Effect of TXA Oral Sol 5% in Patients Treated With DOACs or VKA and Undergoing a Single or Multiple Tooth Extraction

A Randomized, Double-blind, Multi-center, Placebo-controlled, Parallel-group Phase 3 Study to Compare the Efficacy, Acceptability, and Safety of Tranexamic Acid Oral Solution 5% With Placebo in the Prevention of Clinically Relevant Bleeding Events in Subjects Treated With Direct Oral Anticoagulants or Vitamin K Antagonists and Undergoing a Single or Multiple Tooth Extraction.

The purpose of this study is to assess the effect of Tranexamic Acid Oral Solution 5% in patients treated with direct oral anticoagulants or vitamin K antagonists and undergoing a single or multiple tooth extraction.

Study Overview

• Status: Recruiting
• Conditions: Bleeding From Teeth; Bleeding Prophylaxis
• Intervention / Treatment: Drug: Tranexamic acid

Detailed Description

The purpose of this study is to compare the efficacy, acceptability, and safety of Tranexamic Acid Oral Solution 5% with placebo in the prevention of clinically relevant bleeding events in subjects treated with direct oral anticoagulants or vitamin K antagonists and undergoing a single or multiple tooth extraction.

A total of approximately 280 subjects will be randomized in two equal treatment groups (approximately 140 subjects per group) to receive Tranexamic Acid Oral Solution 5% or placebo solution for 7 days. Following screening, eligible subjects can be randomized within 14 days when all eligibility criteria are confirmed. Randomized subjects will undergo tooth extraction(s) and treatment period. The treatment period ends at Visit 5 followed by the follow-up period. The maximal study duration is about 4 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Christophe Lyssens; Phone Number: +3243460207; Email: clinical@hyloris.com

Study Locations

• Croatia
  • Rijeka, Croatia, 51000
    • Recruiting
    • Clinical Hospital Center Rijeka, Dental clinic
    • Contact: Vlatka Debeljak, Assoc. prof.
    • Principal Investigator: Vlatka Debeljak, Assoc. prof.
  • Split, Croatia, 21000
    • Not yet recruiting
    • University Hospital of Split Department of Oral surgery
    • Contact: Ivan Galić, Prof.
    • Principal Investigator: Ivan Galić, Prof.
  • Zagreb, Croatia, 10000
    • Not yet recruiting
    • University hospital Dubrava Department of oral surgery
    • Contact: Berislav Perić, Prof.
    • Principal Investigator: Berislav Perić, Prof.
  • Zagreb, Croatia, 10000
    • Recruiting
    • Dental Clinic Zagreb
    • Contact: Petra Fuchs, MD
    • Principal Investigator: Petra Fuchs, MD
• Hungary
  • Budapest, Hungary, 1085
    • Recruiting
    • Semmelweis Egyetem, Fogorvostudományi Kar, Arc-Állcsont-Szájsebészeti És Fogászati Klinika
    • Contact: Németh Zsolt, MD
    • Principal Investigator: Németh Zsolt, MD
  • Szeged, Hungary, 6722
    • Not yet recruiting
    • SZTE SZAKK Arc-, Állcsont- és Szájsebészeti Klinika
    • Contact: József Piffkó, Prof.Dr
    • Principal Investigator: József Piffkó, Prof.Dr
  • Veszprém, Hungary, 8200
    • Not yet recruiting
    • Arc-, Állcsont-, Szájsebészeti Osztály
    • Contact: Restár László, MD
    • Principal Investigator: Restár László, MD
• Romania
  • Bucuresti, Romania, 010825
    • Recruiting
    • "Dr. Carol Davila" Central Military Emergency University Hospital Bucharest
    • Contact: Ionescu Matei, MD
    • Principal Investigator: Ionescu Matei, MD
  • Bucuresti, Romania, 050533
    • Recruiting
    • Trident Clinic
    • Contact: Lucian Chirila, MD
    • Principal Investigator: Lucian Chirila, MD
  • Craiova, Romania, 200642
    • Recruiting
    • SCJU Craiova
    • Contact: Adi Camen, MD
    • Principal Investigator: Adi Camen, MD
• Spain
  • Barcelona, Spain, 08907
    • Not yet recruiting
    • Medicine and Healthcare Science Faculty of Barcelona University (Campus Bellvitge
    • Contact: Rui Figueiredo, MD
    • Principal Investigator: Rui Figueiredo, MD
  • Cadiz, Spain, 11009
    • Recruiting
    • Puerta del Mar University Hospital
    • Contact: Álvaro Povedano, MD
    • Principal Investigator: Álvaro Povedano, MD
  • Jerez de la Frontera, Spain, 11403
    • Not yet recruiting
    • Jerez Center Health Center
    • Contact: Javier Codeso, MD
    • Principal Investigator: Javier Codeso, MD
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: José Luis Carretero, MD
    • Principal Investigator: José Luis Carretero, MD
  • Sevilla, Spain, 41009
    • Recruiting
    • Institute of Biotechnology of Seville (IBIS)
    • Contact: Daniel Lagares, MD
    • Principal Investigator: Daniel Lagares, MD
• United States
  • California
    • Loma Linda, California, United States, 92350
      • Recruiting
      • Loma Linda University School of Dentistry
      • Contact: Montry Suprono, MD
      • Principal Investigator: Montry Suprono, MD
  • Connecticut
    • Stamford, Connecticut, United States, 06901
      • Not yet recruiting
      • Stamford Therapeutics Consortium
      • Contact: David Radin; Email: dradinmd@gmail.com
  • Utah
    • Millcreek, Utah, United States, 84107
      • Withdrawn
      • JBR Clinical Research (CenExel)
    • South Jordan, Utah, United States, 84107
      • Recruiting
      • Roseman University of Health Sciences, College of Dental Medicine
      • Contact: Man Hung, MD
      • Principal Investigator: Man Hung, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Provide their signed study informed consent to participate.
2. Male or female ≥ 18 years of age at screening.
3. Body mass index (BMI) between 18.5 kg/m2 and 35 kg/m2, inclusively and body weight ≥ 50 kg.
4. Treated regularly for ≥ 3 months with direct oral anticoagu19lant (e.g., edoxaban, apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (e.g., acenocoumarol, warfarin, etc.).
5. Subjects on VKAs can be enrolled if the subject's International Normalized Ratio (INR) at screening, but not more than 5 days before the dental extraction procedure is within the range of 2.0-3.5.
6. Subjects taking VKAs or DOACs can be enrolled if these are prescribed and used according to the approved product label.
7. Accepting to not discontinue his/her anticoagulant medication on the day of the extraction.
8. Scheduled to undergo a single or multiple (≤ 5 teeth, single-rooted, double-rooted, or multi-rooted, maximum 3 multi-rooted teeth and 2 different extraction sites) tooth extraction. Subjects with a single extraction site may have up to a maximum of 5 adjacent teeth extracted at the site, and subjects with two extraction sites may have up to a maximum of 3 adjacent extracted teeth at one site and 2 adjacent extracted teeth at the other site.
9. Considered as reasonably healthy to follow the study procedures as documented by the medical history, physical examination, and vital sign assessments.
10. Subjects with a platelet count of 100,000-500,000 (inclusive) platelets per microliter.
11. Subject with hemoglobin ≥ 12.0 g/dL (male) or ≥ 11.0 g/dL (female).
12. Willing to avoid alcohol consumption for the duration of the study.
13. Willing and able to adhere to the study assessment schedule and other protocol requirements as evidenced by a written informed consent.
14. Negative pregnancy test in females of childbearing potential at Screening and Day 1 visit.
15. Women must be post-menopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or willing to use highly effective method of birth control which is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (refer to Table 4 in protocol Section 8.2.11 for further information on acceptable and unacceptable birth control methods). The Investigator is responsible for determining whether the subject has adequate birth control for study participation.

Exclusion Criteria:

1. Any coagulation disorders requiring TXA.
2. Wisdom teeth extraction.
3. History of severe allergy or allergic reactions or hypersensitivity to the study drug or any component of its formulations or related drugs or heparin
4. Subjects with type IV periodontitis (as per American Dental Association Classification) (see Appendix 1).
5. History of subarachnoid hemorrhage.
6. Active intravascular clotting (defined as a history of thrombosis within the past 3 months).
7. Blood in the urine (macroscopic hematuria) at Screening.
8. Renal function test result of estimated glomerular filtration rate ≤ 15 mL/min/1.73 m² at Screening.
9. Any ongoing or planned dual anti-platelet treatment for the duration of subject's participation in the study (any 2 of the following: aspirin, dipyridamole, or any thienopyridine, i.e., clopidogrel, prasugrel, ticlopidine, ticagrelor). However, subjects receiving a very low dose aspirin (≤ 160 mg) may be enrolled.
10. Any ongoing or planned oncological treatment for the duration of subject's participation in the study.
11. Any immunocompromising condition.
12. Use of any recreational drugs or history of drug addiction.
13. Positive alcohol breath test at Screening and Day 1.
14. Participating in any other clinical study or has received treatment with any investigational drug or device within 3 months prior to screening.
15. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the investigational drug, might affect interpretation of the results of the study, or renders the subject at high risk for treatment complications (including but not limited to diseases such as uncontrolled diabetes, any haemato-oncological condition [e.g., leukemia], any congenital hematological condition [e.g., hemophilia]).
16. Severe uncontrolled arterial hypertension, e.g., > 200 mmHg systolic or > 110 mmHg diastolic blood pressure at two consecutive readings.
17. Subjects who are found positive to human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) serological tests.
18. Use of hormonal methods of birth control that increase the risk of thrombosis (e.g., estrogen-containing contraceptives). Refer to Table 4 in protocol Section 8.2.11 for further information on acceptable and unacceptable birth control methods.
19. Women with intended pregnancy or breast-feeding.
20. Planned soft (other than extraction site) or hard oral tissue biopsy on the day of the surgery.
21. Subjects who are evaluated to have a negative risk-benefit ratio to participate in this study (e.g., high risk of severe bleeding).

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: Treatment (T1); Standard hemostatic measures + Placebo matching with Tranexamic Acid Oral Solution 5%	Drug: Tranexamic acid; 7 days Oral rinsing following tooth extraction; Other Names: Tranexamic Acid Oral Solution 5%
Experimental: Treatment (T2); Standard hemostatic measures + Tranexamic Acid Oral Solution 5%	Drug: Tranexamic acid; 7 days Oral rinsing following tooth extraction; Other Names: Tranexamic Acid Oral Solution 5%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of clinically relevant postoperative oral bleeding episodes	Number of clinically relevant postoperative oral bleeding episodes (including clinically relevant orofacial hematomas)	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of delayed postoperative oral bleeding episodes	Number of delayed postoperative oral bleeding episodes, both clinically relevant and not clinically relevant, in all subjects.	7 days
Number of early postoperative oral bleeding episodes	Number of early (less than 24 h post-tooth extraction) postoperative oral bleeding episodes, both clinically relevant and not clinically relevant, in all subjects	7 days
Perioperative and immediate post-operative duration	Perioperative and immediate post-operative (procedural bleeding) duration (min, all types of oral bleeding).	7 days
Medication Acceptability Questionnaire (MAQ) completed	Medication Acceptability Questionnaire (MAQ) for Tranexamic Acid Oral Solution 5% use completed in all subjects	7 days
Number of postoperative oral bleeding episodes	Number of postoperative oral bleeding episodes (including clinically relevant and not clinically relevant bleedings and orofacial hematomas)	7 days

Collaborators and Investigators

• Sponsor: Hyloris Developments
• Investigators: Principal Investigator: Todd Bertoch, Dr., JBR Clinical Research (CenExcel)

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2023
• Primary Completion (Estimated): December 27, 2024
• Study Completion (Estimated): December 27, 2024

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 21, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Tranexamic Acid; bleeding teeth; Oral Solution; Tranexamic Acid Oral Solution 5%
• 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: HYL-P004-003; 2023-503719-13-00 (Other Identifier: EMEA)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No