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E-Aminocaproic acid (EACA) is an anti-fibrinolytic agent that is used to decrease blood loss and transfusion requirements after several orthopedic procedures. The aim of this prospective double-blind placebo-controlled randomized trial is to determine whether IV EACA reduces intra-operative calculated total blood loss in patients undergoing bilateral varus rotational osteotomy (VRO). This study will also investigate intraoperative cell saver utilization, transfusion of allogeneic blood, hospital length-of-stay (LOS), short term complications, and long-term outcomes.This study will provide Level I evidence and has the potential to improve outcomes in children undergoing this procedure.
The participating anesthesiologists will not be blinded to study arms and hypotheses. Dr. Christopher Edmonds will be the head anesthesiologist for this study and will administer anesthetics to participants in this trial whenever his schedule makes it possible. Anesthesia will be conducted in a standardized fashion, with IV sedation using Versed and IV propofol, +/- Fentanyl and Ketamine . A Combined Spinal-Epidural (CSE) will be placed using 12.5-20 mg of bupivacaine. If a CSE is unsuccessful and an epidural and/or spinal are successfully obtained, the patient may still be included in the study. Patients not receiving neuraxial anesthesia will be excluded. If a patient requires general anesthesia, it will be induced at this time, but the patient will be excluded from the study. An arterial line and additional venous access will be obtained in standardized sterile practice. Sedation will be maintained with IV propofol. IV Valium, Toradol and IV acetaminophen will be given towards the end of the case, per anesthesiologist's discretion.
The blood pressure target will be 20-25% below baseline, which will be achieved primarily with the neuraxial anesthesia. For blood pressure above this range, the epidural will be dosed with a short-acting local anesthetic, and/or IV sedation will be titrated as per the anesthesiologist's judgment. For hypotension below this range, pressors or intravenous pressors will be given. An IV fluid bolus may also be given in the amount of 10-20cc/kg. Additional maintenance IV fluids will be given to maintain urine output of at least 0.5-1ml/kg/hr. The criteria for transfusion of blood products will be a hemoglobin level of < 7.0 g/dL or a hemoglobin level of < 10.0 g/dL with clinical signs of symptomatic anemia (e.g., unexplained tachycardia, hypotension unresponsive to fluids or vasopressors, change in mental status, low urine output, and shortness of breath). Blood will be administered 1 unit at a time, and the presence of symptoms or signs will be reassessed after each unit. This algorithm may be altered by the treating physician (e.g., PACU attending, surgeon, or the OR anesthesiologist), however all decisions will be supported by reasonable documentation. Drains will be removed on POD 2 unless specified by the attending surgeon. Of note, the chart of the patient will clearly indicate him/her as a study patient; a sticker will be place on the front of each participating patient's chart. Their enrollment will also be communicated in the clinician rounding notes for each patient. Drains will be labeled for each study participant as well, and nurses will record the drain outputs per their floor protocol.
