NCT00175838

Brief Summary

The purpose of this trial is to see if Hydroxyurea + aspirin is a better treatment than aspirin alone for Intermediate Risk Primary Thrombocythemia (PT) patients.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,398

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jul 1997

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 1997

Completed
8.2 years until next milestone

First Submitted

Initial submission to the registry

September 9, 2005

Completed
6 days until next milestone

First Posted

Study publicly available on registry

September 15, 2005

Completed
11.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
Last Updated

January 18, 2017

Status Verified

January 1, 2017

Enrollment Period

19.4 years

First QC Date

September 9, 2005

Last Update Submit

January 17, 2017

Conditions

ThrombocythemiaMyeloproliferative Disorder

Keywords

Primary ThrombocythmeiaHydroxyureaRandomisedThrombosisHaemorrhage

Outcome Measures

Primary Outcomes (1)

  • Does hydroxyurea reduce thrombosis and major haemorrhage when added to aspirin?

    Reducing thrombosis and major haemorrhage are specific key measurements in this group of patients for whom thrombotic events are very likely to occur.

    14 years

Secondary Outcomes (1)

  • Does treatment modality alter the risk of leukaemic or myelofibrotic transformation?

    14 years

Study Arms (2)

Intermediate risk group

ACTIVE COMPARATOR

Intermediate risk patients are randomised to a either a group receiving Aspirin only, or a group receiving both Hydroxyurea and Aspirin.

Drug: HydroxyureaDrug: Aspirin

Low risk group

ACTIVE COMPARATOR

Patients are given Aspirin only with observation.

Drug: Aspirin

Interventions

HydroxyureaDRUG

Hydroxyurea (or hydroxycarbamide) is an antineoplastic drug commonly used to treat haematological malignancies.

Also known as: Hydroxycarbamide
Intermediate risk group
AspirinDRUG

Aspirin is an anti-aggregating agent, and has been shown to reduce/alleviate minor ischaemic symptoms.

Intermediate risk groupLow risk group

Eligibility Criteria

Age40 Years - 59 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • The diagnostic criteria for primary thrombocythaemia are:
  • Platelet count \> 600x109/l.
  • No evidence of overt polycythaemia(confirmed by RCM if necessary)or of polycythaemia masked by co-existent iron deficiency.
  • No Philadelphia chromosome.
  • Absence of peripheral blood and/or marrow appearances of myelodysplasia, or myelofibrosis.
  • No known cause of reactive thrombocytosis. Particular care should be taken to exclude iron deficiency in pre-menopausal women.
  • Notes:
  • In asymptomatic patients, the platelet count should be observed for a period of at least 2 months to confirm \>600x109/l, and to allow any cause of reactive thrombocytosis to become overt.
  • If the PCV is above normal upper limit (that is, males \>0.51, females \>0.48) or in high normal range in a patient with palpable splenomegaly measure RCM. Iron deficient primary polycythaemia (polycythaemia vera) is strongly suggested if Hb/PCV is normal in the presence of iron deficient red cell changes. In this situation, iron therapy is potentially dangerous.
  • Exceeding rarely, bcr-abl positive Philadelphia chromosome negative patients present with high platelet counts with little or no elevation in WBC count. The features that suggest it is necessary to examine for bcr-abl, are:- basophilia, left-shift in WBC, granulocyte count \>16x109/l, difficulty in controlling platelet count, megakaryocytes of low ploidy (NAP is usually unhelpful).
  • A normal ESR, CRP or plasma viscosity is useful in excluding a reactive thrombocytosis.
  • Written informed consent obtained in accordance with NCRI requirements.
  • Patients with impaired hepatic / renal function are not excluded although the respective biochemical tests should be monitored during therapy and reduced doses of cytoreductive agent should be used, particularly in the case of hydroxyurea and renal dysfunction.

You may not qualify if:

  • High risk features (any of the following):
  • Age \>or= 60 years
  • Platelet count \> or= 1500x109/l (current or previous) (a)
  • History of ischaemia, thrombosis or embolic events (including erythromelalgia) (b)
  • Haemorrhage considered to be related to PT (b)
  • Presence of hypertension (c)or diabetes (d)
  • The manufacturers of hydroxyurea state that it should be avoided in pregnancy and in lactating women. Similarly, hydroxyurea should not be prescribed for women when there is doubt about their use of an effective contraceptive method.
  • Exclude patient from hydroxyurea therapy and, therefore, from the 'intermediate' risk randomisation if the patient has current leg ulcers.
  • Notes on the definition of high risk:
  • In patients with borderline counts the allocation of a patient to a high risk group based on platelet count alone should rely on at least three samples taken on separate occasions over at least 2 months.
  • Documentation of previous thrombo-embolic, ischaemic and haemorrhagic events should be given on the patient's entry proforma.
  • Hypertension is defined as those patients requiring hypotensive therapy.
  • Diabetes is defined as those patients requiring therapy with a hypoglycaemic agent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Addenbrooke's Hospital

Cambridge, Cambs, CB2 2QQ, United Kingdom

Location

Related Publications (1)

  • Godfrey AL, Campbell PJ, MacLean C, Buck G, Cook J, Temple J, Wilkins BS, Wheatley K, Nangalia J, Grinfeld J, McMullin MF, Forsyth C, Kiladjian JJ, Green AR, Harrison CN; United Kingdom Medical Research Council Primary Thrombocythemia-1 Study; United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup; French Intergroup of Myeloproliferative Neoplasms; the Australasian Leukaemia and Lymphoma Group.. Hydroxycarbamide Plus Aspirin Versus Aspirin Alone in Patients With Essential Thrombocythemia Age 40 to 59 Years Without High-Risk Features. J Clin Oncol. 2018 Dec 1;36(34):3361-3369. doi: 10.1200/JCO.2018.78.8414. Epub 2018 Aug 28.

    PMID: 30153096DERIVED

MeSH Terms

Conditions

ThrombocytosisMyeloproliferative DisordersThrombosisHemorrhage

Interventions

HydroxyureaAspirin

Condition Hierarchy (Ancestors)

Blood Platelet DisordersHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow DiseasesEmbolism and ThrombosisVascular DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic ChemicalsSalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbons

Study Officials

  • Anthony R Green, Prof

    Addenbrooke's Hospital and University of Cambridge

    STUDY DIRECTOR

  • Claire Harrison, Dr

    St Thomas' Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Haemato-Oncology

Study Record Dates

First Submitted

September 9, 2005

First Posted

September 15, 2005

Study Start

July 1, 1997

Primary Completion

November 1, 2016

Study Completion

November 1, 2016

Last Updated

January 18, 2017

Record last verified: 2017-01

Locations

GB(1)