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

The Effect of Recombinant Human Thrombopoietin(rhTPO) on Sepsis Patients With Acute Severe Thrombocytopenia：a Prospective, Multi-center, Open-label, ,Randomized, Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Thrombocytopenia
• Intervention / Treatment: Drug: rhTPO; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ruilan Wang, MD,PhD; Phone Number: +86-13917138008; Email: wangyusun@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Shanghai General Hospital, Shanghai Jiaotong University
      • Contact: Ruilan Wang, MD; Phone Number: +86-13917138008; Email: wangyusun@hotmail.com
      • Principal Investigator: Ruilan Wang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Recombinant Human TPO
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: No platelet-increased drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	The 28-day mortality of the patients	28 days after enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes of platelets counts (PCs) in the first 7 days	The changes of PCs in the first 7 days	7 days after enrolled
The clinical recovery time of PCs	The time of PCs that reach the standard of clinical recovery	28 days after enrolled
The amount of blood transfusion	The amount of blood transfusion (including platelets, RBC, FP)	28 days after enrolled
The proportion of blood transfusion	The proportion of patients who need blood transfusion(including platelets, RBC, FP)	28 days after enrolled
The changes of procalcitonin	The data of procalcitonin (PCT) in different time points	28 days after enrolled
The changes of C-reactive protein	The data of C-reactive protein (CRP) in different time points	28 days after enrolled
The changes of endotoxin	The data of endotoxin in different time points	28 days after enrolled
The changes of D-dimer and Fibrinogen	The data of D-dimer and Fibrinogen in different time points	28 days after enrolled
The changes of PT and APTT	The data of PT and APTT in different time points	28 days after enrolled
The changes of liver function	The data of the markers of liver function (including ALT, AST, TBIL, DBIL) in different time points	28 days after enrolled
The changes of renal function	The data of the markers of renal function (including serum Cr and BUN) in different time points	28 days after enrolled
The changes of cardiac function	The data of the markers of cardiac function (including Troponin I and BNP) in different time points	28 days after enrolled
The days free from advanced organ support	The days without advanced cardiovascular/respiratory/ renal support within 28 days	28 days after enrolled
The incidence of bleeding event	The incidence of bleeding event, according to Bleeding Academic Research Consortium Definition for Bleeding	28 days after enrolled
The incidences of drug-related adverse events	The incidences of drug-related adverse events as assessed by CTCAE v4.0	28 days after enrolled
The length of ICU and hospital stay	The days from enrolled to discharge from ICU or hospital	28 days after enrolled

Collaborators and Investigators

• Sponsor: Ruilan Wang
• Collaborators: Changhai Hospital; Shanghai Jiao Tong University School of Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai Tongji Hospital, Tongji University School of Medicine; Second Affiliated Hospital of Nanchang University; Huadong Hospital; Shanghai Fifth People's Hospital,Fudan University
• Investigators: Principal Investigator: Ruilan Wang, MD,PhD, The department of ICU, Shanghai General Hospital, Shanghai Jiaotong University

Publications and helpful links

General Publications

• Zhou Z, Feng T, Xie Y, Huang P, Xie H, Tian R, Qian B, Wang R. 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). BMC Infect Dis. 2019 Sep 6;19(1):780. doi: 10.1186/s12879-019-4388-2.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: March 3, 2016
• First Submitted That Met QC Criteria: March 11, 2016
• First Posted (Estimated): March 14, 2016

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: sepsis; platelets; recombinant human thrombopoietin; severe thrombocytopenia; 28-day mortality
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Blood Platelet Disorders; Cytopenia; Sepsis; Toxemia; Thrombocytopenia
• Other Study ID Numbers: RWang-TPO-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD, all IPD that underlie results in a publication.
• IPD Sharing Time Frame: starting 6 months after publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No