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A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00202644
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : January 24, 2018
Last Update Posted : December 13, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

Tracking Information
First Submitted Date  ICMJE September 12, 2005
First Posted Date  ICMJE September 20, 2005
Results First Submitted Date  ICMJE October 13, 2016
Results First Posted Date  ICMJE January 24, 2018
Last Update Posted Date December 13, 2018
Actual Study Start Date  ICMJE January 13, 2006
Actual Primary Completion Date December 15, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
  • Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time [ Time Frame: Baseline and Month 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36 ]
    The LVEF was measured by echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function.
  • Platelet Count at Month 6 [ Time Frame: Month 6 ]
    Platelet count was evaluated.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
Cardiovascular safety as assessed by echocardiography at 3 years.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
  • Change From Baseline in Platelet Counts at Month 3 and 36 [ Time Frame: Baseline and Month 3 and 36 ]
    Platelet count was evaluated throughout the study.
  • Percentage of Participants With Complete Response [ Time Frame: Baseline up to Month 36 ]
    A complete response was defined as a platelet count of less than (<) 400x10^9/Liter which was confirmed over 2 consecutive visits at least 28 days apart.
  • Percentage of Participants With Partial Response [ Time Frame: Baseline up to Month 36 ]
    A partial response is defined as a platelet count of 400-600 x 10^9/Liter and a reduction in platelet count of at least 200 x 10^9/Liter from baseline which was confirmed over 2 consecutive visits at least 28 days apart.
  • Time to Complete Response [ Time Frame: Baseline up to Month 36 ]
    Time in days from the date of the first dose of study medication to the date of the first visit at which response was classified. If a participant did not achieve response then they were censored at their last visit in the study (Month 36 or withdrawal).
  • Time to Partial Response [ Time Frame: Baseline up to Month 36 ]
    Time in days from the date of the first dose of study medication to the date of the first visit at which response was classified. If a participant did not achieve response then they were censored at their last visit in the study (Month 36 or withdrawal).
  • Number of Participants With Thrombotic and Haemorrhagic Events [ Time Frame: From the signing of informed consent until the last study-related visit (Month 36) ]
    Thrombohaemorrhagic events are a well-known complication of the underlying essential thrombocythemia (ET) and disease progression. Events such as arterial and venous thrombosis, serious haemorrhage (including gastrointestinal haemorrhage), and death from vascular causes have been reported in participants who received cytoreductive treatment.
  • Change From Baseline in White Blood Cell Count Over Time [ Time Frame: Baseline and Month 6, 12, 18, 24, 30 and 36 ]
    White blood cell count was evaluated throughout the study.
  • Change From Baseline in Red Blood Cell Count Over Time [ Time Frame: Baseline and Month 6, 12, 18, 24, 30 and 36 ]
    Red blood cell count was evaluated throughout the study.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
  • Platelet counts
  • Cytoreductive impact on WBC and RBC lines
  • Tolerability
  • Incidence of disease related thrombotic and haemorrhagic events
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients
Official Title  ICMJE A Phase IIIb, Randomized, Open Label Study to Compare the Safety, Efficacy and Tolerability of Anagrelide Hydrochloride Versus Hydroxyurea in High-Risk Essential Thrombocythaemia Patients.
Brief Summary Essential thrombocythaemia is a disorder of bone marrow, which causes too many platelets to be produced. Platelets are small cells carried around in the blood, which help form blood clots. When patients have too many platelets, there is a risk of blood clots forming unnecessarily and excessive bleeding. The aim of this study is to gain additional information on the safety profile of Anagrelide (Xagrid(r)) and Hydroxyurea (also known as hydroxycarbamide).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Thrombocythemia, Hemorrhagic
Intervention  ICMJE
  • Drug: Anagrelide
    Anagrelide hydrochloride 0.5mg capsules;initial dose administered will be 1.0mg/day administered as 0.5mg bid. The dose will be titrated such that the total daily dose is incremented by no more than 0.5mg per week as required depending on platelet reduction versus adverse event profile.
  • Drug: Hydroxyurea
    Hydroxyurea is 500mg hydroxycarbamide capsules; initial dose is 1000mg/day, administered in two divided doses (500mg/dose). Dose titrated to effect to achieve a response.
Study Arms  ICMJE
  • Experimental: A
    Intervention: Drug: Anagrelide
  • Active Comparator: B
    Intervention: Drug: Hydroxyurea
Publications * Birgegård G, Folkvaljon F, Garmo H, Holmberg L, Besses C, Griesshammer M, Gugliotta L, Wu J, Achenbach H, Kiladjian JJ, Harrison CN. Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study. Leuk Res. 2018 Nov;74:105-109. doi: 10.1016/j.leukres.2018.10.006. Epub 2018 Oct 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 23, 2018)
150
Original Enrollment  ICMJE
 (submitted: September 14, 2005)
184
Actual Study Completion Date  ICMJE December 15, 2015
Actual Primary Completion Date December 15, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed diagnosis of essential thrombocythaemia - high risk profile
  • Previously untreated with a cytoreductive agent
  • Females of childbearing potential must have a negative urine pregnancy test prior to entering the study and must agree to use effective birth control for the duration of the study

Exclusion Criteria:

  • Diagnosis of any other myeloproliferative disorder
  • Any known cause for a secondary thrombocytosis
  • Anti-coagulant and anti-aggregant therapies
  • Known or suspected heart disease
  • Left Ventricular Ejection Fraction < 55%
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   France,   Hungary,   Poland,   Portugal,   Serbia
Removed Location Countries Belgium,   Croatia,   Czech Republic,   Ireland,   Italy,   Slovakia,   Slovenia,   Spain
 
Administrative Information
NCT Number  ICMJE NCT00202644
Other Study ID Numbers  ICMJE SPD422-403
2004-004061-15 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shire
Study Sponsor  ICMJE Shire
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Shire
PRS Account Shire
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP