Back to resultsA Pediatric Trial Using Tranexamic Acid in Thrombocytopenia
Primary Purpose
Pediatric Cancer, Thrombocytopenia, Hemostatic Disorder
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tranexamic Acid
Normal saline
Sponsored by
About this trial
This is an interventional prevention trial for Pediatric Cancer focused on measuring tranexamic acid, anti-fibrinolytic agents, chemotherapy-induced thrombocytopenia
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
Sites / Locations
- UPMC Childrens Hospital of Pittsburgh
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tranexamic Acid
Placebo
Arm Description
Doses will be given intravenous (IV). Doses are administered every 8 hours or three times daily (TID) per the discretion of the treating investigator. TXA dose will be 10mg/kg, diluted in normal saline to a total volume of 15 milliliters (mL).
Doses will be given intravenous (IV). Doses are administered every 8 hours or TID per the discretion of the treating investigator. Normal saline will be administered at a total volume of 15mL.
Outcomes
Primary Outcome Measures
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
Adverse Events and Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study and up to 30 days following discontinuation of the study drug, regardless of attribution. Adverse events and serious adverse events will be tabulated by type and grade according to the NCI CTCAE v 4.03.
The hypothesis is that tranexamic acid can be safely added to standard care regimens in patients with hematologic malignancies or solid tumors during periods of severe thrombocytopenia. Analysis limited to a descriptive assessment of the safety of tranexamic acid in patients with hematologic malignancies or solid tumors by reported adverse events, serious adverse events and death.
Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited
Number of participants eligible for study enrollment and recruited.
The hypothesis is that tranexamic acid can be safely added to standard care regimens in patients with hematologic malignancies or solid tumors during periods of severe thrombocytopenia. A descriptive assessment of feasibility of recruitment by monitoring number of patients screened, number of patients eligible for enrollment and rate of recruitment (both start-up and ongoing) during study period to be completed by collecting data on the number of patients screened, the number of patients eligible for study inclusion, the number of eligible patients who consent to study inclusion and the number of consented patients activated to the study drug, organized in visual form by CONSORT diagram.
Secondary Outcome Measures
World Health Organization (WHO) Bleeding Scale Grade 2 or Higher Bleeding
Proportion of patients with bleeding of WHO grade 2 or above, after activation of study drug. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
Number of Platelet and Red Blood Cell Transfusions
Number of platelet and red blood cell transfusions per patient during the first 30 days post prescription activation of study drug
Number of Days Alive and Without WHO Grade 2 Bleeding or Greater
Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
The Occurrence of Thromboembolic Adverse Events and Serious Adverse Events
Any venous or arterial thrombosis on standard diagnostic imaging post-randomization
Bleeding of Any Grade
Proportion of patients with bleeding of any grade as assessed by WHO bleeding score, after activation of study drug
Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period
Highest grade of bleeding (as measured on WHO bleeding scale) during study period in each enrolled patient. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03806556
Brief Title
A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia
Official Title
A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
Low accrual rate, strategic reasons
Study Start Date
April 22, 2019 (Actual)
Primary Completion Date
August 25, 2020 (Actual)
Study Completion Date
August 25, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Meghan McCormick
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pediatric Cancer, Thrombocytopenia, Hemostatic Disorder, Coagulation Defect; Acquired
Keywords
tranexamic acid, anti-fibrinolytic agents, chemotherapy-induced thrombocytopenia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The investigational pharmacy will be notified when patients enroll on trial. When participants meet criteria for randomization, this will be completed by the Investigational Pharmacy. The pharmacy will prepare and distribute to floor nursing staff all doses of tranexamic acid (available in IV form as a colorless liquid) or placebo (as an equal volume of normal saline). Labels will not carry identifiers of which study arm the enrolled patient is on.
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tranexamic Acid
Arm Type
Experimental
Arm Description
Doses will be given intravenous (IV). Doses are administered every 8 hours or three times daily (TID) per the discretion of the treating investigator. TXA dose will be 10mg/kg, diluted in normal saline to a total volume of 15 milliliters (mL).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Doses will be given intravenous (IV). Doses are administered every 8 hours or TID per the discretion of the treating investigator. Normal saline will be administered at a total volume of 15mL.
Intervention Type
Drug
Intervention Name(s)
Tranexamic Acid
Other Intervention Name(s)
TXA
Intervention Description
IV medication administered after patient meets inclusion/exclusion criteria
Intervention Type
Drug
Intervention Name(s)
Normal saline
Other Intervention Name(s)
NS
Intervention Description
IV medication administered after patient meets inclusion/exclusion criteria
Primary Outcome Measure Information:
Title
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
Description
Adverse Events and Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study and up to 30 days following discontinuation of the study drug, regardless of attribution. Adverse events and serious adverse events will be tabulated by type and grade according to the NCI CTCAE v 4.03.
The hypothesis is that tranexamic acid can be safely added to standard care regimens in patients with hematologic malignancies or solid tumors during periods of severe thrombocytopenia. Analysis limited to a descriptive assessment of the safety of tranexamic acid in patients with hematologic malignancies or solid tumors by reported adverse events, serious adverse events and death.
Time Frame
From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
Title
Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited
Description
Number of participants eligible for study enrollment and recruited.
The hypothesis is that tranexamic acid can be safely added to standard care regimens in patients with hematologic malignancies or solid tumors during periods of severe thrombocytopenia. A descriptive assessment of feasibility of recruitment by monitoring number of patients screened, number of patients eligible for enrollment and rate of recruitment (both start-up and ongoing) during study period to be completed by collecting data on the number of patients screened, the number of patients eligible for study inclusion, the number of eligible patients who consent to study inclusion and the number of consented patients activated to the study drug, organized in visual form by CONSORT diagram.
Time Frame
From time of recruitment of the first patient until the last patient is enrolled, up to 16 months in duration
Secondary Outcome Measure Information:
Title
World Health Organization (WHO) Bleeding Scale Grade 2 or Higher Bleeding
Description
Proportion of patients with bleeding of WHO grade 2 or above, after activation of study drug. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
Time Frame
30 days after activation of study drug
Title
Number of Platelet and Red Blood Cell Transfusions
Description
Number of platelet and red blood cell transfusions per patient during the first 30 days post prescription activation of study drug
Time Frame
30 days after activation of study drug
Title
Number of Days Alive and Without WHO Grade 2 Bleeding or Greater
Description
Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
Time Frame
30 days after activation of study drug
Title
The Occurrence of Thromboembolic Adverse Events and Serious Adverse Events
Description
Any venous or arterial thrombosis on standard diagnostic imaging post-randomization
Time Frame
From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
Title
Bleeding of Any Grade
Description
Proportion of patients with bleeding of any grade as assessed by WHO bleeding score, after activation of study drug
Time Frame
From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
Title
Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period
Description
Highest grade of bleeding (as measured on WHO bleeding scale) during study period in each enrolled patient. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
Time Frame
From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meghan McCormick, MD
Organizational Affiliation
UPMC Childrens Hospital of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
UPMC Childrens Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized public data set will be available after publication of primary results
IPD Sharing Time Frame
Beginning within 1 year and ending 5 years after trial completion
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal may request data. Proposals should be directed to meghan.mccormick3@chp.edu. To gain access data requestors will need to sign a data access agreement.
Learn more about this trial
A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia
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