TRial to EvaluAte Tranexamic Acid Therapy in Thrombocytopenia (TREATT)

NHS Blood and Transplant

Status and phase: Completed; Phase 3

Conditions: Hematologic Neoplasms; Hemorrhage; Hematopoietic Stem Cell Transplantation

Treatments: Drug: Tranexamic acid (TXA).; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03136445

ISRCTN73545489 (Registry Identifier)

12-01-CSU

2014-001513-35 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 616 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 ≤10x10⁹/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 >10x10/⁹L 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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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616 participants in 2 patient groups, including a placebo group

Intervention Arm

Experimental group

Description:

Tranexamic acid (TXA). Dose schedule TXA 1g every eight hours IV or 1.5g every eight hours PO.

Treatment:

Drug: Tranexamic acid (TXA).

Control Arm

Placebo Comparator group

Description:

Placebo (saline) if administration is IV. Placebo tablet matched for appearance to TXA if oral.

Treatment:

Drug: Placebo