Tooth Extraction
Conditions
Keywords
Anticoagulants, Tranexamic Acid
Brief summary
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.
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
Interventions
DRUGTranexamic Acid
Mouthwash
OTHERPlacebo
Mouthwash
Sponsors
Research Foundation Flanders
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants of Oral Bleeding | 7 days: from randomization till end of follow-up | Any oral bleeding (early or delayed; minor, clinically relevant or major) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Bleeding | 2 days | Any oral bleeding occurring after the extraction up to and including day 1 after the extraction |
| Delayed Bleeding | 6 days | Any oral bleeding occurring between day 2 and day 7 |
| Minor Bleeding | 7 days | Any oral bleeding not requiring unplanned medical contact |
| Clinically-relevant Bleeding | 7 days | Any oral bleeding requiring unplanned medical contact |
| Major Bleeding | 7 days | Any oral bleeding requiring blood transfusion, hospitalization or resulting in death |
| Procedural Bleeding Score | Day of extraction | The Procedural bleeding score assigned by operator (VAS 0-10): Visual analogue score: ranging from 0 (no bleeding) to 10 (unstoppable bleeding) |
| The Number of Participants With Unplanned Interruptions of Direct Oral Anticoagulant Therapy | 7 days | The number of particpants with unplanned interruptions of direct oral anticoagulant therapy |
| Number of Unplanned Medical Contacts | 7 days | Unplanned medical contact by phone, new consultation or hospitalization with any health care professional (dentist, general practioner, maxillofacial surgeon) |
| The Number of Reinterventions | 7 days | Any procedure in the oral cavity for the treatment of bleeding, performed by any dentist or maxillofacial surgeon |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcome Number of Participants With Thrombotic Event | 7 days | Number of participants with thrombotic events including myocardial infarction, stroke, systemic embolism and venous thrombo-embolism |
| Safety Outcome: Any Non-oral Bleeding | 7 days | Any non-oral bleeding |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
Tranexamic Acid: Mouthwash | 106 |
| Placebo 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).
Placebo: Mouthwash | 112 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Tranexamic Acid Group | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 74.8 years STANDARD_DEVIATION 8.8 | 72.7 years STANDARD_DEVIATION 10.7 | 73.7 years STANDARD_DEVIATION 9.8 |
| New oral anticoagulants (NOAC) apixaban | 29 Participants | 33 Participants | 62 Participants |
| New oral anticoagulants (NOAC) dabigatran | 18 Participants | 20 Participants | 38 Participants |
| New oral anticoagulants (NOAC) edoxaban | 21 Participants | 19 Participants | 40 Participants |
| New oral anticoagulants (NOAC) rivaroxaban | 38 Participants | 40 Participants | 78 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Belgium | 106 Participants | 112 Participants | 218 Participants |
| Sex: Female, Male Female | 25 Participants | 48 Participants | 73 Participants |
| Sex: Female, Male Male | 81 Participants | 64 Participants | 145 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 0 / 114 |
| other Total, other adverse events | 0 / 108 | 0 / 114 |
| serious Total, serious adverse events | 0 / 108 | 0 / 114 |
Outcome results
Primary
Number of Participants of Oral Bleeding
Any oral bleeding (early or delayed; minor, clinically relevant or major)
Time frame: 7 days: from randomization till end of follow-up
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or had a protocol deviation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tranexamic Acid Group | Number of Participants of Oral Bleeding | 28 Participants |
| Placebo Group | Number of Participants of Oral Bleeding | 32 Participants |
p-value: =0.7295% CI: [0.6, 1.42]Chi-squared
Secondary
Clinically-relevant Bleeding
Any oral bleeding requiring unplanned medical contact
Time frame: 7 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Group | Clinically-relevant Bleeding | 5 bleeding events |
| Placebo Group | Clinically-relevant Bleeding | 13 bleeding events |
p-value: =0.1595% CI: [0.13, 1.38]negative-binomial regression
Secondary
Delayed Bleeding
Any oral bleeding occurring between day 2 and day 7
Time frame: 6 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Group | Delayed Bleeding | 11 bleeding events |
| Placebo Group | Delayed Bleeding | 36 bleeding events |
p-value: =0.0395% CI: [0.12, 0.89]negative-binomial regression
Secondary
Early Bleeding
Any oral bleeding occurring after the extraction up to and including day 1 after the extraction
Time frame: 2 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Group | Early Bleeding | 35 bleeding events |
| Placebo Group | Early Bleeding | 49 bleeding events |
p-value: =0.3695% CI: [0.42, 1.37]negative-binomial regression
Secondary
Major Bleeding
Any oral bleeding requiring blood transfusion, hospitalization or resulting in death
Time frame: 7 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Group | Major Bleeding | 0 bleeding events |
| Placebo Group | Major Bleeding | 1 bleeding events |
Secondary
Minor Bleeding
Any oral bleeding not requiring unplanned medical contact
Time frame: 7 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Group | Minor Bleeding | 41 bleeding events |
| Placebo Group | Minor Bleeding | 72 bleeding events |
p-value: =0.1195% CI: [0.32, 1.12]negative-binomial regression
Secondary
Number of Unplanned Medical Contacts
Unplanned medical contact by phone, new consultation or hospitalization with any health care professional (dentist, general practioner, maxillofacial surgeon)
Time frame: 7 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Group | Number of Unplanned Medical Contacts | 10 number of unplanned medical contacts |
| Placebo Group | Number of Unplanned Medical Contacts | 27 number of unplanned medical contacts |
p-value: =0.0495% CI: [0.16, 0.98]negative-binomial regression
Secondary
Procedural Bleeding Score
The Procedural bleeding score assigned by operator (VAS 0-10): Visual analogue score: ranging from 0 (no bleeding) to 10 (unstoppable bleeding)
Time frame: Day of extraction
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid Group | Procedural Bleeding Score | 4 score on a scale | Standard Deviation 1.78 |
| Placebo Group | Procedural Bleeding Score | 4 score on a scale | Standard Deviation 1.82 |
Secondary
The Number of Participants With Unplanned Interruptions of Direct Oral Anticoagulant Therapy
The number of particpants with unplanned interruptions of direct oral anticoagulant therapy
Time frame: 7 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tranexamic Acid Group | The Number of Participants With Unplanned Interruptions of Direct Oral Anticoagulant Therapy | 6 Participants |
| Placebo Group | The Number of Participants With Unplanned Interruptions of Direct Oral Anticoagulant Therapy | 9 Participants |
p-value: =0.6695% CI: [0.26, 1.91]Chi-squared
Secondary
The Number of Reinterventions
Any procedure in the oral cavity for the treatment of bleeding, performed by any dentist or maxillofacial surgeon
Time frame: 7 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Group | The Number of Reinterventions | 7 number of reinterventions |
| Placebo Group | The Number of Reinterventions | 13 number of reinterventions |
p-value: =0.3795% CI: [0.17, 1.91]negative-binomial regression
Other Pre-specified
Safety Outcome: Any Non-oral Bleeding
Any non-oral bleeding
Time frame: 7 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid Group | Safety Outcome: Any Non-oral Bleeding | 12 bleeding events |
| Placebo Group | Safety Outcome: Any Non-oral Bleeding | 30 bleeding events |
p-value: <0.0195% CI: [0.18, 0.78]negative-binomial regression
Other Pre-specified
Safety Outcome Number of Participants With Thrombotic Event
Number of participants with thrombotic events including myocardial infarction, stroke, systemic embolism and venous thrombo-embolism
Time frame: 7 days
Population: Full analysis set: all randomized patients except for those who were lost to follow-up or who had a protocol violation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tranexamic Acid Group | Safety Outcome Number of Participants With Thrombotic Event | 0 Participants |
| Placebo Group | Safety Outcome Number of Participants With Thrombotic Event | 1 Participants |