin or placebo (a 1:1 ratio). The primary endpoint is 7-day all-cause mortality and 28-day all-cause mortality.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to evaluate the safety and efficacy of recombinant human thrombopoietin among severe sepsis patients with thrombocytopenia in a varied population. With our study, the level of evidence for the treatment of these patients will be significantly raised.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT02094248 . Registration date: 23 March 2014.
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. qinwu0221@gmail.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. jiananr@gmail.com.
authors.forename: Jianan
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. wgfwang@gmail.com.
authors.forename: Gefei
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. guguoshengde@163.com.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Gu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. hdalce@126.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. Medical.Lis@gmail.com.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. li.guanwei@foxmail.com.
authors.forename: Gunawei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. yccjun@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. doublerans@hotmail.com.
authors.forename: Ranran
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. zhwhong1986@163.com.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. rhj1288@163.com.
authors.forename: Huajian
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. lygwxw@163.com.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. 595037340@qq.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, VA Medical Center, 830 Chalkstone Avenue, Providence, RI, 02908, USA. minyao99@hotmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. yzzhaomd@gmail.com.
authors.forename: Yunzhao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China. jieshou_li@163.com.
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D002681:China; D002985:Clinical Protocols; D006801:Humans; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism; D010976:Platelet Count; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D018401:Sample Size; D018805:Sepsis / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D034061:Thrombopoiesis / Q000187:drug effects*; D013926:Thrombopoietin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D013926:Thrombopoietin