Randomized Clinical Trial With Aminocaproic Acid in the Prevention of Exodontic Bleeding in Anticoagulants Patients

Randomized Clinical Trial to Verify the Effectiveness of Topical Aminocaproic Acid in the Prevention of Post-exodontic Bleeding in Patients on Anticoagulants

Patients using anticoagulants present an increased risk of bleeding when subjected to oral surgery. Suspending or reducing the oral anticoagulant dose to perform invasive procedures, may result in thromboembolic events, putting patients health in risk. Recent studies advocate the dental surgery treatment without suspending the anticoagulant therapy, since the values of the international normalized ratio (INR) are in acceptable therapeutic levels and local measurements are taken for the hemostasis control. The aim of this study is to compare the effectiveness use of intra-alveolar epsilon amino caproic acid (EACA) associated to daily rinses with the drug, with routine post-surgical procedures, to control the post-exodontic bleeding in anticoagulated patients. Patients will be referred by the anticoagulation clinic of the Clementino Fraga Filho University Hospital. Once the study criteria is met patients will be randomly allocated into two groups and subsequently subjected to clinical and periodontal examination, radiographic examination and pre-operative periodontal therapy. Laboratory tests (partial thromboplastic time, prothrombin time, international normalized ratio and platelet count) will be held on the day of the extraction. Patients in group 1 ( EACA ) will receive a paste composed of 01 macerated EACA tablet (500 mg), mixed with 0.9% saline solution in the alveolar socket, and routine post-operative care. Additionally, patients will perform oral rinses three times a day, on the first two post-operative days, with a solution from the macerated EACA 500mg tablet diluted in 2 spoons of filtered water. Patients allocated in group 2 (control) will receive routine post-operative care. Classification of immediate bleeding will be held by the professional, on the day of the surgery, immediately after the suture and twenty minutes later and the delayed bleeding, recorded by the patient through a daily questionnaire. The Statistical Package for the Social Sciences (SPSS)© (IBM, Chicago, USA) 20.0 is used as the database and the Chi-square, Kruskal-Wallis and Mann-Whitney tests will be applied to statistical analysis of the results.The study was approved by the ethical and research committee of the Clementino Fraga Filho University Hospital . All patients will sign a free consent and informed term.

Study Overview

• Status: Unknown
• Conditions: Oral Hemorrhage
• Intervention / Treatment: Drug: Aminocaproic acid; Drug: lidocaine and epinephrine; Drug: Paracetamol; Other: Routine dental care

Detailed Description

All patients will be submitted to clinical and radiographic examination. Once selected, patients will receive hygiene instruction and will be submitted to full mouth scaling one week before the procedure with an ultrasonic device (CavitronR - Dentsply). The random allocation of patients will obey the order obtained in the computerized program Allocation 1.0 Software© (Isfahan, Iran, 2004). All patients should have the prothrombin time (PT) and INR, active thromboplastin partial time (aTPT) and platelet counts tests on the day of surgery. Patients who present INR< 2.0 e > 4 will be assessed by the medical team about the possibility of change in the dose of medication to the surgical procedure. Patients with predisposing heart conditions the bacterial endocarditis will receive antibiotic prophylaxis as recommendations from American Association of Cardiology (AHA) of 2007. All extraction procedures will be performed by non-traumatic conventional surgical techniques, under local anesthesia (2% lidocaine and epinephrine 1: 100,000). Just one extraction will be performed in each surgical procedure, by the same surgeon. All patients will receive digital compression of socket with sterile gauze for 5 minutes (Chompret 's manoeuver) and suture with non-resorbable wire, silk 3.0 type . Everyone will receive the base analgesic prescription Paracetamol 750 mg (Tylenol© - Johnson & Johnson), 01 tablet every 6 hours, by oral administration, for control of postoperative pain. Patients are divided into two groups:

Group 1 (EACA) - patients will receive the intra-alveolar application of a 500 mg tablet of the epsilon-amino caproic acid (EACA - Ipsilon® - Nikko Brazil, RJ) crushed in 0.9% saline. Additionally, they will be instructed to rinse with 500mg EACA tablets macerated and diluted in 2 tablespoons of water three times a day, in the two days after the extraction.

Group 2 (control) - patients will receive routine postoperative care.

Classification of Bleeding will be performed by the professional on the day of surgery at two times: one time (immediately after extraction) and time 2 (after 20 minutes). The bleeding will be classified as follows:

• No bleeding
• Light bleeding - blood in saliva
• Moderate Bleeding - bleeding controlled with local measures
• Severe Bleeding - when surgical intervention is required

Late bleeding will be recorded by the patient through daily questionnaire. The bleeding will be classified as follows:

• No bleeding
• Blood stained saliva
• Bleeding that stopped after compression bandage and ice pack for 20 minutes
• Bleeding stopped only after professional intervention

• Study Type: Interventional
• Enrollment (Anticipated): 154
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21864-440
      • Clementino Fraga Filho University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients over 18 years of age, use of warfarin sodium with or without anti-platelet aggregation, indicating simple extractions whose INR values are between 2.0 and 4.0 and that consent to participate in the study.

Exclusion Criteria:

• Patients with platelet count < 50,000 / mm3 Pregnant women or lactating Patients with hypersensitivity to the components of EACA. Patients with coagulopathies Patients who have impacted teeth, ankylosed or root morphological alterations that may complicate the procedure Patients who fail to submit laboratory and radiographic examinations necessary for the surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: aminocaproic acid; Crushed tablets inserted in the dental socket post-extraction	Drug: Aminocaproic acid; Crushed tablet in the dental socket; Other Names: Ipsilon©; Drug: lidocaine and epinephrine; 2%; Drug: Paracetamol; 750 mg
Other: Routine care after dental extraction; Chompret´s manoeuver, suture, surgical wound compression with gauze for 20 minutes	Drug: lidocaine and epinephrine; 2%; Drug: Paracetamol; 750 mg; Other: Routine dental care; Chompret´s manoeuver, suture, surgical wound compression with gauze for 20 minutes; Other Names: Routine procedures after dental extractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bleeding post-exodontic	No bleeding; Bleeding Light - blood in saliva; Moderate Bleeding - bleeding controlled with local measures; Severe Bleeding - when required surgical intervention and / or hospitalization	up to twenty minutes

Collaborators and Investigators

• Sponsor: Grupo de Estudos Multicentricos em Onco-Hematologia
• Collaborators: Rio de Janeiro State Research Supporting Foundation (FAPERJ)

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): July 1, 2015

Study Registration Dates

• First Submitted: September 10, 2014
• First Submitted That Met QC Criteria: September 11, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Estimate): September 12, 2014
• Last Update Submitted That Met QC Criteria: September 11, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: anticoagulation; extraction; epsilon amino caproic
• Additional Relevant MeSH Terms: Pathologic Processes; Stomatognathic Diseases; Mouth Diseases; Oral Manifestations; Hemorrhage; Oral Hemorrhage; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Non-Narcotic; Fibrin Modulating Agents; Antipyretics; Adrenergic alpha-Agonists; Adrenergic Agonists; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Lidocaine; Acetaminophen; Epinephrine; Aminocaproic Acid
• Other Study ID Numbers: AEAC2014