Clinical trial NCT03806556: A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia
Official title: A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Pediatric Cancer
Thrombocytopenia
Hemostatic Disorder
Coagulation Defect; Acquired
Keywords: tranexamic acid
anti-fibrinolytic agents
chemotherapy-induced thrombocytopenia
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2019-01-16
Enrollment: 11
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial is designed as a prospective, randomized, controlled, blinded (patient, caregiver, physician, assessor) trial with two parallel groups and a primary endpoint of feasibility and safety. Randomization will be performed as block randomization with a 1:1 allocation within blocks of size four.
Primary purpose: PREVENTION

Brief summary: This study evaluates the use of tranexamic acid (TXA) in addition to standard therapy in children receiving chemotherapy or blood and/or marrow transplantation to decrease the risk of bleeding. Half of participants will receive tranexamic acid and half of participants will receive placebo.

Detailed description: The purpose of this study is to conduct a prospective, randomized, blinded, placebo controlled trial to evaluate the safety and feasibility of the addition of antifibrinolytic therapy with tranexamic acid to the standard care in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy in order to prevent bleeding. 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.

Eligibility criteria: Inclusion Criteria:

* Patients must have a confirmed diagnosis of hematologic malignancy or solid tumor malignancy
* Patients must be undergoing or planned chemotherapy or BMT
* Patients will only be eligible to receive study drug or placebo during inpatient periods
* Patients must be predicted to have thrombocytopenia ≤20,000/microliter (uL) for ≥5 days
* Patient must have a platelet transfusion threshold of ≤30,000/uL
* Patients must be \>14 days beyond their last dose of Pegylated(PEG)-Asparaginase or \>72 hours beyond their last dose of Erwinia Asparaginase
* Patients must be able to comply with treatment and monitoring

Exclusion Criteria:

* Diagnosis of acute promyelocytic leukemia (APL)
* History of Immune Thrombocytopenic Purpura (ITP), Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS)
* Diagnosis of Disseminated Intravascular Coagulopathy (DIC)
* History of inherited or acquired bleeding disorder AND/OR inherited or acquired prothrombotic disorder
* Patient must not have WHO Grade 2 bleeding or greater within 48 hours prior to enrollment or study drug activation
* Patient must not have received PEG-Asparaginase within the 7 day period prior to enrollment. If given within the 8-14 day period prior to enrollment patients are eligible if prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR) and fibrinogen are obtained and are within 1.5 times the upper limits of normal.
* Patient must not be receiving tranexamic acid or other anti-fibrinolytic agent or any other agent to promote hemostasis (which includes DDAVP, recombinant Factor VII, Prothrombin Complex Concentrate, Estrogen Derivatives and Progestins)
* Patient must not be receiving therapy with anticoagulation or antiplatelet therapy (which includes heparin infusion, enoxaparin, aspirin. If anticoagulant/antiplatelet therapy is discontinued when platelet count is \<50,000/uL patient will be eligible for enrollment)
* Patient must not be receiving platelet growth factors
* Current thromboembolic event
* History of thromboembolic event \<6 months prior to enrollment
* Current/prior history of sinusoidal obstruction disease
* Visible hematuria
* Renal dysfunction (as defined by age-specific creatinine values calculated by Schwartz equation) or hemodialysis or anuria (defined as \<10 mL urine/hour over 24 hours)
* History of seizures
* Allergy to tranexamic acid
* Pregnancy
* Unwilling to accept blood product transfusions

Primary outcomes:
measure: Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03
timeFrame: From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
measure: Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited
timeFrame: From time of recruitment of the first patient until the last patient is enrolled, up to 16 months in duration
Secondary outcomes:
measure: World Health Organization (WHO) Bleeding Scale Grade 2 or Higher Bleeding
timeFrame: 30 days after activation of study drug
measure: Number of Platelet and Red Blood Cell Transfusions
timeFrame: 30 days after activation of study drug
measure: Number of Days Alive and Without WHO Grade 2 Bleeding or Greater
timeFrame: 30 days after activation of study drug
measure: The Occurrence of Thromboembolic Adverse Events and Serious Adverse Events
timeFrame: From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
measure: Bleeding of Any Grade
timeFrame: From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
measure: Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period
timeFrame: From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Childrens Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: UPMC Childrens Hospital of Pittsburgh
name: Meghan McCormick, MD
role: PRINCIPAL_INVESTIGATOR
References: