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)

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.

Treatment of severe thrombocytopenia associated with systemic lupus erythematosus in pregnancy with eltrombopag: A case report and literature review

“…However, some patients show a dependence on platelet transfusions and are insensitive to glucocorticoids, immunoglobulins or immunosuppressive drugs. For these patients, some experts attempted splenectomy, TPO analogue therapy, or intermittent plasma replacement 28,29 . However, splenectomy carries a high risk for patients in mid to late pregnancy, and the economic burden of plasma replacement is high, and platelet transfusions are difficult to maintain over the long term.…”

Clinically Useful and Cost-Effective of Recombinant Human Thrombopoietin in Treatment of Chemotherapy Induced Thrombocytopenia

“…Different degrees of thrombocytopenia caused by chemotherapy refers to the bone marrow suppression caused by chemical drugs [18,19]. Currently, rhTPO is a common clinical drug applicable for thrombocytopenia caused by chemotherapy; it has been con rmed to have superior clinical e cacy in increasing the platelet count [20]. rhTPO is currently the most vital hematopoietic growth factor found in the myeloid system, which is the most potent acting factor of megakaryocytes.…”

Platelets as a prognostic marker for sepsis

“…Platelets dysfunction was an independent risk factor for the prognosis of patients with sepsis has been confirmed by study, [ 12 , 13 ] but there is still a lack of large cohort studies and in the long-term prognosis of sepsis. This study is the first by a large clinical database to study the long-term prognosis of platelet dysfunction in patients with sepsis through the establishment of a nomogram.…”