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Tranexamic Acid Use to Reduce Blood Transfusion in Pediatric Cancer Patients Undergoing Limb Salvage Procedure

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ClinicalTrials.gov Identifier: NCT04410042
Recruitment Status : Not yet recruiting
First Posted : June 1, 2020
Last Update Posted : November 18, 2020
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief Summary:

This is a randomized double-blind control trial evaluating the use Tranexamic acid (TXA) to decrease blood loss and transfusion requirements in pediatric and young adult cancer patients undergoing a limb salvage procedure that frequently requires perioperative or post-operative transfusions of blood products.

Primary Objective

  • To evaluate the difference in intra-or post-operatively transfused blood volume (mL/kg) for patients undergoing limb salvage procedures of the distal femur or proximal tibia who are randomized to receive perioperative tranexamic acid (TXA) versus placebo.

Secondary Objectives

  • To evaluate changes in platelets and in hemoglobin from pre-op to post-op level for patients randomized to receive perioperative TXA versus placebo.
  • To evaluate differences in post-operative daily surgical drain output for patients randomized to receive perioperative TXA versus placebo.
  • To evaluate changes in estimated blood loss (EBL) for patients randomized to receive perioperative TXA versus placebo.
  • To evaluate the association between the intra-or post-operatively transfused blood volume and estimated blood loss (EBL) for patients randomized to receive perioperative TXA and placebo, respectively.

Exploratory Objectives

  • To evaluate differences in functional outcomes post-operatively for patients randomized to receive perioperative TXA versus placebo.
  • To explore if significant correlations are observed between parameters reported with rotational thromboelastometry (ROTEM®) and EBL and transfusion requirements in pediatric and young adult patients undergoing limb salvage procedure who are randomized to perioperative TXA versus placebo.
  • To evaluate differences in the prevalence and management of wound complications such as superficial or periprosthetic infections, wound dehiscence, contact dermatitis, post- operative hematomas, or any other clinically significant wound complication between patients randomized to receive perioperative TXA versus placebo.

Condition or disease Intervention/treatment Phase
Cancer of the Bone Limb Salvage Drug: Tranexamic Acid Other: 0.9% sodium chloride Phase 3

Detailed Description:

Eligible participants undergoing limb salvage procedures will be randomized to receive either tranexamic acid (TXA) or placebo peri-operatively.

The initial dose of tranexamic acid/placebo will be given at the initiation of surgical preparation. The second dose will be given 6 hours after the first dose (either intraoperatively or post-operatively). All doses will be given intravenously. Doses will be double blinded and randomized for each surgical procedure.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: To allow for the study team and participants to remain blinded to the treatment assignment, the study drug will be labeled as Tranexamic Acid/Placebo (TXAKIDS) followed by applicable dose and administration instructions.
Primary Purpose: Supportive Care
Official Title: Tranexamic Acid (TXA) to Reduce Volume Of Blood Transfused In Pediatric And Young Adult Cancer Patients Undergoing Limb Salvage Procedure Of A Lower Extremity
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tranexamic Acid
At initiation of surgical preparation, participants randomized to the active treatment arm will receive tranexamic acid 10 mg/kg (max 1 g), given via syringe pump programmed to infuse over 15 minutes. If no unacceptable toxicities occur, a second dose of tranexamic acid IV push over 5 to 15 minutes will be given 6 hours (with a window of +/- 30 minutes) after the first dose (either intra- or post-operatively).
Drug: Tranexamic Acid
Given IV
Other Name: Cyklokapron®

Placebo Comparator: Placebo
At initiation of surgical preparation, participants randomized to the placebo treatment arm will receive 0.9% sodium chloride (salt water). It will be matched in appearance, volume, and administration to the active treatment arm with tranexamic acid. If no unacceptable toxicities occur, a second dose of placebo IV push over 5 to 15 minutes will be given 6 hours (with a window of +/- 30 minutes) after the first dose (either intra- or post-operatively).
Other: 0.9% sodium chloride
Given IV
Other Name: Salt water




Primary Outcome Measures :
  1. Difference in intra-operatively transfused blood volume (mL/kg) [ Time Frame: During surgery ]
    The intra-operative volumes of transfused blood for both the TXA treated group and placebo group will be estimated with a two-sided 95% confidence interval. The blood volumes transfused per kilogram of body weight of the two groups (TXA vs. Placebo) will be evaluated using a two-sided student's t-test after log(1+x) transformation.

  2. Difference in post-operatively transfused blood volume (mL/kg) [ Time Frame: After surgery; approximately 1-7 days ]
    The post-operative volumes of transfused blood for both the TXA treated group and placebo group will be estimated with a two-sided 95% confidence interval. The blood volumes transfused per kilogram of body weight of the two groups (TXA vs. Placebo) will be evaluated using a two-sided student's t-test after log(1+x) transformation.


Secondary Outcome Measures :
  1. Changes in platelet level [ Time Frame: Pre-operatively (no more than 7 days prior to start of therapy), daily while inpatient and post operatively (approximately 1 week post-op) ]
    Summary statistics will be provided for the changes in platelet level from pre-op to post-op level, for both the TXA and placebo group. Two sample t-test or Wilcoxon rank sum test will be used to compare the differences between the two groups. Multiple comparison correction might be used for p-values to address the multiple testing issues due to measurements at multiple time points.

