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

Primary Purpose

Thrombocythemia, Hemorrhagic

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Anagrelide
Hydroxyurea
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thrombocythemia, Hemorrhagic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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%

Sites / Locations

  • University Multiprofile Hospital for Active Treatment ''Dr Georgi Stranski'' - Pleven
  • University Multiprofile Hospital for active Treatment ''Alexandrovska'' Clinic of Haematology
  • University Multiprofile Hospital for Active Treament ''Sv. Marina'' - Varna Haematology Clinic
  • CHU Angers Services des Maladies du Sang
  • Hopital Saint Louis - Centre d'Investigation Clinique
  • University of Debrecen Medical and Health Science Centre
  • Petz Aladar County Teaching Hospital
  • Pandy Kalman Hospital of Bekes County
  • Kaposi Mor Teaching Hospital
  • Uniwersyteckie Centrum Kliniczne Katedra i Klinika Hematologii i Transplantologii
  • Samodzielny Publiczny Szpital Kliniczny Nr 1
  • Katedra i Klinika Onkologii i Chorob Wewnetrznych Akademii Medycznej
  • Klinika Hematologii Instytut Hematologii i Transfuzjologi
  • Hospitals da Universidade de Coimbra
  • Institute for Haematology of Clinical Centre of Serbia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

A

B

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
The LVEF was measured by echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function.
Platelet Count at Month 6
Platelet count was evaluated.

Secondary Outcome Measures

Change From Baseline in Platelet Counts at Month 3 and 36
Platelet count was evaluated throughout the study.
Percentage of Participants With Complete Response
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
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 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 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
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
White blood cell count was evaluated throughout the study.
Change From Baseline in Red Blood Cell Count Over Time
Red blood cell count was evaluated throughout the study.

Full Information

First Posted
September 12, 2005
Last Updated
May 13, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00202644
Brief Title
A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
January 13, 2006 (Actual)
Primary Completion Date
December 15, 2015 (Actual)
Study Completion Date
December 15, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombocythemia, Hemorrhagic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Title
B
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Anagrelide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Hydroxyurea
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Description
The LVEF was measured by echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function.
Time Frame
Baseline and Month 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36
Title
Platelet Count at Month 6
Description
Platelet count was evaluated.
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Change From Baseline in Platelet Counts at Month 3 and 36
Description
Platelet count was evaluated throughout the study.
Time Frame
Baseline and Month 3 and 36
Title
Percentage of Participants With Complete Response
Description
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.
Time Frame
Baseline up to Month 36
Title
Percentage of Participants With Partial Response
Description
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 Frame
Baseline up to Month 36
Title
Time to Complete Response
Description
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 Frame
Baseline up to Month 36
Title
Time to Partial Response
Description
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 Frame
Baseline up to Month 36
Title
Number of Participants With Thrombotic and Haemorrhagic Events
Description
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.
Time Frame
From the signing of informed consent until the last study-related visit (Month 36)
Title
Change From Baseline in White Blood Cell Count Over Time
Description
White blood cell count was evaluated throughout the study.
Time Frame
Baseline and Month 6, 12, 18, 24, 30 and 36
Title
Change From Baseline in Red Blood Cell Count Over Time
Description
Red blood cell count was evaluated throughout the study.
Time Frame
Baseline and Month 6, 12, 18, 24, 30 and 36

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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%
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
University Multiprofile Hospital for Active Treatment ''Dr Georgi Stranski'' - Pleven
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Facility Name
University Multiprofile Hospital for active Treatment ''Alexandrovska'' Clinic of Haematology
City
Sofia
ZIP/Postal Code
1303
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treament ''Sv. Marina'' - Varna Haematology Clinic
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
Facility Name
CHU Angers Services des Maladies du Sang
City
Angers
State/Province
Cedex 09
ZIP/Postal Code
49933
Country
France
Facility Name
Hopital Saint Louis - Centre d'Investigation Clinique
City
Paris
Country
France
Facility Name
University of Debrecen Medical and Health Science Centre
City
Debrecen
ZIP/Postal Code
4012
Country
Hungary
Facility Name
Petz Aladar County Teaching Hospital
City
Gyor
ZIP/Postal Code
9024
Country
Hungary
Facility Name
Pandy Kalman Hospital of Bekes County
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Kaposi Mor Teaching Hospital
City
Kaposvar
ZIP/Postal Code
7400
Country
Hungary
Facility Name
Uniwersyteckie Centrum Kliniczne Katedra i Klinika Hematologii i Transplantologii
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Samodzielny Publiczny Szpital Kliniczny Nr 1
City
Lublin
ZIP/Postal Code
21-081
Country
Poland
Facility Name
Katedra i Klinika Onkologii i Chorob Wewnetrznych Akademii Medycznej
City
Warsaw
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Klinika Hematologii Instytut Hematologii i Transfuzjologi
City
Warsaw
ZIP/Postal Code
02-776
Country
Poland
Facility Name
Hospitals da Universidade de Coimbra
City
Coimbra
ZIP/Postal Code
3000-076
Country
Portugal
Facility Name
Institute for Haematology of Clinical Centre of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia

12. IPD Sharing Statement

Citations:
PubMed Identifier
30368038
Citation
Birgegard 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.
Results Reference
result
PubMed Identifier
33123978
Citation
Gotic M, Egyed M, Gercheva L, Warzocha K, Kvasnicka HM, Achenbach H, Wu J. Cardiovascular Safety of Anagrelide Hydrochloride versus Hydroxyurea in Essential Thrombocythaemia. Cardiovasc Toxicol. 2021 Mar;21(3):236-247. doi: 10.1007/s12012-020-09615-0. Epub 2020 Oct 29.
Results Reference
derived

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

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