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

NCT ID: NCT02707497

Last Updated: 2024-04-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2024-09-30

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.

Conditions

Sepsis; Thrombocytopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

rhTPO

Intervention Type: DRUG

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

placebo

The control group will not use any platelet-increased drugs.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The control group will not use any platelet-increased drugs.

Interventions

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

Intervention Type: DRUG

Placebo

The control group will not use any platelet-increased drugs.

Intervention Type: DRUG

Other Intervention Names

Recombinant Human TPO; No platelet-increased drug

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Huadong Hospital

OTHER

Sponsor Role: collaborator

Shanghai Tongji Hospital, Tongji University School of Medicine

OTHER

Sponsor Role: collaborator

Changhai Hospital

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

Shanghai University of Traditional Chinese Medicine

OTHER

Sponsor Role: collaborator

Fudan University

OTHER

Sponsor Role: collaborator

Ruilan Wang

OTHER

Sponsor Role: lead

Responsible Party

Ruilan Wang

The director of emergency and intensive care unit

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ruilan Wang, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

The department of ICU, Shanghai General Hospital, Shanghai Jiaotong University

Locations

Shanghai General Hospital, Shanghai Jiaotong University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ruilan Wang, MD,PhD

Role: CONTACT

wangyusun@hotmail.com

+86-13917138008

Facility Contacts

Ruilan Wang, MD

Role: primary

wangyusun@hotmail.com

+86-13917138008

References

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.

Reference Type: DERIVED

PMID: 31492102 (View on PubMed)

Other Identifiers

RWang-TPO-301

Identifier Type: -

Identifier Source: org_study_id