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

• ClinicalTrials.gov Identifier: NCT04516837
• Recruitment Status: Unknown
• First Posted: August 18, 2020
• Last Update Posted: September 1, 2020
• Sponsor: Peking University People's Hospital
• Information provided by (Responsible Party): Xiao Hui Zhang, Peking University People's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Immune Thrombocytopenia	Drug: Eltrombopag; Drug: rhTPO	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Combination of Eltrombopag and Recombinant Human Thrombopoietin (rhTPO) Versus Eltrombopag Monotherapy as Subsequent Treatment for Immune Thrombocytopenia During the COVID-19 Pandemic
• Actual Study Start Date: August 31, 2020
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: August 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Complete response [ Time Frame: 6 months ]
   A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10^9/L.
2. Response [ Time Frame: 6 months ]
   A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia.
3. No response [ Time Frame: 6 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.
4. Relapses [ Time Frame: 6 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 :

1. Early response [ Time Frame: 7 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.
2. Initial response [ Time Frame: 1 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.
3. Durable response [ Time Frame: 6 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.
4. TOR (time to response) [ Time Frame: 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.
5. DOR (duration of response) [ Time Frame: 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.
6. Treatments associated adverse events [ Time Frame: 6 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.
7. Reduction in bleeding symptoms [ Time Frame: 6 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Xiaohui Zhang, MD; +86-13522338836; zhangxh100@sina.com

Contact: Xuelin Dou, MD; +86-15510491556; dxldw@163.com

Locations

China, Beijing

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

Beijing, Beijing, China, 100010

Contact: Xiaohui Zhang zhangxh100@sina.com

Sponsors and Collaborators

Peking University People's Hospital

Investigators

• Principal Investigator: Xiaohui Zhang, MD; Peking University People's Hospital, Peking University Insititute of Hematology

More Information

• Responsible Party: Xiao Hui Zhang, Vice president of Peking Univeristy Institute of Hematology, Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT04516837
• Other Study ID Numbers: ITP-PKU020
• First Posted: August 18, 2020
• Last Update Posted: September 1, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Xiao Hui Zhang, Peking University People's Hospital:

corticosteroid-resistant or relapsed ITP; eltrombopag; recombinant human thrombopoietin (rhTPO)

Additional relevant MeSH terms:

COVID-19; Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders; Hematologic Diseases; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Skin Manifestations