Viewing Study NCT01645124



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Last Modification Date: 2024-10-26 @ 10:54 AM
Study NCT ID: NCT01645124
Status: TERMINATED
Last Update Posted: 2012-07-20
First Post: 2012-07-17

Brief Title: Large-scale Trial Testing the Intensity of CYTOreductive Therapy in Polycythemia Vera PV
Sponsor: Consorzio Mario Negri Sud
Organization: Consorzio Mario Negri Sud

Study Overview

Official Title: A Large-scale Trial Testing the Intensity of CYTOreductive Therapy to Prevent Cardiovascular Events In Patients With Polycythemia Vera PV
Status: TERMINATED
Status Verified Date: 2012-05
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Low accrual rate not allowing planned sample size leads to a futility condition
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: CYTO-PV
Brief Summary: CYTO-PV is a phase III Prospective Randomized Open-label with Blinded Endpoint evaluation PROBE multi-center clinical trial in patients with diagnosis of Polycythemia vera PV treated at the best of recommended therapies egadequate control of standard cardiovascular risk factors Irrespective of randomized interventions all patients will be administered low-dose aspirin when not contraindicated iethe standard antithrombotic treatment in PV patients

The purpose of this study to demonstrate that a more intensive cytoreductive therapy plus low-dose aspirin when not contraindicated with phlebotomy andor hydroxyurea HU aimed at maintaining hematocrit HCT 45 is more effective than a less intensive cytoreduction either with phlebotomy or HU plus low-dose aspirin when not contraindicated maintaining HCT in the range of 45-50 in the reduction of CV deaths plus thrombotic events stroke acute coronary syndrome ACS transient ischemic attack TIA pulmonary embolism PE splanchnic thrombosis deep vein thrombosis DVT and any other clinically relevant thrombotic event in patients with Polycythemia Vera treated at the best of recommended therapies eg adequate control of standard cardiovascular risk factors
Detailed Description: Polycythemia vera PV is a chronic myeloproliferative disorder characterized by clonal proliferation of hematopoietic progenitors resulting in expansion of the erythrocyte mass and its clinical course is affected by cardiovascular events the main cause of morbidity and mortality Arterial thrombotic events are predominant particularly large vessel arterial events including cerebrovascular accidents myocardial infarction and peripheral arterial occlusion Based on the complex relationship between thrombosis hematocrit and parameters of tissue perfusion and blood viscosity the latter has been proved to be an exponential function of the hematocrit Red cell aggregation increases at high hematocrit HCT levels creating the potential for vascular stasis As a result enhanced interplay between platelet leukocytes and vessel wall increases the risk of thrombosis

Considering the lack of effective therapeutic strategy targeted at the mutated allele JAK2V617F there is no known treatment that eradicates the abnormal clone apart from anecdotal cases of bone marrow transplantation Cytoreductive treatment by phlebotomy or chemotherapy however has dramatically reduced the number of thrombotic complications and substantially improved survival and today there is agreement that the goal of cytoreductive treatment should be to keep the HCT value below 045 in all PV patients

This was suggested on the basis of a small retrospective study of PV that more than 30 years ago showed a progressive increase in the incidence of vascular occlusive episodes at HCT levels higher than 44 and in patients treated according to the drugs and the therapeutic tenets of the time However no clinical trial has confirmed such findings The results of the two largest prospective studies currently available namely PVSG-1 and ECLAP suggest no difference in the risk of thrombosis among patients kept at HCT below 50

An association between relevant outcome events namely thrombotic events mortality and haematological progression and HCT in the evaluable range of 40-55 was found in the ECLAP population neither in the multivariate analysis at baseline nor in the time-dependent multivariate analysis The ECLAP trial demonstrated the antithrombotic efficacy of low-dose aspirin in this setting and the use of this therapy in clinical practice is likely to decrease meaningfully though not eliminate the high risk of thrombosis of PV patients

In conclusion the high incidence of thrombotic events irrespective of low-dose aspirin administration as well as of haematological transformation in the long term which have been shown in PV patients study suggest the need to investigate in depth the benefitrisk profile of current therapeutic options for cytoreductive therapy CYTO-PV is aimed at assessing the benefit risk profile of cytoreductive therapy with phlebotomy andor HU aimed at maintaining HCT 45 Vs maintaining HCT in the range 45-50 It is an independent investigator-generated pragmatic trial with broad selection criteria to mimic clinical practice in order to strengthen the transferability of its results to the population of PV patients it has been designed to be conducted without need of special facilities in the framework of the Italian Group of hematologic Adult diseases GIMEMA The optimization of therapeutic management of PV patients will allow to improve the prognosis of PV patients the allocation of the resources the Italian National Health Service IHS and the knowledge about the benefitrisk profile of pharmacological cytoreduction in PV

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