Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00175838
Status:
COMPLETED
Last Update Posted:
2017-01-18
First Post:
2005-09-09
Brief Title:
Primary Thrombocythaemia 1 Trial
Sponsor:
University of Cambridge
Organization:
University of Cambridge
Study Overview
Official Title:
A Randomised Trial to Compare Aspirin vs HydroxyureaAspirin in Intermediate Risk Primary Thrombocythaemia and Aspirin Only With Observation in Low RiskPrimary Thrombocythaemia
Status:
COMPLETED
Status Verified Date:
2017-01
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:
PT-1
Brief Summary:
The purpose of this trial is to see if Hydroxyurea aspirin is a better treatment than aspirin alone for Intermediate Risk Primary Thrombocythemia PT patients
Detailed Description:
The myeloproliferative disease primary thrombocythaemia PT has a median age of presentation of 60 years but is increasingly being recognised at an earlier age The risks of the untreated condition are micro-vascular and major vessel occlusive events and haemorrhage Older patients and those with a previous thrombosis are particularly prone to experience a significant vascular occlusive event An anti-aggregating agent such as aspirin has been shown to reducealleviate minor ischaemic symptoms Therefore except in patients with haemorrhagic symptoms peptic ulceration and known side-effects to aspirin the use of low-dose aspirin is appropriate
Myelofibrotic and acute leukaemic transformations can be long-term complications of PT The ability of therapeutic agents to delay myelofibrosis or reduceincrease the incidence of acute leukaemia in prospective studies is unknown However examination of retrospective data provides anxiety about the leukaemogenic risk of the commonly used cytoreductive agent hydroxyurea From an analysis of a few relatively small studies of primary thrombocythaemia the incidence of acute leukaemic transformation in selected patients treated with hydroxyurea has been given as 5-10 over 4-11 years 1
Based on the risk factors for vascular occlusion older patients with a thrombotic history and high platelet count can be separated into a high risk group There is evidence from a randomised prospective study of high-risk patients that cytoreduction with hydroxyurea significantly reduces vascular occlusion 2 The observed reduction in this prospective study of 29 months median duration was from 24 for those not given cytoreductive treatment to 36 for those receiving hydroxyurea - approximately a six-fold reduction In another prospective study where all patients received hydroxyurea an incidence of major thrombotic events was 56year 3 In these high-risk patients cytoreductive treatment should therefore be given The high risk arm of the PT1 trial which has now closed assessed the cytoreductive treatment of choice for these high risk patients and the results suggest that hydroxyurea plus aspirin is superior to anagrelide plus aspirin 4
In the patients at lower risk of vascular occlusion the dilemma is that the risk of vascular occlusion in untreated patients is relatively low but includes major life-threatening events In two small prospective studies of these patients not receiving platelet lowering agents the observed major complications were 3 and 41 per year and the total complications were 51 and 105 per year respectively 1 Cyto-reductive treatment should prevent such events and one could predict a similar reduction in complications as seen in the high-risk patients However there is evidence that in patients under the age of 40 years the complication rate is only one quarter of that seen in patients aged 40 - 59 years 5 Therefore it has been decided to divide these patients at lower risk of vascular occlusion into intermediate and low risk groups Patients aged 40-59 years will fall into the intermediate risk group and will be randomised to cytoreduction or not while all will receive aspirin Patients under 40 years will form the low-risk group and will receive aspirin alone Cyto-reductive treatment might also delay myelofibrotic transformation as observed in primary polycythaemia However this benefit and the possible reduction in vaso-occlusive episodes need to be balanced against the potential long-term risk of increasing acute leukaemic transformation
Myelofibrotic and acute leukaemic transformations can be long-term complications of PT The ability of therapeutic agents to delay myelofibrosis or reduceincrease the incidence of acute leukaemia in prospective studies is unknown However examination of retrospective data provides anxiety about the leukaemogenic risk of the commonly used cytoreductive agent hydroxyurea From an analysis of a few relatively small studies of primary thrombocythaemia the incidence of acute leukaemic transformation in selected patients treated with hydroxyurea has been given as 5-10 over 4-11 years 1
Based on the risk factors for vascular occlusion older patients with a thrombotic history and high platelet count can be separated into a high risk group There is evidence from a randomised prospective study of high-risk patients that cytoreduction with hydroxyurea significantly reduces vascular occlusion 2 The observed reduction in this prospective study of 29 months median duration was from 24 for those not given cytoreductive treatment to 36 for those receiving hydroxyurea - approximately a six-fold reduction In another prospective study where all patients received hydroxyurea an incidence of major thrombotic events was 56year 3 In these high-risk patients cytoreductive treatment should therefore be given The high risk arm of the PT1 trial which has now closed assessed the cytoreductive treatment of choice for these high risk patients and the results suggest that hydroxyurea plus aspirin is superior to anagrelide plus aspirin 4
In the patients at lower risk of vascular occlusion the dilemma is that the risk of vascular occlusion in untreated patients is relatively low but includes major life-threatening events In two small prospective studies of these patients not receiving platelet lowering agents the observed major complications were 3 and 41 per year and the total complications were 51 and 105 per year respectively 1 Cyto-reductive treatment should prevent such events and one could predict a similar reduction in complications as seen in the high-risk patients However there is evidence that in patients under the age of 40 years the complication rate is only one quarter of that seen in patients aged 40 - 59 years 5 Therefore it has been decided to divide these patients at lower risk of vascular occlusion into intermediate and low risk groups Patients aged 40-59 years will fall into the intermediate risk group and will be randomised to cytoreduction or not while all will receive aspirin Patients under 40 years will form the low-risk group and will receive aspirin alone Cyto-reductive treatment might also delay myelofibrotic transformation as observed in primary polycythaemia However this benefit and the possible reduction in vaso-occlusive episodes need to be balanced against the potential long-term risk of increasing acute leukaemic transformation
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| ISRCTN 72251782 | None | None | None |
| EUdraCT no2004-000245-38 | None | None | None |