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

Primary Purpose

Cancer of the Bone, Limb Salvage

Status

Recruiting

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Tranexamic Acid

0.9% sodium chloride

About this trial

This is an interventional supportive care trial for Cancer of the Bone focused on measuring Blood Transfusion, Cancer of the bone, Distal femur, Limb Salvage, Malignant Bone Tumor, Placebo, Proximal tibia, Randomized, Tranexamic acid, TXA

Eligibility Criteria

undefined - 24 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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 or 10x IULN for patients receiving HDMTX)
- 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.

Sites / Locations

St. Jude Children's Research HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tranexamic Acid

Placebo

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Difference in intra-operatively transfused blood volume (mL/kg)

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.

Difference in post-operatively transfused blood volume (mL/kg)

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

Changes in platelet level

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.

Changes in hemoglobin level (g/dL)

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.

Post-operative daily surgical drain output

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.

Changes in estimated blood loss (EBL)

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.

Intra-or post-operatively transfused blood volume

Regression model will be used to access the correlation between the log transformed intra-or post-operatively transfused blood volume and EBL.

Full Information

NCT ID

NCT04410042

First Posted

May 8, 2020

Last Updated

July 7, 2023

Sponsor

St. Jude Children's Research Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04410042

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 29, 2021 (Actual)

Primary Completion Date

September 2024 (Anticipated)

Study Completion Date

March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cancer of the Bone, Limb Salvage

Keywords

Blood Transfusion, Cancer of the bone, Distal femur, Limb Salvage, Malignant Bone Tumor, Placebo, Proximal tibia, Randomized, Tranexamic acid, TXA

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

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.

Allocation

Randomized

Enrollment

39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Tranexamic Acid

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tranexamic Acid

Other Intervention Name(s)

Cyklokapron®

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

0.9% sodium chloride

Other Intervention Name(s)

Salt water

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Difference in intra-operatively transfused blood volume (mL/kg)

Description

Time Frame

During surgery

Title

Difference in post-operatively transfused blood volume (mL/kg)

Description

Time Frame

After surgery; approximately 1-7 days

Secondary Outcome Measure Information:

Title

Changes in platelet level

Description

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)

Title

Changes in hemoglobin level (g/dL)

Description

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)

Title

Post-operative daily surgical drain output

Description

Time Frame

After surgery for the duration until the drain is pulled (approximately 1-7 days)

Title

Changes in estimated blood loss (EBL)

Description

Time Frame

During surgery until the conclusion of surgery

Title

Intra-or post-operatively transfused blood volume

Description

Regression model will be used to access the correlation between the log transformed intra-or post-operatively transfused blood volume and EBL.

Time Frame

During and after surgery (approximately 1-7 days)

10. Eligibility

Sex

All

Maximum Age & Unit of Time

24 Years

Accepts Healthy Volunteers

Eligibility 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: Upward trending peripheral absolute neutrophil count (ANC) 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 or 10x IULN for patients receiving HDMTX) 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michael D. Neel, MD

Phone

866-278-5833

referralinfo@stjude.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael D. Neel, MD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael D. Neel, MD

Phone

866-278-5833

referralinfo@stjude.org

First Name & Middle Initial & Last Name & Degree

Michael D. Neel, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing Time Frame

Data will be made available at the time of article publication.

IPD Sharing 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.

Links:

URL

http://www.stjude.org

Description

St. Jude Children's Research Hospital

URL

http://www.stjude.org/protocols

Description

ClinicalTrials Open at St. Jude

Learn more about this trial

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

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