Condition category
Cancer
Date applied
25/03/2015
Date assigned
25/03/2015
Last edited
04/11/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Ms Gillian Powter

ORCID ID

Contact details

John Radcliffe Hospital
National Blood Service – Oxford Centre
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Type

Public

Additional contact

Ms Jo Brown

ORCID ID

Contact details

NHSBT
Clinical Trials Unit
Long Road
Cambridge
CB2 0PT
United Kingdom

Type

Public

Additional contact

Ms Claire Dyer

ORCID ID

Contact details

NHSBT Clinical Trials Unit
Research Office
Level 2
John Radcliffe Hospital
Oxford
OX3 9BQ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

18157

Study information

Scientific title

A double blind, randomised controlled TRial EvaluAting the safety and efficacy of Tranexamic acid in patients with haematological malignancies with severe
Thrombocytopenia

Acronym

TREATT

Study hypothesis

Patients with cancers of the blood often develop low blood cell counts either as a consequence of the disease or the treatment by chemotherapy or stem cell transplantation. Platelet transfusions are commonly given to raise any low platelet count and reduce the risk of clinical bleeding (prophylaxis) or stop active bleeding (therapy). But recent studies have indicated that many patients continue to experience bleeding, despite the use of platelet transfusions. Tranexamic acid is a type of drug that is called an antifibrinolytic. These drugs act to reduce the breakdown of clots formed in response to bleeding. These drugs have been used widely in both elective and emergency surgery and have been shown to decrease blood loss and the use of red cell transfusions. The purpose of this study is to test whether giving tranexamic acid to patients receiving treatment for blood cancers reduces the risk of bleeding or death, and the need for platelet transfusions. Patients will be randomised to receive tranexamic acid (given intravenously through a drip, or orally) or a placebo. We will measure the rates of bleeding daily using a short structured assessment of bleeding, and we will record the number of transfusions given to patients.

Ethics approval

South-Central Oxford C, 16/03/2015, ref: 14/SC/1290

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet

Condition

Patients with haematological malignancies receiving intensive chemotherapy and/or stem cell transplantation.

Intervention

Prophylactic TXA/Placebo, double-blind, placebo controlled parallel group trial to assess the safety and efficacy of tranexamic acid at reducing bleeding in patients with haematological malignancies and severe thrombocytopenia. Participants will be randomised to receive TXA or placebo. Trial treatment will be started as per randomisation assignment as soon as possible within 24 hours of the first recorded platelet count = 30 x 109/L.
Dose schedule TXA 1g every eight hours IV or 1.5g every eight hours PO.
Follow Up Length: 4 month(s); Study Entry : Single Randomisation only

Intervention type

Drug

Phase

Phase III

Drug names

Tranexamic acid

Primary outcome measures

Proportion of patients who died or had bleeding of WHO grade 2 or above during the first 30 days of the trial. Day 1 being the first day the patient’s platelet count falls to ≤30x109/L.

A time-to-event analysis will be used to determine this proportion to ensure that all patients are included in the primary outcome analysis, not just those who are followed up for the full 30 days. Any patients lost to follow-up will be included in the analysis and censored at the time that they were lost.

Secondary outcome measures

1. Secondary Efficacy Outcomes
All measured during first 30 days of the trial. Day 1 being the first day the patient’s platelet count falls to ≤30x109/L.)
1.1. Proportion of days with bleeding (WHO grade 2 or above)
1.2. Time to first episode of bleeding of WHO grade 2 or greater for those patients who bled
1.3. Highest grade of bleeding a patient experiences
1.4. Number of platelet transfusions/patient
1.5. Number of red cell transfusions/patient
1.6. Proportion of patients surviving at least 30 days without a platelet transfusion
1.7. Proportion of patients surviving at least 30 days without a red cell transfusion
2. Secondary Safety Outcomes
2.1. Number of thrombotic events from first administration of trial treatment up to and including 120 days after the first dose of trial treatment is administered, per day at risk
2.2. Number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of first administration of trial treatment
2.3. All-cause mortality during the first 30 days and the first 120 days after the first dose of trial treatment is administered
2.4. Death due to thrombosis during the first 120 days after the first dose of trial treatment is administered
2.5. Death due to bleeding during the first 30 days after the first dose of trial treatment is administered
2.6. Number of serious adverse events from first administration of trial treatment until 60 days after the first dose of trial treatment is administered
3. Other outcomes
All measured during first 30 days of the trial. Day 1 being the first day the patient’s platelet count falls to ≤30x109/L.)
3.1. Number of days with thrombocytopenia (≤10x109/L, ≤30x109/L, ≤50x109/L)
3.2. Reasons for platelet and red cell transfusions

Overall trial start date

30/04/2015

Overall trial end date

28/02/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. At least 18 years of age
2. Confirmed diagnosis of a haematological malignancy
3. Undergoing chemotherapy or haematopoietic stem cell transplantation
4. Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of ≤10x10 to the power of 9/L for ≥ 5 days
5. Able to comply with treatment and monitoring

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 816; UK Sample Size: 616; Description: Based on the experience of similar patients in the TOPPS trial, in the absence of antifibrinolytic therapy, it is anticipated that 43% of eligible patients would experience death or WHO Grade 2 bleeding or higher within the first 30 days. In such a background setting of bleeding, the trial investigators anticipate less than a 10% relative reduction in bleeding rates would not be sufficient to substantially change clinical practice, because the absolute risk reduction of 4.3% would mean that it w

Participant exclusion criteria

1. Diagnosis of acute promyelocytic leukaemia and undergoing induction chemotherapy
2. History of ITP, TTP or HUS
3. Patients receiving L-asparginase as part of their current cycle of treatment
4. Patients with a past history or current diagnosis of arterial or venous thromboembolic disease including myocardial infarction, peripheral vascular disease and retinal arterial or venous thrombosis
5. Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome)
6. Patients receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex
Concentrates (PCC) within 48 hours of enrolment, or with known hypercoagulable state
7. Known inherited or acquired bleeding disorder. E.g. acquired storage pool deficiency; paraproteinaemia with platelet inhibition; known inherited or acquired prothrombotic disorders
9. Patients receiving anticoagulant therapy or anti-platelet therapy
10. Patients with overt disseminated intravascular coagulation
11. Patints with visible haematuria at time of randomisation
12. Patients requiring a platelet transfusion threshold >10x10 to the power of 9/L at time of randomisation
13. Patients with anuria (defined as urine output < 10mls/hr over 24 hours)
14. Patients who are pregnant
15. Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents
16. Allergic to tranexamic acid or epsilon amino caproic acid
17. Previously randomised in this study at any stage of their treatment

Recruitment start date

30/04/2015

Recruitment end date

30/08/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

John Radcliffe Hospital
National Blood Service – Oxford Centre Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

NHS Blood and Transplant (NHSBT)

Sponsor details

John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

NHS Blood and Transplant (NHSBT)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We plan to publish the protocol and the final results of the study

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes