The Effect of Intravenous EACA on Blood Loss and Transfusion Requirements After Bilateral VRO

NCT ID: NCT02257580

Last Updated: 2022-11-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-01
• Study Completion Date: 2020-10-26

Brief Summary

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.

Detailed Description

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.

Conditions

E-Aminocaproic Acid; Bilateral Varus Rotational Osteotomy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

E-Aminocaproic acid

Intervention Type: 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}

Placebo

Equivalent volume of normal saline prepared by the pharmacy.

Group Type: PLACEBO_COMPARATOR

E-Aminocaproic acid

Intervention Type: 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}

Interventions

E-Aminocaproic acid

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}

Intervention Type: DRUG

Other Intervention Names

EACA

Eligibility Criteria

Inclusion Criteria

• Scheduled for bilateral varus rotational osteotomy (VRO) with or without associated soft tissue and osseous procedures

Exclusion Criteria

• Preoperative use of an anticoagulant (Plavix, warfarin, lovenox, etc.)
• History of hypersensitivity to EACA
• History of thromboembolic event (e.g., PE or DVT)
• History of renal insufficiency or failure
• Congenital or acquired coagulopathy as evidence by INR >1.4 or PTT > 1.4 times normal, or Platelets <150,000/mm3 on preoperative laboratory testing
• Use of hormone replacement therapy or hormonal contraceptive agents within days prior to surgery
• Use of acetylsalicylic acid (ASA), antiplatelet agents within 7 days prior to surgery
• Pregnant
• Breastfeeding
• Not received neuraxial anesthesia

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital for Special Surgery, New York

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Scher, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital for Special Surgery, New York

Locations

Hospital for Special Surgery

New York, New York, United States

Countries

United States

References

Eubanks JD. Antifibrinolytics in major orthopaedic surgery. J Am Acad Orthop Surg. 2010 Mar;18(3):132-8.

Reference Type: BACKGROUND

PMID: 20190103 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24557107 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24091932 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16138073 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18981961 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18978408 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11413428 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24034510 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2014-303

Identifier Type: -

Identifier Source: org_study_id