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

This study has been completed.
Information provided by (Responsible Party):
Shire Identifier:
First received: December 4, 2007
Last updated: October 15, 2015
Last verified: May 2014
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).

Thrombocythemia, Essential

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Shire:

Primary Outcome Measures:
  • Percentage of Participants With At Least One Pre-Defined Event (PDE), Deaths, Pregnancies [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Suspected Serious Adverse Reaction (SSAR) Events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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.

Secondary Outcome Measures:
  • Event Rate of Thrombohaemorrhagic Events [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Platelet Count [ Time Frame: Baseline, Month 6,12,18, 24, 30, 36, 42, 48, 54, 60 ] [ Designated as safety issue: No ]
  • Duration of Exposure for Each Essential Thrombocythemia (ET) Therapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Cumulative Dose for Each Essential Thrombocythemia (ET) Therapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Since the study is observational nature, interpreting the table is difficult due to inconsistencies in reporting the units of the dose.

Enrollment: 3647
Study Start Date: May 2005
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
XAGRID® (anagrelide hydrochloride)
Xagrid + Other cytoreductive
Other cytoreductive


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients receiving cytoreductive therapy for the treatment of at-risk essential thrombocytopenia (ET).

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00567502

  Show 164 Study Locations
Sponsors and Collaborators
Principal Investigator: Gunnar Birgegard, MD University Hospital, Uppsala, Sweden
  More Information

No publications provided by Shire

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Shire Identifier: NCT00567502     History of Changes
Other Study ID Numbers: SPD422-401
Study First Received: December 4, 2007
Results First Received: March 25, 2015
Last Updated: October 15, 2015
Health Authority: United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Thrombocythemia, Essential
Blood Coagulation Disorders
Blood Platelet Disorders
Bone Marrow Diseases
Hematologic Diseases
Hemorrhagic Disorders
Myeloproliferative Disorders
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Therapeutic Uses processed this record on November 27, 2015