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

Sponsor
Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT00202644
Collaborator
(none)
150
15
2
119
10
0.1

Study Details

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).

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
150 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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.
Actual Study Start Date :
Jan 13, 2006
Actual Primary Completion Date :
Dec 15, 2015
Actual Study Completion Date :
Dec 15, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: A

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.

Active Comparator: B

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.

Outcome Measures

Primary Outcome Measures

  1. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time [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.

  2. Platelet Count at Month 6 [Month 6]

    Platelet count was evaluated.

Secondary Outcome Measures

  1. Change From Baseline in Platelet Counts at Month 3 and 36 [Baseline and Month 3 and 36]

    Platelet count was evaluated throughout the study.

  2. Percentage of Participants With Complete Response [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.

  3. Percentage of Participants With Partial Response [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.

  4. Time to Complete Response [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).

  5. Time to Partial Response [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).

  6. Number of Participants With Thrombotic and Haemorrhagic Events [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.

  7. Change From Baseline in White Blood Cell Count Over Time [Baseline and Month 6, 12, 18, 24, 30 and 36]

    White blood cell count was evaluated throughout the study.

  8. Change From Baseline in Red Blood Cell Count Over Time [Baseline and Month 6, 12, 18, 24, 30 and 36]

    Red blood cell count was evaluated throughout the study.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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%

Contacts and Locations

Locations

Site City State Country Postal Code
1 University Multiprofile Hospital for Active Treatment ''Dr Georgi Stranski'' - Pleven Pleven Bulgaria 5800
2 University Multiprofile Hospital for active Treatment ''Alexandrovska'' Clinic of Haematology Sofia Bulgaria 1303
3 University Multiprofile Hospital for Active Treament ''Sv. Marina'' - Varna Haematology Clinic Varna Bulgaria 9010
4 CHU Angers Services des Maladies du Sang Angers Cedex 09 France 49933
5 Hopital Saint Louis - Centre d'Investigation Clinique Paris France
6 University of Debrecen Medical and Health Science Centre Debrecen Hungary 4012
7 Petz Aladar County Teaching Hospital Gyor Hungary 9024
8 Pandy Kalman Hospital of Bekes County Gyula Hungary 5700
9 Kaposi Mor Teaching Hospital Kaposvar Hungary 7400
10 Uniwersyteckie Centrum Kliniczne Katedra i Klinika Hematologii i Transplantologii Gdansk Poland 80-952
11 Samodzielny Publiczny Szpital Kliniczny Nr 1 Lublin Poland 21-081
12 Katedra i Klinika Onkologii i Chorob Wewnetrznych Akademii Medycznej Warsaw Poland 02-097
13 Klinika Hematologii Instytut Hematologii i Transfuzjologi Warsaw Poland 02-776
14 Hospitals da Universidade de Coimbra Coimbra Portugal 3000-076
15 Institute for Haematology of Clinical Centre of Serbia Belgrade Serbia 11000

Sponsors and Collaborators

  • Shire

Investigators

  • Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Shire
ClinicalTrials.gov Identifier:
NCT00202644
Other Study ID Numbers:
  • SPD422-403
  • 2004-004061-15
First Posted:
Sep 20, 2005
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail A total of 183 participants were screened, 149 participants were randomized at 29 sites across 10 countries. Four (4) participants randomized but withdrawn prior to treatment and 1 participant not randomized but treated.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Period Title: Overall Study
STARTED 76 70
COMPLETED 41 43
NOT COMPLETED 35 27

Baseline Characteristics

Arm/Group Title Anagrelide Hydroxyurea Total
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. Total of all reporting groups
Overall Participants 76 70 146
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
52.1
(16.10)
52.9
(15.80)
52.5
(15.91)
Sex: Female, Male (Count of Participants)
Female
56
73.7%
45
64.3%
101
69.2%
Male
20
26.3%
25
35.7%
45
30.8%

Outcome Measures

1. Primary Outcome
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

Outcome Measure Data

Analysis Population Description
The Full Analysis Set (FAS) population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. Here, n = Number of participants analysed for specified category at the specified time points in each arm respectively.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Baseline
66.4
(4.81)
66.9
(4.59)
Change from baseline at Month 1
0.5
(4.68)
-1.1
(4.73)
Change from baseline at Month 2
1.2
(5.80)
0
(5.03)
Change from baseline at Month 3
0.1
(5.31)
-0.4
(3.94)
Change from baseline at Month 6
-0.5
(5.68)
-0.6
(3.95)
Change from baseline at Month 9
-0.8
(4.78)
-1.5
(5.15)
Change from baseline at Month 12
-0.8
(6.61)
-0.6
(5.67)
Change from baseline at Month 18
-2.0
(5.54)
-1.2
(4.84)
Change from baseline at Month 24
-1.8
(6.81)
-1.7
(6.17)
Change from baseline at Month 30
-1.8
(5.84)
-0.2
(5.38)
Change from baseline at Month 36
-1.7
(6.55)
-0.6
(5.46)
2. Primary Outcome
Title Platelet Count at Month 6
Description Platelet count was evaluated.
Time Frame Month 6

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. Here, N = Number of participants analysed in each arm for this outcome measure.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 60 58
Mean (Standard Deviation) [10^9 platelets per liter]
418.6
(135.96)
396.0
(144.07)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anagrelide, Hydroxyurea
Comments
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Noninferiority of anagrelide could be concluded if lower limit of 95% Confidence Interval for the difference between treatment groups (Hydroxyurea - Anagrelide) was > -100 x 10^9/Liter.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value -100.5
Confidence Interval (2-Sided) 95%
-179.42 to -21.49
Parameter Dispersion Type: Standard Error of the Mean
Value: 39.93
Estimation Comments
3. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded with last observation carried forward (LOCF). Here, n=number of participants analysed for specified category at specified time points in each arm respectively.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Change from baseline at Month 3
575.3
(36.11)
462.2
(37.54)
Change from baseline at Month 36
531.0
(42.14)
462.8
(43.81)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anagrelide, Hydroxyurea
Comments Month 3
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Noninferiority of anagrelide could be concluded if lower limit of 95% Confidence Interval for the difference between treatment groups (Hydroxyurea - Anagrelide) was > -100 x 10^9/Liter.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value -113.1
Confidence Interval (2-Sided) 95%
-187.40 to -38.83
Parameter Dispersion Type: Standard Error of the Mean
Value: 37.56
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Anagrelide, Hydroxyurea
Comments Month 36
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Noninferiority of anagrelide could be concluded if lower limit of 95% Confidence Interval for the difference between treatment groups (Hydroxyurea - Anagrelide) was > -100 x 10^9/Liter.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Least Square Mean
Estimated Value -68.3
Confidence Interval (2-Sided) 95%
-154.95 to 18.43
Parameter Dispersion Type: Standard Error of the Mean
Value: 43.83
Estimation Comments
4. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Number [percenatge of participants]
58.9
77.5%
58.8
84%
5. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Number [percentage of participants]
21.9
28.8%
27.9
39.9%
6. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Median (95% Confidence Interval) [days]
177.0
123.0
7. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Median (95% Confidence Interval) [days]
61.0
47.0
8. Secondary Outcome
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)

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Number [participants]
30
39.5%
16
22.9%
9. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. Here, n = Number of participants analysed for specified category at the specified time points in each arm respectively.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Baseline
9.13
(2.159)
10.20
(3.491)
Change from baseline at Month 6
-0.38
(4.257)
-5.02
(2.525)
Change from baseline at Month 12
-1.00
(2.001)
-4.79
(2.779)
Change from baseline at Month 18
-1.18
(2.184)
-4.46
(2.664)
Change from baseline at Month 24
-1.24
(2.283)
-4.82
(2.692)
Change from baseline at Month 30
-1.00
(2.316)
-4.59
(3.391)
Change from baseline at Month 36
-1.63
(2.234)
-4.46
(3.312)
10. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. Here, n = Number of participants analysed for specified category at the specified time points in each arm respectively.
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
Measure Participants 73 68
Baseline
4.757
(0.5897)
4.787
(0.6002)
Change from baseline at Month 6
-0.227
(0.4134)
-1.467
(0.6563)
Change from baseline at Month 12
-0.246
(0.4292)
-1.398
(0.5744)
Change from baseline at Month 18
-0.225
(0.4224)
-1.323
(0.7278)
Change from baseline at Month 24
-0.299
(0.5811)
-1.281
(0.7219)
Change from baseline at Month 30
-0.295
(0.5713)
-1.339
(0.6509)
Change from baseline at Month 36
-0.366
(0.4328)
-1.362
(0.6586)

Adverse Events

Time Frame From the signing of informed consent until the last study-related visit (Month 36)
Adverse Event Reporting Description
Arm/Group Title Anagrelide Hydroxyurea
Arm/Group Description Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years.
All Cause Mortality
Anagrelide Hydroxyurea
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Anagrelide Hydroxyurea
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 17/76 (22.4%) 13/70 (18.6%)
Blood and lymphatic system disorders
Anaemia 1/76 (1.3%) 1 0/70 (0%) 0
Iron deficiency anaemia 1/76 (1.3%) 1 0/70 (0%) 0
Pancytopenia 0/76 (0%) 0 1/70 (1.4%) 1
Cardiac disorders
Angina unstable 1/76 (1.3%) 1 0/70 (0%) 0
Left ventricular failure 1/76 (1.3%) 1 0/70 (0%) 0
Tachycardia 1/76 (1.3%) 1 0/70 (0%) 0
Gastrointestinal disorders
Anal fistula 0/76 (0%) 0 1/70 (1.4%) 2
Crohn's disease 1/76 (1.3%) 1 0/70 (0%) 0
Gastrointestinal haemorrhage 0/76 (0%) 0 1/70 (1.4%) 1
Inguinal hernia 0/76 (0%) 0 1/70 (1.4%) 1
Upper gastrointestinal haemorrhage 1/76 (1.3%) 1 0/70 (0%) 0
General disorders
Asthenia 1/76 (1.3%) 1 0/70 (0%) 0
Sudden death 1/76 (1.3%) 1 0/70 (0%) 0
Infections and infestations
Ear infection 1/76 (1.3%) 1 0/70 (0%) 0
Laryngitis 1/76 (1.3%) 1 0/70 (0%) 0
Sepsis 1/76 (1.3%) 1 0/70 (0%) 0
Injury, poisoning and procedural complications
Foot fracture 0/76 (0%) 0 1/70 (1.4%) 1
Traumatic amputation 0/76 (0%) 0 1/70 (1.4%) 1
Traumatic haematoma 1/76 (1.3%) 2 0/70 (0%) 0
Metabolism and nutrition disorders
Hyperglycaemia 1/76 (1.3%) 1 0/70 (0%) 0
Type 2 diabetes mellitus 1/76 (1.3%) 1 0/70 (0%) 0
Musculoskeletal and connective tissue disorders
Scleroderma 0/76 (0%) 0 1/70 (1.4%) 1
Tendon calcification 0/76 (0%) 0 1/70 (1.4%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoid cystic carcinoma 1/76 (1.3%) 1 0/70 (0%) 0
Bladder cancer 1/76 (1.3%) 1 0/70 (0%) 0
Breast cancer 0/76 (0%) 0 1/70 (1.4%) 1
Malignant melanoma 0/76 (0%) 0 1/70 (1.4%) 1
Peripheral nerve sheath tumour malignant 0/76 (0%) 0 1/70 (1.4%) 1
Nervous system disorders
Aphasia 1/76 (1.3%) 1 0/70 (0%) 0
Cerebral infarction 1/76 (1.3%) 2 0/70 (0%) 0
Ischaemic stroke 3/76 (3.9%) 3 0/70 (0%) 0
Neurological decompensation 1/76 (1.3%) 1 0/70 (0%) 0
Vasculitis cerebral 1/76 (1.3%) 1 0/70 (0%) 0
Reproductive system and breast disorders
Ovarian cyst 1/76 (1.3%) 1 0/70 (0%) 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism 1/76 (1.3%) 1 1/70 (1.4%) 1
Respiratory distress 1/76 (1.3%) 1 0/70 (0%) 0
Vascular disorders
Deep vein thrombosis 0/76 (0%) 0 1/70 (1.4%) 1
Hypertensive crisis 1/76 (1.3%) 1 0/70 (0%) 0
Peripheral artery thrombosis 1/76 (1.3%) 1 0/70 (0%) 0
Other (Not Including Serious) Adverse Events
Anagrelide Hydroxyurea
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 46/76 (60.5%) 27/70 (38.6%)
Blood and lymphatic system disorders
Anaemia 4/76 (5.3%) 6 8/70 (11.4%) 9
Leukopenia 1/76 (1.3%) 1 7/70 (10%) 7
Neutropenia 0/76 (0%) 0 5/70 (7.1%) 8
Cardiac disorders
Palpitations 18/76 (23.7%) 29 0/70 (0%) 0
Ear and labyrinth disorders
Vertigo 5/76 (6.6%) 5 0/70 (0%) 0
Gastrointestinal disorders
Diarrhoea 6/76 (7.9%) 7 3/70 (4.3%) 3
General disorders
Asthenia 5/76 (6.6%) 6 4/70 (5.7%) 6
Chest pain 4/76 (5.3%) 7 1/70 (1.4%) 1
Infections and infestations
Nasopharyngitis 2/76 (2.6%) 2 5/70 (7.1%) 8
Pharyngitis 2/76 (2.6%) 2 6/70 (8.6%) 8
Upper respiratory tract infection 4/76 (5.3%) 4 1/70 (1.4%) 1
Urinary tract infection 4/76 (5.3%) 8 2/70 (2.9%) 2
Musculoskeletal and connective tissue disorders
Arthralgia 6/76 (7.9%) 7 2/70 (2.9%) 2
Nervous system disorders
Headache 19/76 (25%) 33 1/70 (1.4%) 1
Respiratory, thoracic and mediastinal disorders
Epistaxis 4/76 (5.3%) 5 2/70 (2.9%) 2
Vascular disorders
Hypertension 9/76 (11.8%) 12 1/70 (1.4%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.

Results Point of Contact

Name/Title Study Director
Organization Shire
Phone +1 866 842 5335
Email ClinicalTransparency@shire.com
Responsible Party:
Shire
ClinicalTrials.gov Identifier:
NCT00202644
Other Study ID Numbers:
  • SPD422-403
  • 2004-004061-15
First Posted:
Sep 20, 2005
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021