Attending surgeons, orthopedic surgery residents, physician assistants and research assistants involved with this study will assist in data collection. For each patient, we will collect demographic data, pre-operative CBC data, intra-operative cell saver auto-transfusion volumes, post-operative number of packed red blood cell units transfused, post-operative CBC data, post-operative drain outputs, and post-operative complications. This information will be gathered from the peri-operative medical records and electronic medical records. Surgeons and clinical and research personnel will review medical chart and progress notes for evidence of clinically significant VTE, reoperation, hematoma, seroma, and infection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| E-Aminocaproic acid (EACA) | Experimental | An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case. |
|
| Placebo | Placebo Comparator | Equivalent volume of normal saline prepared by the pharmacy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| E-Aminocaproic acid | Drug | E-Aminocaproic acid (EACA) is a synthetic lysine analog that competitively inhibits the activation of plasminogen to plasmin and subsequently decreases the degree of fibrinolysis (Faraoni,2014} and is currently being used to decrease blood loss and transfusion requirements after orthopaedic procedures.(Eubanks,2010} Multiple meta analyses and retrospective and prospective studies have shown that EACA decreases blood loss and transfusion requirements after orthopaedic surgery{ McLeod,2013; Thompson, 2005; Thompson,2008; Gill,2008; Florentino-Pineda,2001}.Results from these studies also suggest that EACA will decreased post-operative morbidity, length of hospital stay, hospital costs, and complications.{Chimento,2013; Thompson,2005; Florentino-Pineda,2001} |
| Measure | Description | Time Frame |
|---|---|---|
| Intraoperative Calculated Total Blood Loss | Determined by estimated blood volume, calculated using difference in preoperative and postoperative hemoglobin and applied to the Nadler equation for estimating blood volume while adjusting for transfused hemoglobin to produce a single metric of calculated intraoperative blood loss. | Intraoperative (3-6 hours) |
| Measure | Description | Time Frame |
|---|---|---|
| Intraoperative Cell Saver Utilization | Number of participants requiring 1 unit of intraoperative cell saver transfusion. Patients either received or did not receive intraoperative cell saver transfusion. The maximum number of intraoperative units transfused in this study was 1 unit. The count of participants in the data table refers to the number of patients who received this transfusion. | Intraoperative, 1 day |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Scher, MD | Hospital for Special Surgery, New York | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital for Special Surgery | New York | New York | 10021 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20190103 | Background | Eubanks JD. Antifibrinolytics in major orthopaedic surgery. J Am Acad Orthop Surg. 2010 Mar;18(3):132-8. | |
| 24557107 | Background | Faraoni D, Goobie SM. The efficacy of antifibrinolytic drugs in children undergoing noncardiac surgery: a systematic review of the literature. Anesth Analg. 2014 Mar;118(3):628-36. doi: 10.1213/ANE.0000000000000080. |
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Patients aged 18 or younger with CP indicated for bilateral VRO. Hx of a thromboembolic event, renal insufficiency or failure, known hypersensitivity to EACA, congenital or acquired coagulopathy, pts that could not receive neuraxial anesthesia, being treated with anticoagulants, hormone replacement therapy or hormonal contraceptive agent were excluded. Pts undergoing bilateral VRO were identified and screened by the study surgeons. 2 screened pts declined to participate, 2 did not qualify.
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| ID | Title | Description |
|---|---|---|
| FG000 | E-Aminocaproic Acid (EACA) | An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case. |
| FG001 | Placebo | Equivalent volume of normal saline prepared by the pharmacy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | E-Aminocaproic Acid (EACA) | An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Intraoperative Calculated Total Blood Loss | Determined by estimated blood volume, calculated using difference in preoperative and postoperative hemoglobin and applied to the Nadler equation for estimating blood volume while adjusting for transfused hemoglobin to produce a single metric of calculated intraoperative blood loss. | Posted | Mean | Standard Deviation | mL | Intraoperative (3-6 hours) |
|
Day of surgery through 6 weeks post-op.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | E-Aminocaproic Acid (EACA) | An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Colson Zucker, Research Coordinator | Hospital for Special Surgery | 6467146029 | zuckerc@hss.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 10, 2014 | Aug 9, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 9, 2014 | Aug 9, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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|
