Safety and Pregnancy Outcomes in Thrombocythemia Patients Exposed to XAGRID® (Anagrelide Hydrochloride) Compared to Other Treatments

Study Overview
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Brief Summary
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This is an observational safety study being conducted in Europe comparing patients taking Xagrid to patients taking other cytoreductive treatments. The plan is to enrol at least 750 subjects taking Xagrid with up to 3000 subjects taking other cytoreductive therapies. The study will collect follow up data for 5 years for each patient enrolled that will focus on collecting data related to pre-defined events (PDEs) and Suspected Serious Adverse Reactions (SSARs).

Official Title
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A Non-Interventional, Post Authorisation Safety Study, to Continuously Monitor Safety and Pregnancy Outcomes in a Cohort of At-Risk Essential Thrombocythaemia (ET) Subjects Exposed to Xagrid Compared to Other Conventional Cytoreductive Treatments

Conditions
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Thrombocythemia, Essential

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High risk ET patients Subjects who can give written informed consent. Subjects taking cytoreductive therapy Exclusion Criteria: Contraindications listed by the product being used. Patient cannot be participating in another clinical trial.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>XAGRID® (anagrelide hydrochloride) | |
| 2<br>Xagrid + Other cytoreductive | |
| 3<br>Other cytoreductive | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies | Pre-defined events (PDEs) were evaluated whenever an event occurred and was defined by a panel of independent qualified physicians, blinded to cytoreductive therapy, validated all PDEs prior to analysis (Event Validation Panel). Non-PDE death only included deaths not recorded as outcome of another PDE. | Up to 5 years | 
| Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events | SSAR: serious adverse event (SAE) that was considered related to cytoreductive therapy. SAE: any untoward medical occurrence that at any dose resulted in death, life-threatening (at the time of the event), in-patient hospitalization/prolongation of existing hospitalization (elective hospitalizations/procedures for pre-existing conditions that had not worsened were excluded), resulted in persistent or significant disability/incapacity or congenital abnormality/birth defect. Relatedness (suspected/not suspected) to XAGRID or other cytoreductive theraphy was determined by the investigator. As for SSARs, it was important to consider whether the events were related to XAGRID or other cytoreductive therapy. A participant was included in Xagrid or other treatment group based on treatment exposure, participants received Xagrid + Other was counted both in Xagrid and other treatment group. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Rate of Thrombohaemorrhagic Events | Event Rate of Thrombohaemorrhagic Events was calculated by dividing number of participants with events by total patient-year exposure. The reporting unit is per 100 participant-years of treatment exposure. Thrombohaemorrhagic Events is a composite endpoint of the PDEs myocardial infarction, angina, stroke, transient ischaemic attack, venous thromboembolic events, intermittent claudication/digital ischaemia, and major haemorrhagic events. | Up to 5 years | 
| Platelet Count |  | Baseline, Month 6,12,18, 24, 30, 36, 42, 48, 54, 60 | 
| Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy | Total duration for each participant = sum of [stop date - start date + 1] across all periods of time where the specific treatment was taken during the study, where start date = registration/consent date for treatments started before registration/consent date and/or stop date withdrawal/final date for treatments ongoing at the time of withdrawal/end of study. Where a participant has multiple records of the same therapy on the same day, the therapy is counted once for that day. | Up to 5 years | 
| Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy | Since the study is observational nature, interpreting the table is difficult due to inconsistencies in reporting the units of the dose. | Up to 5 years |