A Study of Eltrombopag and Recombinant Human Thrombopoietin In Primary Immune Thrombocytopenia

Corticosteroid-resistant or Relapsed ITP Clinical Trial

Official title:

A Prospective Observational Study of Switching Eltrombopag and Recombinant Human Thrombopoietin In Primary Immune Thrombocytopenia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04214951
• Other study ID #: ZXH-ITP2019
• Status: Active, not recruiting
• Start date: January 1, 2020
• Est. completion date: December 2022

Study information

• Verified date: October 2020
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Thrombopoietin Receptor Agonists (TPO-ra) are novel treatments for patients with refractory Primary Immune Thrombocytopenia (ITP). Rh-TPO and eltrombopag increase the number of platelets through different mechanism. If there is cross-resistance between 2 drugs for the treatment of adult ITP is still no answer. The purpose of this study is to investigate the efficacy and safety of switching eltrombopag and Rh-TPO in adults with ITP.

Description:

Non-interventional study. Patients who fail previous steroids and receive rh-TPO and then switch to EPAG or vice versa will be enrolled. The reason for switch will be recorded. Patients in the rh-TPO group were given rh-TPO 300 U/kg once daily for 21 days, and those in the eltrombopag group were given eltrombopag 50mg once daily for 6 weeks. Rh-TPO and eltrombopag were terminated any time the platelet counts increased above 100 × 10^9/L in the rh-TPO group and 300 × 10^9/L in the eltrombopag group. The efficacy, safety, and patient/physician preference will be assessed and compared between the two agents.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2022
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1.18 years or older

2.Primary ITP

3.Platelet count = 30 × 109/l

4.Normal neutrophils, reticulocyte count, creatinine and liver enzyme values

5.Available follow-up of 2 months at least for each period

6.Failed initial glucocorticosteroid treatment

7.Unwillingness to accept splenectomy or failed splenectomy

-

Exclusion Criteria:

1. HIV, hepatitis B or C, Helicobacter pylori infection

2. Malignancy

3. Congenital or acquired immunologic deficit

4. History of thrombosis plus two or more risk factors

5. Nursing or pregnant women

6. Abnormal liver and renal functions: AST/ALT/total bilirubin =1.5 × ULN, creatinine =1.5 mg/dl

7. Severe heart and lung dysfunctions -

Related Conditions & MeSH terms

• Corticosteroid-resistant or Relapsed ITP
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Eltrombopag
Patients will be given eltrombopag 50mg once daily for 6 weeks.
• Recombinant human thrombopoietin (rh-TPO)
Patients will be given rh-TPO 300 U/kg once daily for 21 days.

Locations

Country	Name	City	State
China	Peking University Institute of Hematology	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (12)

Bussel JB, Lakkaraja M. Thrombopoietic agents: there is still much to learn. Presse Med. 2014 Apr;43(4 Pt 2):e69-78. doi: 10.1016/j.lpm.2014.02.008. Epub 2014 Mar 27. Review. — View Citation

Cantoni S, Carpenedo M, Mazzucconi MG, De Stefano V, Carrai V, Ruggeri M, Specchia G, Vianelli N, Pane F, Consoli U, Artoni A, Zaja F, D'adda M, Visentin A, Ferrara F, Barcellini W, Caramazza D, Baldacci E, Rossi E, Ricco A, Ciminello A, Rodeghiero F, Nichelatti M, Cairoli R. Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers. Am J Hematol. 2018 Jan;93(1):58-64. doi: 10.1002/ajh.24935. Epub 2017 Nov 9. — View Citation

Deutsch VR, Tomer A. Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside. Br J Haematol. 2013 Jun;161(6):778-93. doi: 10.1111/bjh.12328. Epub 2013 Apr 18. Review. — View Citation

Erhardt JA, Erickson-Miller CL, Aivado M, Abboud M, Pillarisetti K, Toomey JR. Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function. Exp Hematol. 2009 Sep;37(9):1030-7. doi: 10.1016/j.exphem.2009.06.011. Epub 2009 Jul 24. — View Citation

Erickson-Miller CL, Delorme E, Tian SS, Hopson CB, Landis AJ, Valoret EI, Sellers TS, Rosen J, Miller SG, Luengo JI, Duffy KJ, Jenkins JM. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009 Feb;27(2):424-30. doi: 10.1634/stemcells.2008-0366. — View Citation

Ghanima W, Godeau B, Cines DB, Bussel JB. How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment. Blood. 2012 Aug 2;120(5):960-9. doi: 10.1182/blood-2011-12-309153. Epub 2012 Jun 26. Review. — View Citation

González-Porras JR, Godeau B, Carpenedo M. Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia. Ther Adv Hematol. 2019 May 9;10:2040620719837906. doi: 10.1177/2040620719837906. eCollection 2019. Review. — View Citation

Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013 Jul;98(1):10-23. doi: 10.1007/s12185-013-1382-0. Epub 2013 Jul 3. Review. — View Citation

Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011 Apr 21;117(16):4190-207. doi: 10.1182/blood-2010-08-302984. Epub 2011 Feb 16. Review. — View Citation

Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010 Jan 14;115(2):168-86. doi: 10.1182/blood-2009-06-225565. Epub 2009 Oct 21. Review. — View Citation

Wang S, Yang R, Zou P, Hou M, Wu D, Shen Z, Lu X, Li Y, Chen X, Niu T, Sun H, Yu L, Wang Z, Zhang Y, Chang N, Zhang G, Zhao Y. A multicenter randomized controlled trial of recombinant human thrombopoietin treatment in patients with primary immune thrombocytopenia. Int J Hematol. 2012 Aug;96(2):222-8. doi: 10.1007/s12185-012-1124-8. Epub 2012 Jun 30. — View Citation

Wörmann B. Clinical indications for thrombopoietin and thrombopoietin-receptor agonists. Transfus Med Hemother. 2013 Oct;40(5):319-25. doi: 10.1159/000355006. Epub 2013 Sep 11. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate at 6 Weeks After Switching	The percentage of patients who have reached platelet count = 50×10^9/L at 6 weeks after switching.	6 weeks
Secondary	Treatments Associated Adverse Events	Adverse event/serious adverse event associated with study drugs during 6 weeks after switching	6 weeks
Secondary	Reasons of Switching	Reasons of switching eltrombopag and rh-TPO will be recorded, including lack of efficacy, patient preference, side effects, platelet count fluctuation	6 weeks
Secondary	Number of Participants With Bleeding Events	Number of participants with bleeding events of the two groups during 6 weeks after switching	6 weeks
Secondary	TOR (Time to Response)	The time to achieve platelet count = 50×10^9/L after switching.	6 weeks
Secondary	DOR (Duration of Response)	The duration of achieving platelet count = 50×10^9/L after switching.	6 weeks