Ignite Creation Date:
2024-05-06 @ 3:59 AM
Last Modification Date:
2024-10-26 @ 11:41 AM
Study NCT ID:
NCT02422394
Status:
COMPLETED
Last Update Posted:
2018-08-21
First Post:
2015-04-14
Brief Title:
Eltrombopag for Inherited Thrombocytopenias
Sponsor:
Fondazione IRCCS Policlinico San Matteo di Pavia
Organization:
Fondazione IRCCS Policlinico San Matteo di Pavia
Study Overview
Official Title:
Eltrombopag for Inherited Thrombocytopenias
Status:
COMPLETED
Status Verified Date:
2018-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Inherited thrombocytopenias ITs are a heterogeneous group of disorders characterized by a reduced number of blood platelets and a consequent bleeding tendency that ranges from mild to life-threatening Thrombocytopenia is caused by genetic mutations and therefore is present throughout life and can be transmitted to the progeny Some patients with severely reduced platelet count present spontaneous bleeding which represents a major clinical problem in fact bleeding diathesis exposes these subjects to the risk of severe hemorrhages affects their quality of life and often requires hospitalization andor transfusions Conversely other patients with ITs have absent or mild spontaneous bleeding tendency However even these patients are at risk of major bleeding on the occasion of surgery or other invasive procedures Therefore the potential for hemorrhages on the occasion of invasive procedures represent a clinical problem for all patients affected by ITs
Eltrombopag is a drug available in tablets which stimulates the production of platelets by the bone marrow A previous study demonstrated that a short course of eltrombopag was effective in increasing platelet count in most patients with the MYH9-related disease MYH9-RD the most frequent form of IT Eltrombopag was given for 3 to 6 weeks to 12 patients with MYH9-RD and platelet counts lower than 50 x10e9L Eleven patients responded to the drug and 8 of them obtained platelet counts higher than 100 x10e9L or three times the baseline value Remission of spontaneous bleeding was achieved by 8 of 10 patients and treatment was well tolerated in all the cases Based on these findings short-term eltrombopag courses have been successfully used for preparing for major surgery two patients with MYH9-RD and less than 20 x10e9 plateletsL
The present study has two main objectives - To verify if eltrombopag is effective in transiently increasing platelet count over 100 x 10e9L and abolishing bleeding tendency in patients with different forms of IT
To this end eltrombopag will be given for 3-6 weeks to patients with different forms of IT Eltrombopag will be administered at the dose of 50 mgday for 3 weeks After 3 weeks of treatment the patients who will obtain a platelet count higher than 100 x10e9L and complete remission of bleeding tendency will stop therapy In the other cases patients will be treated with eltrombopag at a higher dose 75 mgday for 3 additional weeks This treatment schedule is called Phase 1 of the study
If the study will achieve this goal short-term eltrombopag could be potentially used in the future to prepare these patients for surgery or other invasive procedures
- To verify if eltrombopag can be used to stably reduce spontaneous bleeding tendency for long periods of time in patients with clinically significant spontaneous hemorrhages
To this end patients with clinically significant spontaneous bleedings at baseline and who had their bleeding tendency reduced during the Phase 1 of the study without severe side effects will be admitted to the Phase 2 of the study
During the Phase 2 patients will be treated with eltrombopag for 16 weeks In order to determine the lowest dose of eltrombopag that is able to reduce or abolish their bleeding tendency patients will start treatment with eltrombopag 25 mgday for 4 weeks Then every 4 weeks patients will be re-evaluated and the dosage of eltrombopag will be adjusted according to bleeding tendency and platelet count The dosages of eltrombopag that can be used in the Phase 2 range from 125 to 75 mgday
Other objectives of the study are
to evaluate safety and tolerability of Eltrombopag in patients affected with ITs
to identify the dosages of Eltrombopag required for achieving the primary endpoints of Phases 1 and 2
to study the effects of Phase 2 treatment on patients health-related quality of life HR-QoL
to study the effects of treatment on some laboratory parameters related to platelet production and function
All patients will be undergo a follow-up visit 30 days after completion of treatment
