American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT)

American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT)

The purpose of this study is to evaluate the usefulness of antifibrinolytic therapy with tranexamic acid (TXA) in preventing bleeding in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy.

Study Overview

• Status: Completed
• Conditions: Thrombocytopenia
• Intervention / Treatment: Drug: Tranexamic Acid; Drug: Placebo

Detailed Description

The purpose of this study is to conduct a prospective, randomized, blinded, placebo controlled trial to evaluate the usefulness of antifibrinolytic therapy with tranexamic acid in preventing bleeding in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy. The results of this study will change practice by providing evidence as to whether or not TXA is effective and safe treatment when used as an adjunct to platelet transfusion therapy in the thrombocytopenic patient.

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 21599
      • University of North Carolina
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria (all must be met):

• Must be ≥ 18 years of age
• Confirmed diagnosis of a hematologic malignancy or aplasia
• Undergoing or planned chemotherapy, immunotherapy, or hematopoietic stem cell transplantation
• Anticipated to have hypoproliferative thrombocytopenia resulting in a platelet count of ≤ 10,000/microliters for ≥ 5 days
• Able to provide informed consent and comply with treatment and monitoring, or having a Legally Authorized Representative (LAR)

Exclusion criteria (none can be present):

• Diagnosis of acute promyelocytic leukemia undergoing induction chemotherapy
• History of ITP, TTP or HUS
• Subjects receiving L-asparaginase as part of their current cycle of treatment
• Subjects with a past history or current diagnosis of arterial or venous thromboembolic disease including acute coronary syndrome, peripheral vascular disease and retinal arterial or venous thrombosis (except when a prior history of central line thrombosis has resolved)
• Subjects with a diagnosis/previous history of sinusoidal obstruction syndrome (also called veno-occlusive disease)
• Subjects receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex Concentrates (PCC) and/or an antifibrinolytic agent within 48 hours of enrollment, or with known hypercoagulable state

• Known inherited or acquired bleeding disorder including, but not limited to:

  • Acquired storage pool deficiency
  • Paraproteinemia with platelet inhibition
• Known inherited or acquired prothrombotic disorders, including antiphospholipid syndrome. Those with lupus anticoagulant or positive antiphospholipid serology without thrombosis are not excluded.
• Subjects receiving anticoagulant therapy or anti-platelet therapy (except when receiving prophylactic anticoagulant or low dose aspirin therapy for prophylaxis only with a plan to discontinue when the platelet count falls below 50,000)
• Patients with DIC according to the patient's physician
• Subjects with WHO Grade 2 bleeding or greater within 48 hours prior to activation
• Subjects requiring a platelet transfusion threshold > 10,000/microliters at time of randomization
• Subjects with anuria (defined as urine output < 10mls/hr over 24 hours)
• Subjects on dialysis
• Subjects with creatinine ≥5.7mg/dL
• Subjects who are pregnant or nursing or unwilling to use contraception during and for 30 days after taking the study drug (both males and females)
• Subjects enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents.
• Known allergy to tranexamic acid
• Having been previously randomized in this study at any stage of their treatment
• Subjects who are unwilling to accept blood or blood component transfusions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tranexamic Acid (TXA); IV or PO administered after meeting inclusion/exclusion criteria	Drug: Tranexamic Acid; Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered; Other Names: TXA
Placebo Comparator: Placebo; IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria	Drug: Placebo; Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered; Other Names: NS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding Within 30 Days	Proportion of patients with bleeding of WHO grade 2 or above, over the study period of 30 days after activation of study drug.	30 days after activation of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Platelet Transfusions	Number of platelet transfusions per patient during the first 30 days post prescription activation of study drug	30 days after activation of study drug
Number of Days Alive and Without WHO Grade 2 Bleeding	Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug	during the first 30 days post activation of study drug

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): June 11, 2020

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 15, 2015
• First Posted (Estimate): October 19, 2015

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: February 26, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Tranexamic Acid; Thrombocytopenia; TXA; Chemotherapy induced thrombocytopenia
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: STUDY00003329; 1U01HL122272-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized public data set will be available after publication of primary results
• IPD Sharing Time Frame: Public use data will be available within 3 years after primary outcome completion. These will be available through NHLBI and the duration of their availability will be according to NHLBI biolincc protocols.
• IPD Sharing Access Criteria: The access criteria will be according to NHLBI biolincc protocols at the time of the request.