The effect of recombinant human thrombopoietin (rhTPO) on sepsis patients with acute severe thrombocytopenia: a study protocol for a multicentre randomised controlled trial (RESCUE trial)

Zhigang Zhou, Tienan Feng, Yun Xie, Peijie Huang, Hui Xie, Rui Tian, Biyun Qian, Ruilan Wang, Zhigang Zhou, Tienan Feng, Yun Xie, Peijie Huang, Hui Xie, Rui Tian, Biyun Qian, Ruilan Wang

Abstract

Background: Sepsis is still a common critical disease with high morbidity and mortality in intensive care unit. Despite published guidelines for sepsis, development of antibiotic therapy and advanced organ support technologies, the mortality of sepsis patients is still 25% or more. It is necessary to distinguish the subtypes of sepsis, and the targeted therapy for the patients need to be explored. Platelets have various biological functions in hemostasis and thrombosis, host defense, inflammatory/immune responses and tissue repair/regeneration. Moreover, severe thrombocytopenia or sustained thrombocytopenia was closely associated with multiply organ dysfunction and higher mortality in sepsis patients. The clinical therapies for thrombocytopenia are platelet transfusion and platelet-elevating drugs. However, platelet transfusion has many defects in clinical practice in sepsis patients, and the impact of platelet-elevating drugs for sepsis patients is still unclear. RESCUE trial is aim to explore the effect of a platelet-elevating drug, recombinant human thrombopoietin (rhTPO), as an effective rescue therapy on sepsis patients with acute severe thrombocytopenia.

Methods: It is a randomized, open-label, multi-center, controlled trial in 5 tertiary academic hospitals including medical, surgical or general ICUs. In this study, a total of 200 sepsis patients with severe thrombocytopenia will be randomly assigned in a 1:1 ratio to the control and rhTPO group. The patients will be followed up to 28 days after randomization. All patients in two groups receive the same treatment based on the guideline of Surviving Sepsis Campaign. Primary outcome is 28-day mortality. Secondary outcomes are the changes of PCs, blood transfusion, biomarkers of infection and organ function, days free from advanced organ support, drug-related adverse events, the length of ICU and hospital stay.

Discussion: RESCUE trial is the first randomized controlled trial to explore the impact of rhTPO for severe thrombocytopenia in sepsis patients diagnosed by sepsis-3.0 standard. Furthermore, RESCUE trial results will be of significant clinical value on the targeted therapy and add clinical evidence that rhTPO is an effective rescue therapy for these sepsis patients.

Trial registration: ClinicalTrials.gov : NCT02707497. Registered Date: March 3rd, 2016. Protocol Version 3. Protocol Date: January 25th, 2019.

Keywords: Mortality; Rescue therapy; Sepsis; Severe thrombocytopenia; Thrombopoietin.

Conflict of interest statement

RL. W declares that RhTPO in this study will be sponsored by Shenyang Sunshine Pharmaceutical Co., Ltd. And Shenyang Sunshine Pharmaceutical Co., Ltd. has no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of RESCUE trial procedure

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