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

Phase 2
Conditions
Immune Thrombocytopenia
Interventions
Registration Number
NCT04516837
Lead Sponsor
Peking University People's Hospital
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
120
Inclusion Criteria
  1. Clinically confirmed corticosteroid-resistant or relapsed immune thrombocytopenic purpura (ITP)
  2. 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)
  3. Subject is ≥ 18 years
  4. Subject has signed and provided written informed consent.
  5. Fertile patients must use effective contraception during treatment and observational period
  6. Negative pregnancy test
Exclusion Criteria
  1. Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL
  2. 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
  3. Have a New York Heart Classification III or IV heart disease
  4. Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures
  5. Have active hepatitis B or hepatitis C infection
  6. Have a HIV infection
  7. Have active infection requiring antibiotic therapy within 7 days prior to study entry
  8. Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug
  9. Previous splenectomy
  10. Had previous or concomitant malignant disease
  11. Not willing to participate in the study.
  12. Expected survival of < 2 years
  13. Intolerant to murine antibodies
  14. Immunosuppressive treatment within the last 2 weeks
  15. Connective tissue disease
  16. Autoimmune hemolytic anemia
  17. Patients currently involved in another clinical trial with evaluation of drug treatment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
eltrombopag plus rhTPOEltrombopagCombination of eltrombopag and rhTPO
eltrombopag plus rhTPOrhTPOCombination of eltrombopag and rhTPO
eltrombopagEltrombopagEltrombopag monotherapy
Primary Outcome Measures
NameTimeMethod
No response6 months

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.

Complete response6 months

A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10\^9/L.

Response6 months

A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10\^9/L without recurrence of thrombocytopenia.

Relapses6 months

A relapses was defined as platelet count falls below 30×10\^9/L or bleeding accrues after achieving R or CR.

Secondary Outcome Measures
NameTimeMethod
DOR (duration of response)6 months

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.

Initial response1 month

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.

TOR (time to response)6 months

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.

Treatments associated adverse events6 months

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.

Early response7 days

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.

Durable response6 months

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.

Reduction in bleeding symptoms6 months

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).

Trial Locations

Locations (1)

Peking University Insititute of Hematology, Peking University People's Hospital

🇨🇳

Beijing, Beijing, China

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