Thrombocythemia, HemorrhagicPhase 4NCT00202644
A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients
A Phase 4 study testing Anagrelide and Hydroxyurea in people with Thrombocythemia, Hemorrhagic, run by Shire at 15 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thrombocythemia, Hemorrhagic
- What is being tested?
- Anagrelide and Hydroxyurea
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 15 sitesin 6 countries
- Study dates
- 13 Jan 2006to 15 Dec 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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%
Trial locations and contacts
15 sites in 6 countries.
15 sites in 6 countries
Hungary4 sites
University of Debrecen Medical and Health Science Centre
Debrecen, 4012
Petz Aladar County Teaching Hospital
Győr, 9024
Pandy Kalman Hospital of Bekes County
Gyula, 5700
Kaposi Mor Teaching Hospital
Kaposvár, 7400
Poland4 sites
Uniwersyteckie Centrum Kliniczne Katedra i Klinika Hematologii i Transplantologii
Gdansk, 80-952
Samodzielny Publiczny Szpital Kliniczny Nr 1
Lublin, 21-081
Katedra i Klinika Onkologii i Chorob Wewnetrznych Akademii Medycznej
Warsaw, 02-097
Klinika Hematologii Instytut Hematologii i Transfuzjologi
Warsaw, 02-776
Bulgaria3 sites
University Multiprofile Hospital for Active Treatment ''Dr Georgi Stranski'' - Pleven
Pleven, 5800
University Multiprofile Hospital for active Treatment ''Alexandrovska'' Clinic of Haematology
Sofia, 1303
University Multiprofile Hospital for Active Treament ''Sv. Marina'' - Varna Haematology Clinic
Varna, 9010
France2 sites
CHU Angers Services des Maladies du Sang
Angers, Cedex 09, 49933
Hopital Saint Louis - Centre d'Investigation Clinique
Paris
Serbia1 site
Institute for Haematology of Clinical Centre of Serbia
Belgrade, 11000
About this study
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.
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).
- Conditions
- Thrombocythemia, Hemorrhagic
- Being tested
- Anagrelide, Hydroxyurea
- Medical subject headings
- Thrombocythemia, Essential
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnagrelideDrug
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.
HydroxyureaDrug
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 group | Role | What they receive |
|---|---|---|
| A | Experimental | Not described Receives: Drug: Anagrelide |
| B | Active comparator | Not described Receives: Drug: Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Month 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36
Platelet Count at Month 6
Platelet count was evaluated.
Measured: Month 6
Secondary outcomes (8)
Change From Baseline in Platelet Counts at Month 3 and 36
Platelet count was evaluated throughout the study.
Measured: Baseline and Month 3 and 36
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.
Measured: Baseline up to Month 36
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.
Measured: Baseline up to Month 36
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).
Measured: Baseline up to Month 36
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).
Measured: Baseline up to Month 36
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.
Measured: From the signing of informed consent until the last study-related visit (Month 36)
Change From Baseline in White Blood Cell Count Over Time
White blood cell count was evaluated throughout the study.
Measured: Baseline and Month 6, 12, 18, 24, 30 and 36
Change From Baseline in Red Blood Cell Count Over Time
Red blood cell count was evaluated throughout the study.
Measured: Baseline and Month 6, 12, 18, 24, 30 and 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study start13 Jan 2006
- Primary completion15 Dec 2015
- Study completion15 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Thrombocythemia, HemorrhagicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00202644
- Sponsor's protocol ID
- SPD422-403
- Other IDs
- 2004-004061-15, 2004
- Status last verified
- May 2021
- First submitted
- 12 Sep 2005
- Last updated
- 2 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 30368038Gotic 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.
PubMed 33123978
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00202644
- Acronym / sponsor ID
- SPD422-403
- Conditions
- Thrombocythemia, Hemorrhagic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 13 Jan 2006 (actual)
- Primary completion
- 15 Dec 2015 (actual)
- Study completion
- 15 Dec 2015 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Posted 24 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Anagrelide |
| B | Active comparator | Drug: Hydroxyurea |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnagrelideAnagrelide 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 | A |
| HydroxyureaHydroxyurea is 500mg hydroxycarbamide capsules; initial dose is 1000mg/day, administered in two divided doses (500mg/dose). Dose titrated to effect to achieve a response. | Drug | B |
Primary outcome
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.
8 secondary outcomes
Change From Baseline in Platelet Counts at Month 3 and 36
Time frame: Baseline and Month 3 and 36
Percentage of Participants With Complete Response
Time frame: Baseline up to Month 36
Percentage of Participants With Partial Response
Time frame: Baseline up to Month 36
Time to Complete Response
Time frame: Baseline up to Month 36
Time to Partial Response
Time frame: Baseline up to Month 36
Number of Participants With Thrombotic and Haemorrhagic Events
Time frame: From the signing of informed consent until the last study-related visit (Month 36)
Change From Baseline in White Blood Cell Count Over Time
Time frame: Baseline and Month 6, 12, 18, 24, 30 and 36
Change From Baseline in Red Blood Cell Count Over Time
Time frame: Baseline and Month 6, 12, 18, 24, 30 and 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30368038Birgegard 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.
- Derived from this study: PubMed 33123978Gotic 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
15 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Anagrelide and Hydroxyurea in people with Thrombocythemia, Hemorrhagic, run by Shire at 15 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Hungary, Poland, Bulgaria, France, Portugal and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00202644, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.