The Effect of REcombinant Human Thrombopoietin (rhTPO) on Sepsis Patients With aCUte Severe thrombocytopEnia

Phase 2

Recruiting

• Conditions: Sepsis; Thrombocytopenia
• Interventions: Drug: Placebo; Drug: rhTPO

• Registration Number: NCT02707497
• Lead Sponsor: Ruilan Wang

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.

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 50×10\^9/L for 3 consecutive days compared with PCs at baseline, or PCs are more than 100×10\^9/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 10×10\^9/L in the absence of apparent bleeding; or below 20 ×10\^9/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 Timeline

• Study First Submitted: 2016-03-03
• Study First Submitted QC: 2016-03-11
• Study First Posted: 2016-03-14
• Study Start: 2019-04-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-16
• Last Update Posted: 2024-04-18
• Primary Completion: 2024-08-31
• Study Completion: 2024-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Confirmed or clinical diagnosed infection
2. The change of Sequential Organ Failure Assessment(ΔSOFA) score ≥ 2
3. PLT< 50×10^9/L
4. Informed consent

Exclusion Criteria

1. History of the treatments with chemotherapeutic drugs or heparin within six months
2. History of bone marrow stem cell disorders, malignancy, or immunologic diseases
3. History of bone marrow, lung, liver, kidney, pancreas, or small bowel transplantation.
4. Confirmed End-stage renal failure(GFR <10ml/min，Scr>707μmol/L)
5. Confirmed Disseminated Intravascular Coagulation(DIC)
6. Confirmed Hemorrhagic brain injury or need craniocerebral operation
7. Died anticipated within 24 hours
8. Known pregnancy or at breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	The control group will not use any platelet-increased drugs.
rhTPO	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

Primary Outcome Measures

Name	Time	Method
Mortality	28 days after enrolled	The 28-day mortality of the patients

Secondary Outcome Measures

Name	Time	Method
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 proportion of blood transfusion	28 days after enrolled	The proportion of patients who need blood transfusion(including platelets, RBC, FP)
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 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
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 incidence of bleeding event	28 days after enrolled	The incidence of bleeding event, according to Bleeding Academic Research Consortium Definition for Bleeding
The clinical recovery time of PCs	28 days after enrolled	The time of PCs that reach the standard of clinical recovery
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 amount of blood transfusion	28 days after enrolled	The amount of blood transfusion (including platelets, RBC, FP)

Trial Locations

Locations (1)

Shanghai General Hospital, Shanghai Jiaotong University; 🇨🇳 Shanghai, Shanghai, China