Patients will be treated as outpatients The evaluation of patients at enrollment and at each subsequent on-treatment and post-treatment visits includes medical history physical examination evaluation of bleeding tendency according to WHO bleeding scale CBC and differential platelet count by phase-contrast microscopy peripheral blood smear examination plasma transaminases bilirubin and creatinine urine analysis ophthalmic assessment only at some visits measurement of serum thrombopoietin level evaluation of HR-QoL only at baseline and during Phase 2 evaluation of in vitro platelet aggregation in response to ADP collagen and ristocetin whenever platelet count is over 100 x 10e9L
Eltrombopag is a drug available in tablets which stimulates the production of platelets by the bone marrow A previous study demonstrated that a short course of eltrombopag was effective in increasing platelet count in most patients with the MYH9-related disease MYH9-RD the most frequent form of IT Eltrombopag was given for 3 to 6 weeks to 12 patients with MYH9-RD and platelet counts lower than 50 x10e9L Eleven patients responded to the drug and 8 of them obtained platelet counts higher than 100 x10e9L or three times the baseline value Remission of spontaneous bleeding was achieved by 8 of 10 patients and treatment was well tolerated in all the cases Based on these findings short-term eltrombopag courses have been successfully used for preparing for major surgery two patients with MYH9-RD and less than 20 x10e9 plateletsL
The present study has two main objectives - To verify if eltrombopag is effective in transiently increasing platelet count over 100 x 10e9L and abolishing bleeding tendency in patients with different forms of IT
To this end eltrombopag will be given for 3-6 weeks to patients with different forms of IT Eltrombopag will be administered at the dose of 50 mgday for 3 weeks After 3 weeks of treatment the patients who will obtain a platelet count higher than 100 x10e9L and complete remission of bleeding tendency will stop therapy In the other cases patients will be treated with eltrombopag at a higher dose 75 mgday for 3 additional weeks This treatment schedule is called Phase 1 of the study
If the study will achieve this goal short-term eltrombopag could be potentially used in the future to prepare these patients for surgery or other invasive procedures
- To verify if eltrombopag can be used to stably reduce spontaneous bleeding tendency for long periods of time in patients with clinically significant spontaneous hemorrhages
To this end patients with clinically significant spontaneous bleedings at baseline and who had their bleeding tendency reduced during the Phase 1 of the study without severe side effects will be admitted to the Phase 2 of the study
During the Phase 2 patients will be treated with eltrombopag for 16 weeks In order to determine the lowest dose of eltrombopag that is able to reduce or abolish their bleeding tendency patients will start treatment with eltrombopag 25 mgday for 4 weeks Then every 4 weeks patients will be re-evaluated and the dosage of eltrombopag will be adjusted according to bleeding tendency and platelet count The dosages of eltrombopag that can be used in the Phase 2 range from 125 to 75 mgday
Other objectives of the study are
to evaluate safety and tolerability of Eltrombopag in patients affected with ITs
to identify the dosages of Eltrombopag required for achieving the primary endpoints of Phases 1 and 2
to study the effects of Phase 2 treatment on patients health-related quality of life HR-QoL
to study the effects of treatment on some laboratory parameters related to platelet production and function
All patients will be undergo a follow-up visit 30 days after completion of treatment
Patients will be treated as outpatients The evaluation of patients at enrollment and at each subsequent on-treatment and post-treatment visits includes medical history physical examination evaluation of bleeding tendency according to WHO bleeding scale CBC and differential platelet count by phase-contrast microscopy peripheral blood smear examination plasma transaminases bilirubin and creatinine urine analysis ophthalmic assessment only at some visits measurement of serum thrombopoietin level evaluation of HR-QoL only at baseline and during Phase 2 evaluation of in vitro platelet aggregation in response to ADP collagen and ristocetin whenever platelet count is over 100 x 10e9L
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None