TRial to EvaluAte Tranexamic Acid Therapy in Thrombocytopenia

Hemorrhage Clinical Trial

— TREATT  

Official title:

A Double-blind, Randomised Controlled Trial Evaluating the Safety and Efficacy of Antifibrinolytics (Tranexamic Acid) in Patients With Haematological Malignancies With Severe Thrombocytopenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03136445
• Other study ID #: 12-01-CSU
• Secondary ID: 2014-001513-35IS
• Status: Completed
• Phase: Phase 3
• Start date: June 2015
• Est. completion date: June 18, 2022

Study information

• Verified date: November 2023
• Source: NHS Blood and Transplant
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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. The investigators will measure the rates of bleeding daily using a short structured assessment of bleeding and will record the number of transfusions given to patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 616
• Est. completion date: June 18, 2022
• Est. primary completion date: February 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients are eligible for this trial if:

1. Aged =18 years of age

2. Confirmed diagnosis of a haematological malignancy

3. Undergoing chemotherapy, or chemotherapy is planned, or haematopoietic stem cell transplantation

4. Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of =10x10?/L for = 5 days

5. Able to comply with treatment and monitoring

Exclusion Criteria:

A patient will not be eligible for this trial if he/she fulfils one or more of the following criteria:

1. 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.

2. Diagnosis of acute promyelocytic leukaemia (APML) and undergoing induction chemotherapy

3. Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome)

4. Patients with known inherited or acquired prothrombotic disorders e.g.

1. Lupus anticoagulant

2. Positive antiphospholipids

5. 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

6. Patients receiving L-asparaginase as part of their current cycle of treatment

7. History of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS)

8. Patients with overt disseminated intravascular coagulation (DIC) (See Appendix 3 in the protocol for definition)

9. Patients requiring a platelet transfusion threshold >10x10/?L at time of randomisation. (This refers to patients who require their platelet count to be maintained at a certain specified level on an ongoing basis, and excludes a transient rise in the threshold due to sepsis.)

10. Patients with a known inherited or acquired bleeding disorder e.g.

1. Acquired storage pool deficiency

2. Paraproteinaemia with platelet inhibition

11. Patients receiving anticoagulant therapy or anti-platelet therapy

12. Patients with visible haematuria at time of randomisation

13. Patients with anuria (defined as urine output < 10 mls/hr over 24 hours).

14. Patients with severe renal impairment (eGFR =30 ml/min/1.73m²)

15. Patients with a previous history of epilepsy, convulsions, fits or seizures

16. Patients who are pregnant or breast-feeding

17. Allergic to tranexamic acid.

18. Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents.

19. Patients previously randomised into this trial at any stage of their treatment.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematopoietic Stem Cell Transplantation
• Hemorrhage
• Thrombocytopenia

Intervention

Drug:
• Tranexamic acid (TXA).
IV or oral preparation. IV tranexamic acid or Oral tablet of tranexamic acid.
• Placebo
IV (saline) or oral placebo tablets

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Royal Brisbane	Brisbane
Australia	Canberra Hospital	Canberra
Australia	Andrew Love Cancer Centre	Geelong
Australia	Alfred Hospital	Melbourne
Australia	Monash Health	Melbourne
Australia	St Vincent's Hospital	Melbourne
Australia	Victorian Comprehensive Cancer Centre	Melbourne
Australia	Royal North Shore Hospital	St Leonards
Australia	St Vincent's Hospital	Sydney
Australia	Westmead Hospital	Westmead
United Kingdom	Royal United Hospital	Bath
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Heartlands Hospital	Birmingham
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Royal Devon and Exeter Hospital	Exeter
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	St James's Hospital	Leeds
United Kingdom	Lincoln County Hospital	Lincoln
United Kingdom	King's College Hospital	London
United Kingdom	University College London Hospitals	London
United Kingdom	Freeman Hospital	Newcastle
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Salisbury District Hospital	Salisbury

Sponsors (3)

Lead Sponsor	Collaborator
NHS Blood and Transplant	Monash University, National Health and Medical Research Council, Australia

Countries where clinical trial is conducted

Australia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of days with thrombocytopenia (=10x10?/L, =30x10?L, =50x10?/L).	Measured by number of days that the patient's laboratory results indicate that the patient is thrombocytopenic.	Measured during first 30 days from first dose of IMP.
Other	Reasons for platelet and red cell transfusions.	Reasons for platelet and red cell transfusions as documented by clinician.	Measured during first 30 days from first dose of IMP.
Other	Proportion of days with fever	Highest daily temperature = 38.1°C	Measured during first 30 days from first dose of IMP.
Primary	The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment.	The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment.; 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.	The first 30 days from first dose of trial treatment
Secondary	Proportion of days with bleeding (WHO grade 2 or above) up to Study Day 30.	Number of days where WHO grade 2 or above bleeding has been recorded bleeding using WHO bleeding criteria.	The first 30 days from first dose of trial treatment .
Secondary	Time to first episode of bleeding of WHO grade 2 or greater up to study day 30.	Bleeding assessed using WHO bleeding criteria.	The first 30 days from first dose of trial treatment.
Secondary	Highest grade of bleeding a patient experiences up to study day 30.	Measured using WHO bleeding criteria.	The first 30 days from first dose of trial treatment.
Secondary	Number of platelet transfusions per patient up to study day 30.	Measured by number of recorded platelet transfusions per patient.	The first 30 days from first dose of trial treatment.
Secondary	Number of red cell transfusions per patient up to study day 30.	Measured by number of recorded red cell transfusions per patient.	The first 30 days from first dose of trial treatment.
Secondary	Proportion of patients surviving at least 30 days without a platelet transfusion.	Measured by calculating number of patients surviving at least 30 days without a platelet transfusion.	The first 30 days from first dose of trial treatment.
Secondary	Proportion of patients surviving at least 30 days without a red cell transfusion.	Measured by calculating the number of patients surviving at least 30 days without a red cell transfusion.	The first 30 days from first dose of trial treatment.
Secondary	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.	Measured by calculating number of clinically diagnosed thrombotic events from Treatment Day 1 i.e the first day that the investigational medicinal product (IMP) is administered, up to and including the next 120 days.	Up to and including 120 days from the first administration of investigational medicinal product (IMP).
Secondary	Number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of first administration of trial treatment.	Measured by calculating number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of Treatment Day 1 i.e the first day that the IMP is administered.	Up to and including 60 days from the first administration of IMP.
Secondary	All-cause mortality during the first 30 days and 120 days after the first dose of trial treatment is administered. All-cause mortality during the first 30 days and 120 days after the first dose of trial treatment is administered	Measured by calculating number of deaths in first 30 days and 120 days after Treatment Day 1 i.e the first day that the IMP is administered.	Up to and including 120 days from the first administration of IMP.
Secondary	Death due to thrombosis during the first 120 days after the first dose of trial treatment is administered.	Measured by calculating number of deaths due to thrombosis during the first 120 days after Treatment Day 1 i.e the first day that the IMP is administered.	Up to and including 120 days from the first administration of IMP.
Secondary	Death due to bleeding during the first 30 days after the first dose of trial treatment is administered.	Measured by calculating number of deaths due to bleeding during the first 30 days	Up to and including 30 days from the first administration of IMP.
Secondary	Number of serious adverse events (SAE) from first administration of trial treatment until 60 days after the first dose of trial treatment is administered.	Measured by calculating the total number of SAE's reported from first administration of IMP.	Up to and including 60 days from the first administration of IMP.