Does Early Administration of Tranexamic Acid Reduce Blood Loss and Perioperative Transfusion Requirement

• ClinicalTrials.gov Identifier: NCT03182751
• Recruitment Status: Recruiting
• First Posted: June 9, 2017
• Last Update Posted: October 29, 2020
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Brandon James Yuan, Mayo Clinic

Study Description

Brief Summary:

A single-center, prospective randomized study. Consecutive patients presenting with intertrochanteric hip fractures will be treated with tranexamic acid. Treatment will be initiated in the emergency department according to a previously studied protocol for trauma patients.

Condition or disease	Intervention/treatment	Phase
Hip Fractures	Drug: Tranexamic Acid (TXA); Drug: Placebo	Phase 2

Detailed Description:

The use of TXA in orthopedic trauma patients is an area of current research interest. A 2010 prospective randomized, controlled trial of perioperative TXA demonstrated reduction in transfusion requirements for intertrochanteric hip fractures treated with short, cephalomedullary nails. This was clinically, though not statistically, significant. Investigators recently conducted a randomized, controlled trial at this institution to evaluated the use of TXA in patients with femoral neck fractures treated with hemiarthroplasty or total hip arthroplasty and found clinically, albeit not statistically, significant reduction in transfusion requirement (accepted for publication). Perhaps tempering the effect seen with perioperative administration of TXA is the blood loss that occurs prior to surgery, the so-called "hidden" blood loss that can be as substantial as 1/3 of total blood loss from a hip fracture. This raises the question whether administration of tranexamic acid at the time of initial presentation after fracture could improve the perioperative care of these patients by decreasing the proportion of patients requiring transfusion and decreasing total blood loss.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects will be randomized into one of two study groups: TXA administration (treatment) or placebo (control). In order to ensure balance on the subject demographics between the two study groups, the subjects will be stratified on gender, age group (<75 vs. ≥75) and body mass index (<30 vs. ≥30). Within each stratum, subjects will be assigned to either the treatment group or control group using an electronic dynamic allocation program housed in a computer application developed by personnel in the Division of Biomedical Statistics and Informatics.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Using dynamic allocation will ensure that the study subjects will remain balanced on the stratification factors and the treatment group assignment throughout the entire subject accrual phase. This system will be utilized by Central pharmacy personnel to generate the treatment group assignments. Medications will then be delivered from the Central Pharmacy to the emergency department in packaging that does not delineate whether it contains placebo or tranexamic acid. Thus, the patient, treating surgeon, emergency department physician, residents, hospitalist group, anesthesiologist, and data collectors will remain blinded to the treatment assignment.
• Primary Purpose: Treatment
• Official Title: Does Early Administration of Tranexamic Acid Reduce Blood Loss and Perioperative Transfusion Requirement in Low Energy Hip Fracture Patients?
• Actual Study Start Date: April 2, 2018
• Estimated Primary Completion Date: October 1, 2021
• Estimated Study Completion Date: October 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Tranexamic Acid Arm (TXA); TXA will be administered intravenously via bolus dose of 1g over ten minutes and an additional 1g over the subsequent 8 hours.	Drug: Tranexamic Acid (TXA); The cohort of patients treated with early administration of TXA in the Emergency Department will be compared to a control group who were not treated with TXA at any point.; Other Name: Cyklokapron
Placebo Comparator: Control Arm; Patients in the control group will receive a placebo medication in the Emergency Department. Neither group will receive perioperative bolus dosing of TXA.	Drug: Placebo; The cohort of patients treated with a placebo in the Emergency Department will be compared to the active comparator group that will receive early administration of Tranexamic Acid.

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients transfused at least 1 unit of packed red blood cells [ Time Frame: Length of hospitalization; average stay is 3 to 5 days. ]
   Transfusion will be considered for all patients with hemoglobin values of less than 8 g/dL with persistent symptoms or history of significant cardiac disease that may render the patient less able to compensate for significant anemia. Blood transfusion will be considered in all patients with hemoglobin less than 7 g/dL, regardless of symptoms.

Secondary Outcome Measures :

1. Mean number of units transfused per patient [ Time Frame: Length of hospitalization; average stay is 3 to 5 days. ]
   Number of units of packed red blood cells per patient
2. Calculated blood loss [ Time Frame: Length of hospitalization; average stay is 3 to 5 days ]
   Calculated blood loss per patient
3. Incidence of symptomatic Venous Thromboembolism (VTE) [ Time Frame: Within 6 months of surgery ]
   Patients diagnosed with Venous Thromboembolism
4. Wound complications [ Time Frame: Within 6 months of surgery ]
   Any patient diagnosed with a wound complication
5. (Myocardial Infarction) MI diagnosed [ Time Frame: Within 6 months of surgery ]
   Any patient diagnosed with a myocardial infarction
6. Cerebrovascular accident (CVA) diagnosed [ Time Frame: Within 6 months of surgery ]
   Any patient diagnosed with a cerebrovascular accident
7. All-cause mortality [ Time Frame: At 6 months after surgery ]
   Any patient who suffers mortality

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• AO/OTA fracture classification 31A
• Surgically treated with sliding hip screw or cephalomedullary nail (short or long)
• Low energy, isolated injury
• Age greater than 18 years old

Exclusion Criteria:

• Intracapsular hip fractures: AO/OTA fracture classification 31B-C
• Polytrauma patients
• Creatinine clearance less than 30 mL/min
• History of unprovoked VTE and/or recurrent VTE
• Known history of Factor V Leiden, protein C/S deficiency, prothrombin gene mutation, anti-thrombin deficiency, anti-phospholipid antibody syndrome, lupus anticoagulant
• Pregnancy or breastfeeding (pregnancy tests will be performed on all patients of child-bearing potential)
• History of CVA, MI, or VTE within the previous 30 days
• Coronary stent placement within the previous 6 months
• Disseminated intravascular coagulation
• Intracranial hemorrhage

Contacts and Locations

Contacts

Contact: Chelsea Boe, MD; (507) 284-1175; boe.chelsea@mayo.edu

Contact: Elsa C Chase, MBA; 507-284-5445; chase.elsa@mayo.edu

Locations

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Chelsea Boe, MD 507-284-1175 boe.chelsea@mayo.edu

Principal Investigator: Brandon Yuan, MD

Sponsors and Collaborators

Mayo Clinic

Investigators

• Principal Investigator: Brandon Yuan, MD; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Brandon James Yuan, Assistant Professor, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03182751
• Other Study ID Numbers: 16-004988
• First Posted: June 9, 2017
• Last Update Posted: October 29, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: We do not plan to share IPD with other researchers that are outside of the primary listed researchers within the primary institution where the investigation is being performed. While we intend the share the overall results of the study through peer review, we do not have our institution's IRB approval to share individual participant data outside of the institution.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Hip Fractures; Fractures, Bone; Wounds and Injuries; Femoral Fractures; Hip Injuries; Leg Injuries; Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants