Evaluating the safety and efficacy of recombinant human thrombopoietin among severe sepsis patients with thrombocytopenia: study protocol for a randomized controlled trial.

Qin Wu,Ranran Li,Zhiwu Hong,Xiuwen Wu,Jieshou Li,Huajian Ren,Song Liu,Min Yao,Gefei Wang,Dong Hu,Yuan Li,Yunzhao Zhao,Jun Chen,Jianan Ren,Guosheng Gu,Gunawei Li

doi:10.1186/s13063-015-0746-6

Abstract

BackgroundSepsis 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/DesignThe 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.DiscussionTo 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.Trial registrationClinicalTrials.gov: NCT02094248. Registration date: 23 March 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0746-6) contains supplementary material, which is available to authorized users.

Highlights

Sepsis is still a major health problem that causes high mortality in all populations
Researches have suggested that the declining platelet counts (PCs) are associated with mortalities among sepsis patients caused by various diseases, indicating the importance of recovering from thrombocytopenia during sepsis [5, 6]
Our previous study demonstrated that administration of recombinant human thrombopoietin with conventional medical therapies could significantly improve the PCs in severe sepsis patients with thrombocytopenia and effectively reduce the platelet transfusion possibility [11]

Summary

Discussion

This study is designed as an open-label study and physiological serum is used as a placebo. The detailed reviewer’s comments and the author’s reply can be found in Additional file 4. To our knowledge, this is the first study to evaluate the safety and efficacy of rhTPO among severe sepsis patients with thrombocytopenia in a varied population. Additional file 4: The reviewer’s comments and the author’s reply. QW, GW, GG, and JC contributed to the conception and design, critical revision and final approval of the manuscript. XW, GL, ZH, HR, RL and YL contributed to the design, critical revision and final approval of the manuscript. JL and YZ contributed to the conception and design, manuscript writing and final approval of the manuscript.

Background

Methods