Ignite Creation Date:
2024-05-06 @ 5:05 PM
Last Modification Date:
2024-10-26 @ 2:22 PM
Study NCT ID:
NCT05198960
Status:
RECRUITING
Last Update Posted:
2023-10-30
First Post:
2021-11-09
Brief Title:
AVAJAK ApixabanRivaroxaban Versus Aspirin for Primary Prevention of Thrombo-embolic Complications in JAK2V617F-positive Myeloproliferative Neoplasms
Sponsor:
University Hospital Brest
Organization:
University Hospital Brest
Study Overview
Official Title:
AVAJAK ApixabanRivaroxaban Versus Aspirin for Primary Prevention of Thrombo-embolic Complications in JAK2V617F-positive Myeloproliferative Neoplasms
Status:
RECRUITING
Status Verified Date:
2023-10
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:
AVAJAK
Brief Summary:
Philadelphia-negative myeloproliferative neoplasms MPN are frequent and chronic myeloid malignancies including Polycythemia Vera PV essential thrombocythemia ET Primary Myelofibrosis PMF and Prefibrotic myelofibrosis PreMF These MPNs are caused by the acquisition of mutations affecting activationproliferation pathways in hematopoietic stem cells The principal mutations are JAK2V617F calreticulin CALR exon 9 and MPL W515 ET or MFPPreMF patients who do not carry one of these three mutations are declared as triple-negative 3NEG cases even if they are real MPN cases
These diseases are at high risk of thrombo-embolic complications and with high morbiditymortality This risk varies from 4 to 30 depending on MPN subtype and mutational status
In terms of therapy all patients with MPNs should also take daily low-dose aspirin LDA as first antithrombotic drug which is particularly efficient to reduce arterial but not venous events
Despite the association of a cytoreductive drug and LDA thromboses still occur in 5-8 patientsyear
All these situations have been explored in biological or clinical assays All of them could increase the bleeding risk We should look at different ways to reduce the thrombotic incidence Direct Oral Anticoagulants DOAC In the general population in medical or surgical contexts DOACs have demonstrated their efficiency to prevent or cure most of the venous or arterial thrombotic events
At the present time DOAC can be used in cancer populations according to International Society on Thrombosis and Haemostasis ISTH recommendations except in patients with cancer at high bleeding risk gastro-intestinal or genito-urinary cancers Unfortunately in trials evaluating DOAC in cancer patients most patients have solid rather than hematologic cancers generally less than 10 of the patients mostly lymphoma or myeloma
In cancer patients DOAC are also highly efficient to reduce the incidence of thrombosis -30 to 60 but patients are exposed to a higher hemorrhagic risk especially in digestive cancer patients
In the cancer population pathophysiology of both thrombotic and hemorrhagic events may be quite different between solid cancers and MPN If MPN patients are also considered to be cancer patients in many countries the pathophysiology of thrombosis is quite specific hyperviscosity platelet abnormalities clonality specific cytokines and they are exposed to a lower risk of digestive hemorrhages It is thus difficult to extend findings from the general cancer population to MPN patients
Unfortunately only scarce retrospective data regarding the use of DOAC in MPNs are available data
We were the first to publish a real-life study about the use the impact and the risks in this population In this local retrospective study 25 patients with MPN were treated with DOAC for a median time of 21 years We observed only one thrombosis 4 and three major hemorrhages 12 after trauma or unprepared surgery Furthermore we have compared the benefitrisk balance compared to patients treated with LDA without difference
With the increasing evidences of efficacy and tolerance of DOAC in large cohorts of patients including cancer patients with their proven efficacy on prevention of both arterial and venous thrombotic events and because of the absence of prospective trial using these drugs in MPN patients we propose to study their potential benefit as primary thrombotic prevention in MPN
These diseases are at high risk of thrombo-embolic complications and with high morbiditymortality This risk varies from 4 to 30 depending on MPN subtype and mutational status
In terms of therapy all patients with MPNs should also take daily low-dose aspirin LDA as first antithrombotic drug which is particularly efficient to reduce arterial but not venous events
Despite the association of a cytoreductive drug and LDA thromboses still occur in 5-8 patientsyear
All these situations have been explored in biological or clinical assays All of them could increase the bleeding risk We should look at different ways to reduce the thrombotic incidence Direct Oral Anticoagulants DOAC In the general population in medical or surgical contexts DOACs have demonstrated their efficiency to prevent or cure most of the venous or arterial thrombotic events
At the present time DOAC can be used in cancer populations according to International Society on Thrombosis and Haemostasis ISTH recommendations except in patients with cancer at high bleeding risk gastro-intestinal or genito-urinary cancers Unfortunately in trials evaluating DOAC in cancer patients most patients have solid rather than hematologic cancers generally less than 10 of the patients mostly lymphoma or myeloma
In cancer patients DOAC are also highly efficient to reduce the incidence of thrombosis -30 to 60 but patients are exposed to a higher hemorrhagic risk especially in digestive cancer patients
In the cancer population pathophysiology of both thrombotic and hemorrhagic events may be quite different between solid cancers and MPN If MPN patients are also considered to be cancer patients in many countries the pathophysiology of thrombosis is quite specific hyperviscosity platelet abnormalities clonality specific cytokines and they are exposed to a lower risk of digestive hemorrhages It is thus difficult to extend findings from the general cancer population to MPN patients
Unfortunately only scarce retrospective data regarding the use of DOAC in MPNs are available data
We were the first to publish a real-life study about the use the impact and the risks in this population In this local retrospective study 25 patients with MPN were treated with DOAC for a median time of 21 years We observed only one thrombosis 4 and three major hemorrhages 12 after trauma or unprepared surgery Furthermore we have compared the benefitrisk balance compared to patients treated with LDA without difference
With the increasing evidences of efficacy and tolerance of DOAC in large cohorts of patients including cancer patients with their proven efficacy on prevention of both arterial and venous thrombotic events and because of the absence of prospective trial using these drugs in MPN patients we propose to study their potential benefit as primary thrombotic prevention in MPN
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None