Study to Identify and Describe Predictive Factors for Thromboembolic Events in Patients With High-risk Polycythemia Vera
- Conditions
- Polycythemia Vera
- Interventions
- Other: RuxolitinibOther: Hydroxyurea
- Registration Number
- NCT05548062
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This is a prospective observational study that will enroll patients with high-risk Polycythemia Vera (PV) with at least one Thromboembolic Event (TE) after diagnosis or up to 2 years prior to diagnosis.
This is a non-randomized study, and to ensure a sufficient number of patients in both cohorts, enrollment in each cohort will be terminated once the target of 150 patients has been reached.
- Detailed Description
All patients are already on treatment with hydroxyurea or ruxolitinib at enrollment as per clinical practice and independently of their participation in this study. In addition, the follow-up visits and the evaluation procedures required in the study protocol correspond to current clinical practice. According to local regulations related to observational studies, assessments such as blood tests are justified by the purpose and rationale of the study (i.e., the identification of possible predictive factors of TEs) and are considered current clinical practice. Data related to other procedures will be collected only if such procedures are performed as per clinical practice but are not required otherwise.
Patients in both cohorts will be followed for 3 years after enrollment and will have visits at Months 6, 12, 18, 24, 30 and 36. A time window of ± 1 month is permitted for all visits.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 242
- Signed informed consent must be obtained prior to participation in the study.
- Age ≥18 years.
- Diagnosis of PV according to WHO 2008 or WHO 2016 and high-risk stratification according to European LeukemiaNet (ELN) classification.
- At least one TE after diagnosis or up to 2 years prior to diagnosis.
- Patients on treatment with hydroxyurea at enrollment and for at least 18 months prior to enrollment or those on treatment with ruxolitinib who started treatment up to 18 months before enrollment.
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Ruxolitinib Ruxolitinib Patients on treatment with ruxolitinib who started treatment up to 18 months prior to enrollment. Hydroxyurea Hydroxyurea Patients being treated with hydroxyurea at enrollment and for at least 18 months prior to enrollment. Patients may switch to ruxolitinib treatment during the study in case of inadequate response or intolerance.
- Primary Outcome Measures
Name Time Method Number of patients with abnormal Body Mass Index (BMI) Up to month 36 Number of patients with abnormal Body Mass Index (BMI) will be collected
Blood pressure Up to month 36 Blood pressure is going to be collected
Number of patients with abnormal weight Up to month 36 Number of patients with abnormal weight will be collected
Number of patients with abnormal Neutrophil (NEP) count Up to 36 months Number of patients with abnormal Neutrophil (NEP) count will be collected
Percentage of abnormalities presented in patients with Thromboembolic Events (TEs) during the follow up Up to 36 months Demographics, blood pressure, laboratory blood tests, and use of antiplatelets and/or anticoagulants are predictors of TE occurrence, a univariate Cox regression model for repeated events will be applied for each predictor considering all the TEs occurring within 12 months and the time from baseline to each occurrence. Predictors found statistically significant at the 5% level will then be considered in a multivariate Cox regression model for repeated events.
Number of participants using antiplatelets and/or anticoagulants on the incidence of TEs Up to 36 months Number of participants using antiplatelets and/or anticoagulants on the incidence of Thromboembolic Events (TEs) will be collected
Number of patients with abnormal White blood Count (WBC) Up to 36 months Number of patients with abnormal White blood Count (WBC) will be collected
Number of patients with abnormal Lymphocytes (LYP) count Up to 36 months Number of patients with abnormal Lymphocytes (LYP) count will be collected
- Secondary Outcome Measures
Name Time Method Yearly incidence of TEs 36 months Yearly incidence of Thromboembolic Events (TEs) will be collected
Incidence of arterial and venous TEs in the hydroxyurea and ruxolitinib cohorts 36 months Incidence of arterial and venous TEs in the hydroxyurea and ruxolitinib cohorts will be collected
Incidence and severity of adverse events 36 months Incidence and severity of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Synergistic combinations of predictive factors Up to 36 months Synergistic combinations of predictive factors (Red cell Distribution Width, neutrophils, lymphocytes, neutrophil/ lymphocyte ratio and platelets).
Synergy score is defined as the product of the individual significances of variable 1 and 2 (expected) divided by the significance of the two-variable model (observed) To investigate cases of extreme synergy, instances in which two variables split the given cohort into high-risk and low-risk patients are far better than either variable alone. A simple synergy scoring metric to rank variable in terms of synergy (S):S12=(P1\*P2)/P12 where P1 and P2 are the maximum possible (Cox regression derived) p-values for variable 1 and variable 2 and P12 was the max. p-value possible from the combination of variables 1 and 1. This synergy is intended to capture a variable that may provide exclusive non-redundant information when attempting to split a cohort based on risk and may provide an added insight into the functional/clinical rationale of a model
Trial Locations
- Locations (1)
Novartis Investigative Site
🇮🇹Napoli, Italy