  2. Changes in hemoglobin level (g/dL) [ Time Frame: Pre-operatively (no more than 7 days prior to start of therapy), daily while inpatient and post operatively (approximately 1 week post-op) ]
    Summary statistics will be provided for the decline in hemoglobin from pre-op to post-op level, for both the TXA and placebo group. Two sample t-test or Wilcoxon rank sum test will be used to compare the differences between the two groups. Multiple comparison correction might be used for p-values to address the multiple testing issues due to measurements at multiple time points.

  3. Post-operative daily surgical drain output [ Time Frame: After surgery for the duration until the drain is pulled (approximately 1-7 days) ]
    Summary statistics will be provided for postoperative daily surgical drain output (in milliliters per 24 hour period for the duration of the drain) for each group. The group difference will be compared using two-sample t-test or Wilcoxon rank sum test depending on the distribution of the observed data. Multiple comparison correction might be used for p-values to address the multiple testing issues due to measurements at multiple time points.

  4. Changes in estimated blood loss (EBL) [ Time Frame: During surgery until the conclusion of surgery ]
    The EBL for pre-op to post-op level, for both the TXA treated group and placebo group will be estimated with a two-sided 95% confidence interval. The EBL of the two groups (TXA vs. Placebo) will be evaluated using a two-sample t-test or Wilcoxon rank sum test depending on the distribution of the observed data.

  5. Intra-or post-operatively transfused blood volume [ Time Frame: During and after surgery (approximately 1 -7 days) ]
    Regression model will be used to access the correlation between the log transformed intra-or post-operatively transfused blood volume and EBL.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant undergoing limb salvage procedure of malignant bone tumor of the distal femur or proximal tibia, which typically requires blood transfusions.
  • Patient under the age of 25
  • Adequate bone marrow function defined as:

    • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm^3
    • Platelet count ≥ 100,000/mm^3 (transfusion independent defined as no platelets required for 4 days)
    • Hemoglobin ≥ 8.0 g/dL
    • No RBC transfusion within 24 hours
  • Adequate renal function defined as:

    • Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73m^2 OR
    • Maximum serum creatinine based on age/gender as follows: Age 1 day to < 1 years: maximum serum creatinine (mg/dL) 0.6 for males and 0.5 for females; Age 1 to < 2 years: maximum serum creatinine (mg/dL) 0.6 for males and 0.6 for females; Age 2 to < 6 years: maximum serum creatinine (mg/dL) 0.8 for males and 0.8 for females; Age 6 to < 10 years: maximum serum creatinine (mg/dL) 1.0 for males and 1.0 for females; Age 10 to < 13 years: maximum serum creatinine (mg/dL) 1.2 for males and 1.2 for females; Age 13 to < 16 years: maximum serum creatinine (mg/dL) 1.5 for males and 1.4 for females; Age ≥ 16 years: maximum serum creatinine (mg/dL) 1.7 for males and 1.4 for females
  • Adequate liver function defined as:

    • Total bilirubin ≤ 1.5x the institutional upper limit of normal (IULN) for age
    • ALT (SGPT) and AST (SGOT) ≤ 2.5x IULN for age (or <5x IULN for patients with documented disease involving the liver)
    • Serum albumin > 2 g/dL
  • Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5
  • Female participants of child-bearing potential (>10 years old) must have a negative serum or urine pregnancy test within 72 hours of sedation

Exclusion Criteria:

  • Participants whose limb salvage procedure may require significant manipulation of major blood vessels.
  • Participants with known bone marrow deficiency resulting in red blood cell deficiency (e.g. Diamond-Blackfan anemia)
  • Participants receiving erythropoietin-stimulating agents (e.g. epoetin alfa)
  • Participants with active hemorrhagic cystitis (e.g. alkylator-induced) with gross hematuria or >50 RBCs per high powered field on urinalysis
  • Participants actively receiving all-trans retinoic acid (ATRA) or isotretinoin (Accutane)
  • Participants with known allergies to antifibrinolytics
  • Participants with known hypercoagulopathies
  • Personal history of a thrombosis or active thrombus
  • Participants currently on anticoagulation medications (e.g. warfarin, enoxaparin)
  • Participants with a history of seizures. Patients with a history of febrile seizure are eligible.
  • Persisting toxicity related to other systemic therapies (e.g. chemotherapy) which constitutes an unacceptable safety risk based on the judgment of the PI and/or the primary treating physician.
  • Female participants who are currently pregnant or actively breastfeeding.
  • Female participants who are currently receiving estrogen-based contraception therapy.
  • Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
  • Participants enrolled in another clinical trial utilizing an IND/IDE experimental therapy.
  • Participants with a history of CNS disease.
  • Participants with known bleeding disorder.
  • Participants with known platelet dysfunction.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04410042


Contacts
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Contact: Michael D. Neel, MD 866-278-5833 referralinfo@stjude.org

Locations
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United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Contact: Michael D. Neel, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Michael D. Neel, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
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Principal Investigator: Michael D. Neel, MD St. Jude Children's Research Hospital
Additional Information:
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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT04410042    
Other Study ID Numbers: TXAKIDS
NCI-2020-02984 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: June 1, 2020    Key Record Dates
Last Update Posted: November 18, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data will be made available at the time of article publication.
Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Jude Children's Research Hospital:
Blood Transfusion
Cancer of the bone
Distal femur
Limb Salvage
Malignant Bone Tumor
Placebo
Proximal tibia
Randomized
Tranexamic acid
TXA
Additional relevant MeSH terms:
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Bone Neoplasms
Neoplasms by Site
Neoplasms
Bone Diseases
Musculoskeletal Diseases
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants