Tranexamic Acid To Reduce Bleeding in Patients Treated With New Oral Anticoagulants Undergoing Dental Extraction (EXTRACT-NOAC)

In patients treated with direct oral anticoagulants, bleeding events during or after tooth extraction can lead to unscheduled interruption of the antithrombotic treatment and a potential increased risk of thrombo-embolic events. Therefore, an optimal strategy to minimize bleeding events after tooth extractions is required. In this study, the investigators want to assess whether adding tranexamic acid mouthwash reduces the number of bleeding events in patients treated with direct oral anticoagulants and undergoing a tooth extraction.

Study Overview

• Status: Terminated
• Conditions: Tooth Extraction
• Intervention / Treatment: Other: Placebo; Drug: Tranexamic Acid

Detailed Description

Interventional phase IV, randomized, double-blind, placebo-controlled trial:

• Feasibility: a 3-day regimen of tranexamic acid mouthwash in patients treated with direct oral anticoagulants
• Efficacy: reduction of bleeding events after tooth extraction compared to placebo
• Safety: any non-oral bleeding or thrombo-embolic events

• Study Type: Interventional
• Enrollment (Actual): 222
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients scheduled for dental extraction and treated with edoxaban, apixaban, rivaroxaban or dabigatran
• Not having taken the direct oral anticoagulant on the day of the extraction
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

• Subjects with any condition that as judged by the Investigator would place the subject at increased risk of harm if he/she participated in the study.
• Pregnancy or lactation
• Known allergic reaction to tranexamic acid

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; 10mL water as mouthwash with white cherry flavor in oral syringes. Once before tooth extraction and 3 times daily during 3 days post-extraction (starting day after extraction).	Other: Placebo; Mouthwash
Experimental: Tranexamic Acid Group; 10mL tranexamic acid mouthwash 10% in oral syringes. Once before tooth extraction and 3 times daily during 3 days post-extraction (starting day after extraction).	Drug: Tranexamic Acid; Mouthwash; Other Names: Exacyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral bleeding	Any oral bleeding (early or delayed; minor, clinically relevant or major)	7 days: from randomization till end of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural bleeding score	Bleeding score assigned by operator (VAS 0-10)	Day of extraction
Early bleeding	Any oral bleeding occurring after the extraction up to and including day 1 after the extraction	1 day
Delayed bleeding	Any oral bleeding occurring between day 2 and day 7	6 days
Minor bleeding	Any oral bleeding not requiring unplanned medical contact	7 days
Clinically-relevant bleeding	Any oral bleeding requiring unplanned medical contact	7 days
Major bleeding	Any oral bleeding requiring blood transfusion, hospitalization or resulting in death	7 days
The number of reinterventions	Any procedure in the oral cavity for the treatment of bleeding, performed by any dentist or maxillofacial surgeon	7 days
The number of unplanned interruptions of direct oral anticoagulant therapy	The number of unplanned interruptions of direct oral anticoagulant therapy	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcome: any non-oral bleeding	Any non-oral bleeding	7 days
Safety outcome: thrombotic event	All thrombotic events including myocardial infarction, stroke, systemic embolism and venous thrombo-embolism	7 days

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Research Foundation Flanders
• Investigators: Principal Investigator: Peter Verhamme, MD, PhD, UZ Leuven

Publications and helpful links

General Publications

• Ockerman A, Miclotte I, Vanhaverbeke M, Vanassche T, Belmans A, Vanhove J, Meyns J, Nadjmi N, Van Hemelen G, Winderickx P, Jacobs R, Politis C, Verhamme P. Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial. PLoS Med. 2021 May 3;18(5):e1003601. doi: 10.1371/journal.pmed.1003601. eCollection 2021 May.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Actual): March 19, 2020
• Study Completion (Actual): March 19, 2020

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 26, 2018
• First Posted (Actual): January 29, 2018

Study Record Updates

• Last Update Posted (Actual): August 17, 2020
• Last Update Submitted That Met QC Criteria: August 12, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Anticoagulants; Tranexamic Acid
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: S60131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No