American Trial Using Tranexamic Acid in Thrombocytopenia

NCT ID: NCT02578901

Last Updated: 2021-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 330 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2020-06-11

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.

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.

Conditions

Thrombocytopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Tranexamic Acid (TXA)

IV or PO administered after meeting inclusion/exclusion criteria

Group Type: ACTIVE_COMPARATOR

Tranexamic Acid

Intervention Type: DRUG

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

Placebo

IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

TXA; NS

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Susanne May

Professor, Biostatistics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Terry Gernsheimer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of North Carolina

Chapel Hill, North Carolina, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Washington

Seattle, Washington, United States

Countries

United States

References

Poston JN, Brown SP, Ilich A, Ginsburg AS, Herren H, El Kassar N, Jensen CE, Triulzi DJ, Key NS, May S, Gernsheimer TB. Fewer severe infections with tranexamic acid in patients with hematologic malignancies. Res Pract Thromb Haemost. 2024 Mar 1;8(2):102358. doi: 10.1016/j.rpth.2024.102358. eCollection 2024 Feb.

Reference Type: DERIVED

PMID: 38666065 (View on PubMed)

Ilich A, Gernsheimer TB, Triulzi DJ, Herren H, Brown SP, Holle LA, Lucas AT, de Laat B, El Kassar N, Wolberg AS, May S, Key NS. Absence of hyperfibrinolysis may explain lack of efficacy of tranexamic acid in hypoproliferative thrombocytopenia. Blood Adv. 2023 Mar 28;7(6):900-908. doi: 10.1182/bloodadvances.2022008255.

Reference Type: DERIVED

PMID: 36044391 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1U01HL122272-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00003329

Identifier Type: -

Identifier Source: org_study_id