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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hyloris Developments

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Stomatognathic Diseases [C07]

Trial duration

6 May 2024 → ongoing

Decision date (initial)

2023-11-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Hyloris Developments SA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety, Efficacy, Others

To assess and compare the efficacy of Tranexamic Acid Oral Solution 5% with placebo to reduce clinically relevant postoperative oral bleeding (including clinically relevant orofacial hematomas) in subjects treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) and following a single or multiple tooth extraction(s) in all subjects.

Secondary objectives 5

1. To compare the efficacy of Tranexamic Acid Oral Solution 5% with placebo in the number of postoperative oral bleeding (including clinically and not clinically relevant bleedings and orofacial hematomas) in all subjects.
2. To assess and compare the efficacy of Tranexamic Acid Oral Solution 5% with placebo to reduce the number of delayed postoperative oral bleeding events in subjects treated with DOACs or VKAs and following a single or multiple tooth extraction in all subjects.
3. To assess and compare the efficacy of Tranexamic Acid Oral Solution 5% with placebo to reduce the number of early (less than 24 h post-tooth extraction) postoperative oral bleeding events in subjects treated with DOACs or VKAs and following a single or multiple tooth extraction in all subjects
4. To determine and compare the efficacy of Tranexamic Acid Oral Solution 5% with placebo on the perioperative and immediate postoperative oral bleeding (procedural bleeding) duration.
5. To assess the acceptability of Tranexamic Acid Oral Solution.

Conditions and MedDRA coding

Prevention of clinically relevant bleeding events in patients treated with direct anticoagulants or vitamin K antagonists and undergoing a single or multiple tooth extraction

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

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 anticoagulant (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. Scheduled to undergo a single or multiple tooth extraction
8. Considered as reasonably healthy to follow the study procedures as documented by the medical history, physical examination, and vital sign assessments
9. Subjects with a platelet count of 100,000-500,000 (inclusive) platelets per microliter
10. Subject with hemoglobin ≥ 12.0 g/dL (male) or ≥ 11.0 g/dL (female).
11. Willing to avoid alcohol consumption for the duration of the study
12. Willing and able to adhere to the study assessment schedule and other protocol requirements as evidenced by a written informed consent
13. Negative pregnancy test in females of childbearing potential at Screening and Day 1 visit.
14. 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 22

1. Any coagulation disorders requiring TXA.
2. 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.
3. Wisdom teeth extraction of Class II-III /Position B-C according to the Pell and Gregory classification (see Appendix 6).
4. History of severe allergy or allergic reactions or hypersensitivity to the study drug or any component of its formulations or related drugs or heparin
5. Subjects with type II, III and IV periodontitis (as per American Dental Association Classification) (see Appendix 1).
6. History of subarachnoid hemorrhage.
7. Active intravascular clotting (defined as a history of thrombosis within the past 3 months).
8. Blood in the urine (macroscopic hematuria) at Screening.
9. Renal function test result of estimated glomerular filtration rate ≤ 15 mL/min/1.73 m² at Screening.
10. 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.
11. Women with intended pregnancy or breast-feeding
12. Any ongoing or planned oncological treatment for the duration of subject`s participation in the study
13. Any immunocompromising condition.
14. Use of any recreational drugs or history of drug addiction.
15. Positive alcohol breath test at Screening and Day 1.
16. Participating in any other clinical study or has received treatment with any investigational drug or device within 3 months prior to screening.
17. 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]).
18. Severe uncontrolled arterial hypertension, e.g., > 200 mmHg systolic or > 110 mmHg diastolic blood pressure at two consecutive readings
19. Subjects who are found positive to human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) serological tests.
20. Women with intended pregnancy or breast-feeding
21. Planned soft (other than extraction site) or hard oral tissue biopsy on the day of the surgery
22. Subjects who are evaluated to have a negative risk-benefit ratio to participate in this study (e.g., high risk of severe bleeding).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of clinically relevant postoperative oral bleeding episodes (including clinically relevant orofacial hematomas) in all subjects

Secondary endpoints 5

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hyloris Developments

Sponsor organisation

Hyloris Developments

Address

Boulevard Gustave-Kleyer No 17

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Hyloris Developments

Contact name

Christophe Lyssens

Public contact point

Organisation

Hyloris Developments

Contact name

Christophe Lyssens

Third parties 3

Locations

4 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications