Trial Outcomes & Findings for A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients (NCT NCT00202644)
NCT ID: NCT00202644
Last Updated: 2021-06-02
Results Overview
The LVEF was measured by echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
150 participants
Primary outcome timeframe
Baseline and Month 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36
Results posted on
2021-06-02
Participant Flow
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 Four (4) participants randomized but withdrawn prior to treatment and 1 participant not randomized but treated.
Participant milestones
| Measure |
Anagrelide
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.
|
Hydroxyurea
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.
|
|---|---|---|
|
Overall Study
STARTED
|
76
|
70
|
|
Overall Study
COMPLETED
|
41
|
43
|
|
Overall Study
NOT COMPLETED
|
35
|
27
|
Reasons for withdrawal
| Measure |
Anagrelide
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.
|
Hydroxyurea
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
12
|
13
|
|
Overall Study
Withdrawal by Subject
|
8
|
6
|
|
Overall Study
Lack of Efficacy
|
6
|
6
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Other
|
9
|
1
|
Baseline Characteristics
A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients
Baseline characteristics by cohort
| Measure |
Anagrelide
n=76 Participants
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.
|
Hydroxyurea
n=70 Participants
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
n=146 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.1 years
STANDARD_DEVIATION 16.10 • n=5 Participants
|
52.9 years
STANDARD_DEVIATION 15.80 • n=7 Participants
|
52.5 years
STANDARD_DEVIATION 15.91 • n=5 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Month 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36Population: 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.
The LVEF was measured by echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function.
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 3
|
0.1 percentage of ejection fraction
Standard Deviation 5.31
|
-0.4 percentage of ejection fraction
Standard Deviation 3.94
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 6
|
-0.5 percentage of ejection fraction
Standard Deviation 5.68
|
-0.6 percentage of ejection fraction
Standard Deviation 3.95
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Baseline
|
66.4 percentage of ejection fraction
Standard Deviation 4.81
|
66.9 percentage of ejection fraction
Standard Deviation 4.59
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 1
|
0.5 percentage of ejection fraction
Standard Deviation 4.68
|
-1.1 percentage of ejection fraction
Standard Deviation 4.73
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 2
|
1.2 percentage of ejection fraction
Standard Deviation 5.80
|
0 percentage of ejection fraction
Standard Deviation 5.03
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 9
|
-0.8 percentage of ejection fraction
Standard Deviation 4.78
|
-1.5 percentage of ejection fraction
Standard Deviation 5.15
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 12
|
-0.8 percentage of ejection fraction
Standard Deviation 6.61
|
-0.6 percentage of ejection fraction
Standard Deviation 5.67
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 18
|
-2.0 percentage of ejection fraction
Standard Deviation 5.54
|
-1.2 percentage of ejection fraction
Standard Deviation 4.84
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 24
|
-1.8 percentage of ejection fraction
Standard Deviation 6.81
|
-1.7 percentage of ejection fraction
Standard Deviation 6.17
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 30
|
-1.8 percentage of ejection fraction
Standard Deviation 5.84
|
-0.2 percentage of ejection fraction
Standard Deviation 5.38
|
|
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Change from baseline at Month 36
|
-1.7 percentage of ejection fraction
Standard Deviation 6.55
|
-0.6 percentage of ejection fraction
Standard Deviation 5.46
|
PRIMARY outcome
Timeframe: Month 6Population: 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.
Platelet count was evaluated.
Outcome measures
| Measure |
Anagrelide
n=60 Participants
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.
|
Hydroxyurea
n=58 Participants
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.
|
|---|---|---|
|
Platelet Count at Month 6
|
418.6 10^9 platelets per liter
Standard Deviation 135.96
|
396.0 10^9 platelets per liter
Standard Deviation 144.07
|
SECONDARY outcome
Timeframe: Baseline and Month 3 and 36Population: 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.
Platelet count was evaluated throughout the study.
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Change From Baseline in Platelet Counts at Month 3 and 36
Change from baseline at Month 3
|
575.3 10^9 platelets per liter
Standard Deviation 36.11
|
462.2 10^9 platelets per liter
Standard Deviation 37.54
|
|
Change From Baseline in Platelet Counts at Month 3 and 36
Change from baseline at Month 36
|
531.0 10^9 platelets per liter
Standard Deviation 42.14
|
462.8 10^9 platelets per liter
Standard Deviation 43.81
|
SECONDARY outcome
Timeframe: Baseline up to Month 36Population: 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.
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.
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Percentage of Participants With Complete Response
|
58.9 percenatge of participants
|
58.8 percenatge of participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 36Population: 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.
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.
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Percentage of Participants With Partial Response
|
21.9 percentage of participants
|
27.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 36Population: 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.
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).
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Time to Complete Response
|
177.0 days
Interval 129.0 to 548.0
|
123.0 days
Interval 90.0 to 554.0
|
SECONDARY outcome
Timeframe: Baseline up to Month 36Population: 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.
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).
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Time to Partial Response
|
61.0 days
Interval 43.0 to 85.0
|
47.0 days
Interval 41.0 to 57.0
|
SECONDARY outcome
Timeframe: From the signing of informed consent until the last study-related visit (Month 36)Population: 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.
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.
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Number of Participants With Thrombotic and Haemorrhagic Events
|
30 participants
|
16 participants
|
SECONDARY outcome
Timeframe: Baseline and Month 6, 12, 18, 24, 30 and 36Population: 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.
White blood cell count was evaluated throughout the study.
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Change From Baseline in White Blood Cell Count Over Time
Baseline
|
9.13 10^9 cells per liter
Standard Deviation 2.159
|
10.20 10^9 cells per liter
Standard Deviation 3.491
|
|
Change From Baseline in White Blood Cell Count Over Time
Change from baseline at Month 6
|
-0.38 10^9 cells per liter
Standard Deviation 4.257
|
-5.02 10^9 cells per liter
Standard Deviation 2.525
|
|
Change From Baseline in White Blood Cell Count Over Time
Change from baseline at Month 12
|
-1.00 10^9 cells per liter
Standard Deviation 2.001
|
-4.79 10^9 cells per liter
Standard Deviation 2.779
|
|
Change From Baseline in White Blood Cell Count Over Time
Change from baseline at Month 18
|
-1.18 10^9 cells per liter
Standard Deviation 2.184
|
-4.46 10^9 cells per liter
Standard Deviation 2.664
|
|
Change From Baseline in White Blood Cell Count Over Time
Change from baseline at Month 24
|
-1.24 10^9 cells per liter
Standard Deviation 2.283
|
-4.82 10^9 cells per liter
Standard Deviation 2.692
|
|
Change From Baseline in White Blood Cell Count Over Time
Change from baseline at Month 30
|
-1.00 10^9 cells per liter
Standard Deviation 2.316
|
-4.59 10^9 cells per liter
Standard Deviation 3.391
|
|
Change From Baseline in White Blood Cell Count Over Time
Change from baseline at Month 36
|
-1.63 10^9 cells per liter
Standard Deviation 2.234
|
-4.46 10^9 cells per liter
Standard Deviation 3.312
|
SECONDARY outcome
Timeframe: Baseline and Month 6, 12, 18, 24, 30 and 36Population: 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.
Red blood cell count was evaluated throughout the study.
Outcome measures
| Measure |
Anagrelide
n=73 Participants
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.
|
Hydroxyurea
n=68 Participants
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.
|
|---|---|---|
|
Change From Baseline in Red Blood Cell Count Over Time
Change from baseline at Month 36
|
-0.366 10^12 cells per liter
Standard Deviation 0.4328
|
-1.362 10^12 cells per liter
Standard Deviation 0.6586
|
|
Change From Baseline in Red Blood Cell Count Over Time
Baseline
|
4.757 10^12 cells per liter
Standard Deviation 0.5897
|
4.787 10^12 cells per liter
Standard Deviation 0.6002
|
|
Change From Baseline in Red Blood Cell Count Over Time
Change from baseline at Month 6
|
-0.227 10^12 cells per liter
Standard Deviation 0.4134
|
-1.467 10^12 cells per liter
Standard Deviation 0.6563
|
|
Change From Baseline in Red Blood Cell Count Over Time
Change from baseline at Month 12
|
-0.246 10^12 cells per liter
Standard Deviation 0.4292
|
-1.398 10^12 cells per liter
Standard Deviation 0.5744
|
|
Change From Baseline in Red Blood Cell Count Over Time
Change from baseline at Month 18
|
-0.225 10^12 cells per liter
Standard Deviation 0.4224
|
-1.323 10^12 cells per liter
Standard Deviation 0.7278
|
|
Change From Baseline in Red Blood Cell Count Over Time
Change from baseline at Month 24
|
-0.299 10^12 cells per liter
Standard Deviation 0.5811
|
-1.281 10^12 cells per liter
Standard Deviation 0.7219
|
|
Change From Baseline in Red Blood Cell Count Over Time
Change from baseline at Month 30
|
-0.295 10^12 cells per liter
Standard Deviation 0.5713
|
-1.339 10^12 cells per liter
Standard Deviation 0.6509
|
Adverse Events
Anagrelide
Serious events: 17 serious events
Other events: 46 other events
Deaths: 0 deaths
Hydroxyurea
Serious events: 13 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Anagrelide
n=76 participants at risk
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.
