Bleeding, Craniosynostosis
Conditions
Keywords
antifibrinolytic, tranexamic acid
Brief summary
This is a randomized, blinded, prospective study that will investigate the potential benefit of tranexamic acid to reduce the intraoperative bleeding and blood transfusions in pediatric patients undergoing craniofacial surgeries.
Detailed description
Surgical procedures for the correction of craniofacial deformities result in unavoidable and significant blood loss in small children and infants. Patients may experience blood losses that exceed one to two blood volumes. In an effort to reduce our transfusion requirements, we have introduced tranexamic acid into our practice. However, the benefit of tranexamic acid in pediatric craniofacial surgery has not yet been reported. We hypothesize that the intraoperative use of tranexamic acid in pediatric patients presenting for craniofacial reconstructions will reduce blood loss and allogeneic transfusion requirements. This is a randomized, blinded, prospective study that will investigate the potential benefit of tranexamic acid to reduce the intraoperative bleeding and blood transfusions in pediatric patients undergoing craniofacial surgeries. An initial dose of 100 mg/kg tranexamic acid (Cyclokapron 100mg/ml) or an equal volume of a placebo will be administered over 15 minutes after the induction of anesthesia and before the skin incision. A maintenance infusion of 10 mg/kg/hr of tranexamic acid or equal volume of a placebo will be started upon completion of the initial dose and will be continued until skin closure. The primary outcome will include the reduction in the total volume of allogeneic erythrocytes.
Interventions
DRUGTranexamic acid
100 mg/kg load, then 10 mg/kg/hr
DRUGsaline
Placebo
Sponsors
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
The inclusion of the patients will depend on the following criteria: 1. All pediatric patients scheduled for primary or secondary repair of craniosynostosis with a frontal orbital advancement, or cranial vault reconstruction. 2. Patients will be between the ages of 6 months and 18 years old. 3. They will be \> than 5 kg. 4. All subjects being evaluated in the Craniofacial Clinic for primary or secondary repair of craniosynostosis will potentially be included in the study. Prior to inclusion in the study potential participants will be screened by history and laboratory data. The laboratory data will include a complete blood count, PT, PTT, type and cross, factor V leiden, anticardiolipin antibody, and lupus anticoagulant. The history will be obtained from the parents or current care takers. The medical records may be reviewed if there is a need for clarification.
Exclusion criteria
Patients that will be excluded from the study include the following: 1. Familial or personal coagulopathy risk-factor V leiden, anticardiolipin antibody, and lupus anticoagulant 2. Abnormal PT, PTT, Platelet count. or closing time. All patients presenting for craniofacial surgery have preoperative blood work performed which includes a type and screen, HCT, PLT, PT, PTT, and closing time. Patients who have abnormalities detected in their coagulation profile proceed on to a complete hematologic evaluation that includes an evaluation for Von Willebrand's Disease. 3. History of thrombotic episodes in the patient 4. Renal failure or hepatic failure. 5. Infants less than 5 kg 6. Age \< 6 months or \> 18 years old
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Volume (ml/kg) of Allogeneic Blood Exposure. | intraoperative and postoperative (24 hr) | This is the blood administered during surgery. The blood comes form the blood bank. It is not cell salvage blood. The volume was normalized by weight. |
| Number of Patients That Remained Transfusion Free | 24 hours | — |
Secondary
| Measure | Time frame |
|---|---|
| Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | (baseline, after osteotomies, and immediately after procedure) |
| Platelets | baseline, after osteotomies, immediately after surgery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tranexamic Acid Tranexamic acid (100 mg/kg load, 10 mg/kg/hr)
Tranexamic acid: 100 mg/kg load, then 10 mg/kg/hr
Patients are randomized to TXA or saline. This group is the TXA group. | 9 |
| Placebo Saline
saline: Placebo | 11 |
| Total | 20 |
Baseline characteristics
| Characteristic | Tranexamic Acid | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 11 Participants | 20 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 |
Outcome results
Primary
Number of Patients That Remained Transfusion Free
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid | Number of Patients That Remained Transfusion Free | 2 participants |
| Placebo | Number of Patients That Remained Transfusion Free | 0 participants |
Primary
Total Volume (ml/kg) of Allogeneic Blood Exposure.
This is the blood administered during surgery. The blood comes form the blood bank. It is not cell salvage blood. The volume was normalized by weight.
Time frame: intraoperative and postoperative (24 hr)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid | Total Volume (ml/kg) of Allogeneic Blood Exposure. | 16.1 ml/kg | Standard Deviation 13.9 |
| Placebo | Total Volume (ml/kg) of Allogeneic Blood Exposure. | 17.1 ml/kg | Standard Deviation 10.4 |
Secondary
Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure).
Time frame: (baseline, after osteotomies, and immediately after procedure)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tranexamic Acid | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PT -baseline | 15.1 seconds | Standard Deviation 0.84 |
| Tranexamic Acid | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PT-after osteotomies | 18.5 seconds | Standard Deviation 3.93 |
| Tranexamic Acid | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PT-immediately after surgery | 17.7 seconds | Standard Deviation 1.18 |
| Tranexamic Acid | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PTT -baseline | 34.6 seconds | Standard Deviation 2.92 |
| Tranexamic Acid | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PTT-after osteotomies | 37.2 seconds | Standard Deviation 9.75 |
| Tranexamic Acid | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PTT-immediately after surgery | 33.3 seconds | Standard Deviation 3.5 |
| Placebo | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PTT-after osteotomies | 34.6 seconds | Standard Deviation 3.62 |
| Placebo | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PT -baseline | 13.8 seconds | Standard Deviation 0.74 |
| Placebo | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PTT -baseline | 32.9 seconds | Standard Deviation 2.67 |
| Placebo | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PT-after osteotomies | 16.1 seconds | Standard Deviation 1.94 |
| Placebo | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PTT-immediately after surgery | 34.8 seconds | Standard Deviation 3.9 |
| Placebo | Effect of Tranexamic Acid on Prothrombin Time (PT), Partial Thromboplastin Time (PTT) at Three Time Points (Baseline, After Osteotomies, and Immediately After Procedure). | PT-immediately after surgery | 17 seconds | Standard Deviation 1.74 |
Secondary
Platelets
Time frame: baseline, after osteotomies, immediately after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tranexamic Acid | Platelets | platelets-baseline | 301 10^9 platelets/L | Standard Deviation 109 |
| Tranexamic Acid | Platelets | platelets-after osteotomies | 253 10^9 platelets/L | Standard Deviation 101 |
| Tranexamic Acid | Platelets | platelets-immediately after surgery | 223 10^9 platelets/L | Standard Deviation 89 |
| Placebo | Platelets | platelets-baseline | 364 10^9 platelets/L | Standard Deviation 125 |
| Placebo | Platelets | platelets-after osteotomies | 300 10^9 platelets/L | Standard Deviation 107 |
| Placebo | Platelets | platelets-immediately after surgery | 231 10^9 platelets/L | Standard Deviation 99 |