Eltrombopag Plus rhTPO Versus Eltrombopag for ITP During the COVID-19 Pandemic (ELABORATE-19)

Study Overview
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Brief Summary
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This is a prospective, multicenter, randomized, open-label study to investigate the efficacy and safety of eltrombopag plus recombinant human thrombopoietin (rhTPO) versus eltrombopag as treatment for corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) during the COVID-19 pandemic.

Detailed Description
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During the COVID-19 pandemic, the classical subsequent treatment regimen for ITP of immunosuppressants and/or steroids might increase patients' susceptibility of virus infections. To minimize ITP patients' risk during the COVID-19 global crisis and to improve treatment efficacy, this treatment regimen of eltrombopag plus recombinant human thrombopoietin (rhTPO) should be investigated. Recombinant human thrombopoietin (rhTPO) is a full-length glycosylated-TPO produced by Chinese hamster ovary cells, which showed its effectiveness in ITP in a variety of studies. Eltrombopag, a small molecule agonist of thrombopoietin receptor (TPO-RA), was recommended as the subsequent treatment for ITP patients, which also already showed robust efficacy. Both eltrombopag and rhTPO demonstrated good safety in ITP patients. Since they increase the number of platelets through different mechanisms, and previous studies demonstrated that they might exert synergic effect. The investigators hypothesized that the combination of these two agents could be a promising option for ITP treatment. This study aimed to evaluate the sustained responses and safety of eltrombopag plus rhTPO as treatment for corticosteroid-resistant or relapsed ITP patients during the COVID-19 pandemic.

Official Title
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The Combination of Eltrombopag and Recombinant Human Thrombopoietin (rhTPO) Versus Eltrombopag Monotherapy as Subsequent Treatment for Immune Thrombocytopenia During the COVID-19 Pandemic

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Eltrombopag
* Drug: rhTPO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically confirmed corticosteroid-resistant or relapsed immune thrombocytopenic purpura (ITP) Platelet count less than 30×10^9/L on two occasions or Platelets above 30×10^9/L combined with bleeding manifestation (WHO bleeding scale 2 or above) Subject is ≥ 18 years Subject has signed and provided written informed consent. Fertile patients must use effective contraception during treatment and observational period Negative pregnancy test Exclusion Criteria: Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL Have an inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/or an aspartate aminotransaminase or alanine aminotransferase level > 3×upper limit of normal Have a New York Heart Classification III or IV heart disease Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures Have active hepatitis B or hepatitis C infection Have a HIV infection Have active infection requiring antibiotic therapy within 7 days prior to study entry Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug Previous splenectomy Had previous or concomitant malignant disease Not willing to participate in the study. Expected survival of < 2 years Intolerant to murine antibodies Immunosuppressive treatment within the last 2 weeks Connective tissue disease Autoimmune hemolytic anemia Patients currently involved in another clinical trial with evaluation of drug treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: eltrombopag plus rhTPO<br>Combination of eltrombopag and rhTPO | Drug: Eltrombopag<br>* Eltrombopag 25-75 mg oral daily according to platelet response.<br>* Other names: Revolade;Drug: rhTPO<br>* Rh-TPO 300U/kg subcutaneous injection once daily for 7 consecutive days, followed by a tapering dose in maintenance therapy.<br>* Other names: TPIAO, tebiao;|
| Active Comparator: eltrombopag<br>Eltrombopag monotherapy | Drug: Eltrombopag<br>* Eltrombopag 25-75 mg oral daily according to platelet response.<br>* Other names: Revolade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10^9/L. | 6 months | 
| Response | A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia. | 6 months | 
| No response | No response (NR) was defined as platelet count < 30 × 10^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart. | 6 months | 
| Relapses | A relapses was defined as platelet count falls below 30×10^9/L or bleeding accrues after achieving R or CR. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early response | Early response was defined as the attainment of a platelet count ≥ 30 × 10⁹ and at least a doubling of baseline platelet count at 1 week. | 7 days | 
| Initial response | Initial treatment was defined as the attainment of a platelet count ≥ 30 × 10⁹ and at least a doubling of baseline platelet count at 1 month. | 1 month | 
| Durable response | Durable response was defined as the attainment of a platelet count ≥ 30 × 10⁹ and at least a doubling of baseline platelet count at 6 months. | 6 months | 
| TOR (time to response) | The time to achieve platelet count ≥ 30×10^9/L and at least 2-fold increase of the baseline count and absence of bleeding since start of treatment. | 6 months | 
| DOR (duration of response) | The duration of achieve platelet count ≥ 30×10^9/L and at least 2-fold increase of the baseline count and absence of bleeding since start of treatment. | 6 months | 
| Treatments associated adverse events | All patients were assessed for safety every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | 6 months | 
| Reduction in bleeding symptoms | Changes of bleeding after treatment. Bleeding was defined in accordance with the WHO bleeding scale (0, no bleeding; 1, petechiae; 2, mild blood loss; 3, gross blood loss; and 4, debilitating blood loss). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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corticosteroid-resistant or relapsed ITP, eltrombopag, recombinant human thrombopoietin (rhTPO)