|
Hydroxyurea
n=70 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Cardiac disorders
Angina unstable
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Cardiac disorders
Left ventricular failure
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Cardiac disorders
Tachycardia
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 2 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Gastrointestinal disorders
Crohn's disease
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
General disorders
Asthenia
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
General disorders
Sudden death
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Infections and infestations
Ear infection
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Infections and infestations
Laryngitis
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Infections and infestations
Sepsis
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Injury, poisoning and procedural complications
Traumatic amputation
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
1.3%
1/76 • Number of events 2 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Musculoskeletal and connective tissue disorders
Scleroderma
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Musculoskeletal and connective tissue disorders
Tendon calcification
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoid cystic carcinoma
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Peripheral nerve sheath tumour malignant
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Nervous system disorders
Aphasia
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Nervous system disorders
Cerebral infarction
|
1.3%
1/76 • Number of events 2 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Nervous system disorders
Ischaemic stroke
|
3.9%
3/76 • Number of events 3 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Nervous system disorders
Neurological decompensation
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Nervous system disorders
Vasculitis cerebral
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Reproductive system and breast disorders
Ovarian cyst
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Vascular disorders
Hypertensive crisis
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Vascular disorders
Peripheral artery thrombosis
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
Other adverse events
| Measure |
Anagrelide
n=76 participants at risk
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.
|
Hydroxyurea
n=70 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.3%
4/76 • Number of events 6 • From the signing of informed consent until the last study-related visit (Month 36)
|
11.4%
8/70 • Number of events 9 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.3%
1/76 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
10.0%
7/70 • Number of events 7 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/76 • From the signing of informed consent until the last study-related visit (Month 36)
|
7.1%
5/70 • Number of events 8 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Cardiac disorders
Palpitations
|
23.7%
18/76 • Number of events 29 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Ear and labyrinth disorders
Vertigo
|
6.6%
5/76 • Number of events 5 • From the signing of informed consent until the last study-related visit (Month 36)
|
0.00%
0/70 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Gastrointestinal disorders
Diarrhoea
|
7.9%
6/76 • Number of events 7 • From the signing of informed consent until the last study-related visit (Month 36)
|
4.3%
3/70 • Number of events 3 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
General disorders
Asthenia
|
6.6%
5/76 • Number of events 6 • From the signing of informed consent until the last study-related visit (Month 36)
|
5.7%
4/70 • Number of events 6 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
General disorders
Chest pain
|
5.3%
4/76 • Number of events 7 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Infections and infestations
Nasopharyngitis
|
2.6%
2/76 • Number of events 2 • From the signing of informed consent until the last study-related visit (Month 36)
|
7.1%
5/70 • Number of events 8 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Infections and infestations
Pharyngitis
|
2.6%
2/76 • Number of events 2 • From the signing of informed consent until the last study-related visit (Month 36)
|
8.6%
6/70 • Number of events 8 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Infections and infestations
Upper respiratory tract infection
|
5.3%
4/76 • Number of events 4 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Infections and infestations
Urinary tract infection
|
5.3%
4/76 • Number of events 8 • From the signing of informed consent until the last study-related visit (Month 36)
|
2.9%
2/70 • Number of events 2 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.9%
6/76 • Number of events 7 • From the signing of informed consent until the last study-related visit (Month 36)
|
2.9%
2/70 • Number of events 2 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Nervous system disorders
Headache
|
25.0%
19/76 • Number of events 33 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.3%
4/76 • Number of events 5 • From the signing of informed consent until the last study-related visit (Month 36)
|
2.9%
2/70 • Number of events 2 • From the signing of informed consent until the last study-related visit (Month 36)
|
|
Vascular disorders
Hypertension
|
11.8%
9/76 • Number of events 12 • From the signing of informed consent until the last study-related visit (Month 36)
|
1.4%
1/70 • Number of events 1 • From the signing of informed consent until the last study-related visit (Month 36)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER