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

• ClinicalTrials.gov Identifier: NCT02578901
• Recruitment Status: Recruiting
• First Posted: October 19, 2015
• Last Update Posted: January 1, 2019
• Sponsor: University of Washington
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Susanne May, University of Washington

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Thrombocytopenia	Drug: Tranexamic Acid; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT)
• Study Start Date: June 2016
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: June 2020

Arms and Interventions

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 Name: 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 Name: NS

Outcome Measures

Primary Outcome Measures :

1. Bleeding within 30 days [ Time Frame: 30 days after activation of study drug ]
   Proportion of patients with bleeding of WHO grade 2 or above, over the study period of 30 days after activation of study drug.

Secondary Outcome Measures :

1. Number of platelet transfusions [ Time Frame: 30 days after activation of study drug ]
   Number of platelet transfusions per patient during the first 30 days post prescription activation of study drug
2. Number of days alive and without WHO grade 2 bleeding [ Time Frame: during the first 30 days post activation of study drug ]
   Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Heather Herren; 800-332-0586; hherren@uw.edu

Locations

United States, North Carolina

University of North Carolina; Recruiting

Chapel Hill, North Carolina, United States, 21599

Contact: Nigel Key, MD nigel_key@med.unc.edu

United States, Pennsylvania

University of Pittsburgh; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contact: Darrell Triulzi, MD Dtriulzi@itxm.org

United States, Washington

University of Washington; Recruiting

Seattle, Washington, United States, 98195

Contact: Terry Gernsheimer, MD bldbuddy@u.washington.edu

Sponsors and Collaborators

University of Washington

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Terry Gernsheimer, MD; University of Washington

More Information

• Responsible Party: Susanne May, Professor, Biostatistics, University of Washington
• ClinicalTrials.gov Identifier: NCT02578901 History of Changes
• Other Study ID Numbers: STUDY00003329; 1U01HL122272-01A1 ( U.S. NIH Grant/Contract )
• First Posted: October 19, 2015
• Last Update Posted: January 1, 2019
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized public data set will be available after publication of primary results
• 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.
• Access Criteria: The access criteria will be according to NHLBI biolincc protocols at the time of the request.
• URL: https://biolincc.nhlbi.nih.gov/home/

Keywords provided by Susanne May, University of Washington:

Thrombocytopenia; Tranexamic Acid; TXA; Chemotherapy induced thrombocytopenia

Additional relevant MeSH terms:

Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants