Efficacy and Safety of Tranexamic Acid Oral Solution 5% in Preventing Postoperative Bleeding in Patients on Anticoagulants Undergoing Dental Extractions
- Trial ID
- 2023-503719-13-00
- Protocol
- HYL-P004-003
- Sponsor
- Hyloris Developments
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess and compare the **efficacy** of Tranexamic Acid Oral Solution 5% with placebo in reducing clinically relevant postoperative oral bleeding, including clinically relevant orofacial hematomas, in subjects treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) following a single or multiple tooth extraction. This is clinically relevant as it addresses the management of bleeding risks in patients undergoing dental procedures while on anticoagulant therapy, which is a common clinical challenge.
Secondary objectives include:
- Comparing the efficacy of Tranexamic Acid Oral Solution 5% with placebo in the number of not clinically relevant postoperative oral bleeding events, including orofacial hematomas.
- Assessing and comparing the efficacy to reduce the number of delayed postoperative oral bleeding events in subjects treated with DOACs or VKAs following tooth extraction.
- Evaluating the efficacy to reduce the number of early postoperative oral bleeding events (less than 24 hours post-extraction) in subjects treated with DOACs or VKAs.
- Determining and comparing the efficacy on the duration of perioperative and immediate postoperative oral bleeding.
- Assessing the acceptability of Tranexamic Acid Oral Solution.
Participants
The clinical trial involves a total of **56 participants** who are undergoing a study to assess the efficacy of Tranexamic Acid Oral Solution 5% in reducing postoperative oral bleeding in patients treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) following tooth extraction. The study population includes both **male and female** subjects aged **18 years and older**. Participants are required to have a **body mass index (BMI)** between 18.5 kg/m² and 35 kg/m² and a body weight of at least 50 kg. All subjects must be regularly treated with DOACs or VKAs for at least three months prior to the study. The trial includes individuals who are considered reasonably healthy based on medical history, physical examination, and vital sign assessments. Participants must have a hemoglobin level of at least 12.0 g/dL for males and 11.0 g/dL for females, and a platelet count between 100,000 and 500,000 platelets per microliter. Lifestyle considerations include a willingness to avoid alcohol consumption during the study period. The selection process ensures that participants are capable of adhering to the study assessment schedule and other protocol requirements. The trial population is not limited by gender, and both male and female subjects are included. The study also considers vulnerable populations, ensuring comprehensive representation within the trial.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled, parallel-group phase 3 study. The primary objective is to assess the efficacy of **Tranexamic Acid Oral Solution 5%** compared to placebo in reducing clinically relevant postoperative oral bleeding in patients treated with direct oral anticoagulants or vitamin K antagonists undergoing tooth extraction. The trial is expected to commence on November 7, 2023, and conclude by June 27, 2024, with a maximum treatment period of 7 days for each participant.
Participants will be required to attend several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, hemoglobin levels, and treatment history with anticoagulants. Following successful screening, participants will be randomized to receive either the active treatment or placebo. Subsequent visits will include follow-up assessments to monitor for any postoperative bleeding episodes and to evaluate the acceptability of the medication. The end-of-study visit will involve a final assessment of the participant's health status and the collection of any remaining data.
The expected duration of participant involvement is approximately 7 days, with conditions for early termination including non-compliance with study protocols, adverse events, or withdrawal of consent. The primary endpoint is the number of clinically relevant postoperative oral bleeding episodes, while secondary endpoints include the number of non-clinically relevant bleeding episodes, delayed bleeding episodes, and the duration of perioperative bleeding. The study will also assess the acceptability of the Tranexamic Acid Oral Solution 5% through a Medication Acceptability Questionnaire.
Treatment
The clinical trial involves the administration of **Tranexamic Acid Oral Solution 5%**, which is an experimental medication formulated as an oral solution. The active substance in this medication is **tranexamic acid**, a chemical compound classified under the ATC code B02AA02. The solution is intended for **oromucosal use** and is provided by Hyloris Developments SA. The maximum treatment period for this medication is seven days, although specific dosing details such as the maximum daily dose amount and total dose amount are not specified in the available data. The trial aims to evaluate the efficacy of this solution in reducing clinically relevant postoperative oral bleeding in subjects undergoing tooth extraction while on direct oral anticoagulants or vitamin K antagonists.
The study also includes a **placebo** that matches the Tranexamic Acid Oral Solution 5%. This placebo is designed to mimic the experimental medication in appearance and administration route, ensuring the study remains double-blind. The placebo is also provided in an oral solution form for oromucosal use, aligning with the administration method of the active treatment. The placebo is utilized to establish a control group, allowing for a comparative analysis of the efficacy and safety of the Tranexamic Acid Oral Solution 5% in preventing bleeding events.
Efficacy
The efficacy of Tranexamic Acid Oral Solution 5% will be assessed in a randomized, double-blind, multi-center, placebo-controlled, parallel-group phase 3 clinical trial. The primary endpoint for evaluating efficacy is the number of clinically relevant postoperative oral bleeding episodes, including clinically relevant orofacial hematomas, in all subjects. Secondary endpoints include the number of non-clinically relevant postoperative oral bleeding episodes, the number of delayed postoperative oral bleeding episodes, and the number of early postoperative oral bleeding episodes, both clinically relevant and non-clinically relevant. Additionally, the duration of perioperative and immediate postoperative bleeding will be measured, along with the completion of the Medication Acceptability Questionnaire (MAQ) for Tranexamic Acid Oral Solution 5% by all subjects.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Provide their signed study informed consent to participate.
- Male or female ≥ 18 years of age at screening.
- Body mass index (BMI) between 18.5 kg/m2 and 35 kg/m2, inclusively and body weight ≥ 50 kg.
- Treated regularly for ≥ 3 months with direct oral anticoagulant (e.g., edoxaban, apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (e.g., acenocoumarol, warfarin, etc.).
- 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.
- Subjects taking VKAs or DOACs can be enrolled if these are prescribed and used according to the approved product label
- Scheduled to undergo a single or multiple tooth extraction
- Considered as reasonably healthy to follow the study procedures as documented by the medical history, physical examination, and vital sign assessments
- Subjects with a platelet count of 100,000-500,000 (inclusive) platelets per microliter
- Subject with hemoglobin ≥ 12.0 g/dL (male) or ≥ 11.0 g/dL (female).
- Willing to avoid alcohol consumption for the duration of the study
- Willing and able to adhere to the study assessment schedule and other protocol requirements as evidenced by a written informed consent
- Negative pregnancy test in females of childbearing potential at Screening and Day 1 visit.
- 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 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
- Any coagulation disorders requiring TXA.
- 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.
- Wisdom teeth extraction of Class II-III /Position B-C according to the Pell and Gregory classification (see Appendix 6).
- History of severe allergy or allergic reactions or hypersensitivity to the study drug or any component of its formulations or related drugs or heparin
- Subjects with type II, III and IV periodontitis (as per American Dental Association Classification) (see Appendix 1).
- History of subarachnoid hemorrhage.
- Active intravascular clotting (defined as a history of thrombosis within the past 3 months).
- Blood in the urine (macroscopic hematuria) at Screening.
- Renal function test result of estimated glomerular filtration rate ≤ 15 mL/min/1.73 m² at Screening.
- 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.
- Women with intended pregnancy or breast-feeding
- Any ongoing or planned oncological treatment for the duration of subject`s participation in the study
- Any immunocompromising condition.
- Use of any recreational drugs or history of drug addiction.
- Positive alcohol breath test at Screening and Day 1.
- Participating in any other clinical study or has received treatment with any investigational drug or device within 3 months prior to screening.
- 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]).
- Severe uncontrolled arterial hypertension, e.g., > 200 mmHg systolic or > 110 mmHg diastolic blood pressure at two consecutive readings
- Subjects who are found positive to human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) serological tests.
- Women with intended pregnancy or breast-feeding
- Planned soft (other than extraction site) or hard oral tissue biopsy on the day of the surgery
- Subjects who are evaluated to have a negative risk-benefit ratio to participate in this study (e.g., high risk of severe bleeding).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Croatia | Recruiting | 07 Nov 2023 | 72 |
 Hungary | Not Recruiting | 07 Nov 2023 | 60 |
 Romania | Recruiting | 07 Nov 2023 | 60 |
 Spain | Recruiting | 07 Nov 2023 | 90 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo matching with Tranexamic Acid Oral Solution 5% of Hyloris Developments SA, Belgium | Placebo | N/A | — | — | — | N/A |
Tranexamic Acid Oral Solution 5% | Test | ORAL SOLUTION | OROMUCOSAL USE | 000 | 7 | PRD10203251 |