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| Postoperative Allogeneic Blood Transfusion | The number of participants that required 1 unit of blood transfused post-operatively. Patients received blood if necessary post operatively, and the maximum number of units a patient received was 1. The count of participants refers to the number of patients who received this transfusion unit. | Post-Surgery, an expected average of 1 week |
| Post Operative Blood Loss | 24 hour drain output (mL) | Post-Surgery, 24 hours |
| Length of Hospital Stay | postoperative day of discharge after surgery- day of intake. | Post-Surgery, an expected average of 1 week |
| Complications [VTE (Symptomatic of DVT or PE), Infection (Superficial, Deep), Hematoma, Seroma, Reoperation, and Death] | Incidence of VTE (symptomatic of DVT or PE), infection (superficial, deep), hematoma, seroma, reoperation, and death, measured in person-years ( x cases per 100,000 person years) | an expected average of 1 week (post-surgery), Follow-up at 6 weeks |
| 24091932 | Background | McLeod LM, French B, Flynn JM, Dormans JP, Keren R. Antifibrinolytic Use and Blood Transfusions in Pediatric Scoliosis Surgeries Performed at US Children's Hospitals. J Spinal Disord Tech. 2015 Oct;28(8):E460-6. doi: 10.1097/BSD.0b013e3182a22a54. |
| 16138073 | Background | Thompson GH, Florentino-Pineda I, Poe-Kochert C. The role of amicar in decreasing perioperative blood loss in idiopathic scoliosis. Spine (Phila Pa 1976). 2005 Sep 1;30(17 Suppl):S94-9. doi: 10.1097/01.brs.0000175188.05542.a9. |
| 18981961 | Background | Thompson GH, Florentino-Pineda I, Poe-Kochert C, Armstrong DG, Son-Hing J. Role of Amicar in surgery for neuromuscular scoliosis. Spine (Phila Pa 1976). 2008 Nov 15;33(24):2623-9. doi: 10.1097/BRS.0b013e318187c046. |
| 18978408 | Background | Gill JB, Chin Y, Levin A, Feng D. The use of antifibrinolytic agents in spine surgery. A meta-analysis. J Bone Joint Surg Am. 2008 Nov;90(11):2399-407. doi: 10.2106/JBJS.G.01179. |
| 11413428 | Background | Florentino-Pineda I, Blakemore LC, Thompson GH, Poe-Kochert C, Adler P, Tripi P. The Effect of epsilon-aminocaproic acid on perioperative blood loss in patients with idiopathic scoliosis undergoing posterior spinal fusion: a preliminary prospective study. Spine (Phila Pa 1976). 2001 May 15;26(10):1147-51. doi: 10.1097/00007632-200105150-00011. |
| 24034510 | Background | Chimento GF, Huff T, Ochsner JL Jr, Meyer M, Brandner L, Babin S. An evaluation of the use of topical tranexamic acid in total knee arthroplasty. J Arthroplasty. 2013 Sep;28(8 Suppl):74-7. doi: 10.1016/j.arth.2013.06.037. |
| Placebo |
Equivalent volume of normal saline prepared by the pharmacy. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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Equivalent volume of normal saline prepared by the pharmacy.
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| Secondary | Intraoperative Cell Saver Utilization | Number of participants requiring 1 unit of intraoperative cell saver transfusion. Patients either received or did not receive intraoperative cell saver transfusion. The maximum number of intraoperative units transfused in this study was 1 unit. The count of participants in the data table refers to the number of patients who received this transfusion. | Posted | Count of Participants | Participants | Intraoperative, 1 day |
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| Secondary | Postoperative Allogeneic Blood Transfusion | The number of participants that required 1 unit of blood transfused post-operatively. Patients received blood if necessary post operatively, and the maximum number of units a patient received was 1. The count of participants refers to the number of patients who received this transfusion unit. | Posted | Count of Participants | Participants | Post-Surgery, an expected average of 1 week |
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| Secondary | Post Operative Blood Loss | 24 hour drain output (mL) | Posted | Mean | Standard Deviation | mL | Post-Surgery, 24 hours |
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| Secondary | Length of Hospital Stay | postoperative day of discharge after surgery- day of intake. | Posted | Mean | Full Range | days | Post-Surgery, an expected average of 1 week |
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| Secondary | Complications [VTE (Symptomatic of DVT or PE), Infection (Superficial, Deep), Hematoma, Seroma, Reoperation, and Death] | Incidence of VTE (symptomatic of DVT or PE), infection (superficial, deep), hematoma, seroma, reoperation, and death, measured in person-years ( x cases per 100,000 person years) | Posted | Number | cases per 100,000 person years | an expected average of 1 week (post-surgery), Follow-up at 6 weeks |
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| 0 |
| 16 |
| 0 |
| 16 |
| 0 |
| 16 |
| EG001 | Placebo | Equivalent volume of normal saline prepared by the pharmacy. | 0 | 12 | 0 | 12 | 0 | 12 |
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