RESCUE: The Effect of REcombinant Human Thrombopoietin (rhTPO) on Sepsis Patients With aCUte Severe thrombocytopEnia
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether recombinant human thrombopoietin(rhTPO) can rapidly increase the platelets counts, shorten the time of the platelet returned to normal, reduce platelet transfusion and bleeding events, prompt recovery of organ function, decrease the length of ICU stay, and eventually reduce the 28-day mortality in sepsis patients with severe thrombocytopenia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
Sepsis is a high morbidity and mortality in critical care unit. Clinically, we found that secondary thrombocytopenia was common in the patients with sepsis, and the incidence can be as high as 55%. Moreover, many studies have shown that thrombocytopenia is an early prognostic marker in sepsis and an independent risk factor for the mortality of sepsis. Furthermore, sepsis patients with severe thrombocytopenia(PLT< 50×10^9/L) have the higher mortality of 50%-90%. And then, it has been reported that early recovery from thrombocytopenia helps to prevent the coagulopathy and decreases the mortality. Until now, the treatment of thrombocytopenia are mainly platelet transfusion and platelet-increased drugs. Because of source scarcity, transfusion-related infectious and immunological complications, platelet transfusion is limited in the clinical treatment. So, the use of platelet-increased drugs for replacement therapy becomes an inevitable trend. The primary purpose of this study is to explore the effect of platelet-increased drugs (rhTPO) on sepsis patients with severe thrombocytopenia.
The study is designed as a prospective, multi-center, open-label, randomized, controlled trial in 7 tertiary academic medical centers which are medical, surgical or general ICUs. Patient enrollment is expected to last up to 30 months. Eligible patients will be randomly assigned to the control and rhTPO add-on treatment in a dynamic random and competitive design in clinical trial sites. Sequential organ failure assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II) scores are as the dynamic equilibrium factors. Randomization will be done after the first assessment, ensuring that the assessing occupational therapist will not be biased at this time by knowing the group assignment. Both groups receive appropriate medical support and treatment based on guidelines issued by the surviving sepsis campaign.
The intervention group will receive rhTPO at a dose of 15000u/d, subcutaneous injection, for 7 consecutive days. It will be terminated when platelet counts (PCs) reach the standard of clinical recovery of platelets: increased by 50×109/L for 3 consecutive days compared with PCs at baseline, or PCs are more than 100×109/L, or the duration of rhTPO is more than 7 days. The time from randomization to administration of rhTPO will be within 24 hours. The control group will not use any platelet-increased drugs.
Platelet transfusion is advised to be administered when PCs are below 10×109/L in the absence of apparent bleeding; or below 20 ×109/L if the patient has a significant risk of bleeding in both two groups; or below 50 ×10^9/L if the patient has active bleeding or need invasive operation.
Patients will be followed for 28 days. PCs will be monitored every day until the first 7 days, followed by tests once a week. Liver and renal function, coagulation function, inflammatory biomarkers (CRP, PCT), and the severity of the disease (SOFA, APACHEǁ) will be monitored before treatment, followed by tests once a week. And then, the number of blood transfusion (including platelets), the length of ICU stay, days free from advanced cardiovascular/respiratory/renal support, bleeding events, and any adverse effects will be recorded after treatment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: rhTPO Recombinant Human Thrombopoietin，TPIAO®, Shenyang Sunshine Pharmaceutical Company Limited [SUNSHINE], Shenyang, China）， 15000u/d, qd, subcutaneous injection, daily for no more than 7 consecutive days |
Drug: rhTPO
Recombinant Human Thrombopoietin，TPIAO®, Shenyang Sunshine Pharmaceutical Company Limited [SUNSHINE], Shenyang, China）， 15000u/d, qd, subcutaneous injection, daily for no more than 7 consecutive days
Other Names:
|
| Placebo Comparator: placebo The control group will not use any platelet-increased drugs. |
Drug: Placebo
The control group will not use any platelet-increased drugs.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mortality [28 days after enrolled]
The 28-day mortality of the patients
Secondary Outcome Measures
- The changes of platelets counts (PCs) in the first 7 days [7 days after enrolled]
The changes of PCs in the first 7 days
- The clinical recovery time of PCs [28 days after enrolled]
The time of PCs that reach the standard of clinical recovery
- The amount of blood transfusion [28 days after enrolled]
The amount of blood transfusion (including platelets, RBC, FP)
- The proportion of blood transfusion [28 days after enrolled]
The proportion of patients who need blood transfusion(including platelets, RBC, FP)
- The changes of procalcitonin [28 days after enrolled]
The data of procalcitonin (PCT) in different time points
- The changes of C-reactive protein [28 days after enrolled]
The data of C-reactive protein (CRP) in different time points
- The changes of endotoxin [28 days after enrolled]
The data of endotoxin in different time points
- The changes of D-dimer and Fibrinogen [28 days after enrolled]
The data of D-dimer and Fibrinogen in different time points
- The changes of PT and APTT [28 days after enrolled]
The data of PT and APTT in different time points
- The changes of liver function [28 days after enrolled]
The data of the markers of liver function (including ALT, AST, TBIL, DBIL) in different time points
- The changes of renal function [28 days after enrolled]
The data of the markers of renal function (including serum Cr and BUN) in different time points
- The changes of cardiac function [28 days after enrolled]
The data of the markers of cardiac function (including Troponin I and BNP) in different time points
- The days free from advanced organ support [28 days after enrolled]
The days without advanced cardiovascular/respiratory/ renal support within 28 days
- The incidence of bleeding event [28 days after enrolled]
The incidence of bleeding event, according to Bleeding Academic Research Consortium Definition for Bleeding
- The incidences of drug-related adverse events [28 days after enrolled]
The incidences of drug-related adverse events as assessed by CTCAE v4.0
- The length of ICU and hospital stay [28 days after enrolled]
The days from enrolled to discharge from ICU or hospital
Eligibility Criteria
Criteria
Inclusion Criteria:
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Confirmed or clinical diagnosed infection
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The change of Sequential Organ Failure Assessment(ΔSOFA) score ≥ 2
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PLT< 50×10^9/L
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Informed consent
Exclusion Criteria:
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History of the treatments with chemotherapeutic drugs or heparin within six months
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History of bone marrow stem cell disorders, malignancy, or immunologic diseases
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History of bone marrow, lung, liver, kidney, pancreas, or small bowel transplantation.
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Confirmed End-stage renal failure(GFR <10ml/min，Scr>707μmol/L)
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Confirmed Disseminated Intravascular Coagulation(DIC)
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Confirmed Hemorrhagic brain injury or need craniocerebral operation
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Died anticipated within 24 hours
-
Known pregnancy or at breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shanghai General Hospital, Shanghai Jiaotong University | Shanghai | Shanghai | China | 200080 |
Sponsors and Collaborators
- Ruilan Wang
- Huadong Hospital
- Shanghai Tongji Hospital, Tongji University School of Medicine
- Changhai Hospital
- Second Affiliated Hospital of Nanchang University
- Shanghai Jiao Tong University School of Medicine
- Shanghai University of Traditional Chinese Medicine
- Shanghai Fifth People's Hospital,Fudan University
Investigators
- Principal Investigator: Ruilan Wang, MD,PhD, The department of ICU, Shanghai General Hospital, Shanghai Jiaotong University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RWang-TPO-301