Clinical Trial Results:
Tranexamic Acid to reduce bleeding in patients treated with new oral anticoagulants undergoing dental extraction (EXTRACT-NOAC)
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Summary
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EudraCT number |
2017-001426-17 |
Trial protocol |
BE |
Global end of trial date |
19 Mar 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Jun 2021
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First version publication date |
13 Jun 2021
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Other versions |
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Summary report(s) |
EXTRACT-NOAC |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
1M
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03413891 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University Hospitals Leuven
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Sponsor organisation address |
Herestraat 49, Leuven, Belgium, 3000
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Public contact |
Barbara Debaveye, Universitary Hospitals Leuven (Gasthuisberg), 032 16341463, barbara.debaveye@uzleuven.be
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Scientific contact |
Barbara Debaveye, Universitary Hospitals Leuven (Gasthuisberg), 032 16341463, barbara.debaveye@uzleuven.be
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Mar 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Mar 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate whether TXA mouthwash reduces post-extraction bleeding in patients who undergo dental extraction and are treated with NOACs
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Protection of trial subjects |
Potential risks of systemic administration of TXA, as reported by the package insert, include convulsions, blurred vision, haematuria and thrombo-embolism. However, none of these potential risks have been shown to be present in case of mouthwash as compared to systemic administration. This can be explained by the low systemic TXA levels in case of administration by mouthwash.
Therefore, the immediate potential risk of TXA mouthwash is limited to:
• Allergic reaction
• Bleeding in case of extensive or traumatic mechanical rinsing
There are no known long-term risks. Because of these limited potential risks, the potential benefit of this treatment is expected to outweigh the risks.
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Background therapy |
0 | ||
Evidence for comparator |
0 | ||
Actual start date of recruitment |
07 Feb 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 222
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Worldwide total number of subjects |
222
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EEA total number of subjects |
222
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
33
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From 65 to 84 years |
163
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85 years and over |
26
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Recruitment
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Recruitment details |
First patient first visit: 7 feb 2018 Last patient last visit: 19 nov 2020 Total randomized patients: 222 | ||||||||||||||||||
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Pre-assignment
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Screening details |
293 patients were assessed for eligibility, of whom 71 patients were not eligible: - 35 declined to participate - 29 did not meet inclusion criteria - 4 language barriers - 3 tooth extractions annulated | ||||||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
222 | ||||||||||||||||||
Number of subjects completed |
222 | ||||||||||||||||||
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Period 1
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Period 1 title |
Patients Full Analysis Set (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
Blinding implementation details |
A computer-generated block-randomization list will be generated by an independent person for treatment allocation. Labeling of the study drug and matched placebo will occur by an independent person.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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tranexamic acid | ||||||||||||||||||
Arm description |
10% (1g/10mL) tranexamic acid mouthwash, 10 doses: 1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
tranexamic acid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Mouthwash
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Routes of administration |
Topical use
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Dosage and administration details |
10 doses: 1 dose immediatly prior to dental extraction, 3 doses per day for 3 days thereafter.
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
cherry-flavoured water as mouthwash, 10 doses: 1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
cherry-flavoured water
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Mouthwash
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Routes of administration |
Topical use
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Dosage and administration details |
1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter.
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Baseline characteristics reporting groups
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Reporting group title |
tranexamic acid
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Reporting group description |
10% (1g/10mL) tranexamic acid mouthwash, 10 doses: 1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
cherry-flavoured water as mouthwash, 10 doses: 1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
tranexamic acid
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Reporting group description |
10% (1g/10mL) tranexamic acid mouthwash, 10 doses: 1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter. | ||
Reporting group title |
Placebo
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Reporting group description |
cherry-flavoured water as mouthwash, 10 doses: 1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter. | ||
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End point title |
Patients with oral bleeds until 7 days after dental extraction | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From the day of the dental extraction until 7 days thereafter.
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| Notes [1] - 32 |
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Statistical analysis title |
Analysis primary endpoint | |||||||||
Comparison groups |
tranexamic acid v Placebo
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Number of subjects included in analysis |
218
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.72 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Risk ratio (RR) | |||||||||
Point estimate |
0.57
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.31 | |||||||||
upper limit |
1.05 | |||||||||
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End point title |
Type and number of oral bleeds until 7 days after dental extraction | ||||||||||||||||||||||||
End point description |
Bleedings are defined as:
- Minor bleeding: any oral bleeding experienced by the patient that does not require medical contact. Eg. blood on the pillow, bleeding requiring the use of additional gauzes, clear red bleeding when spitting out the mouthwash
- Clinically relevant bleeding: any oral non-major bleeding requiring unplanned medical contact (by phone or with any health care professional (dentist, general practitioner, maxillofacial surgeon), with or without re-intervention
- Early bleeding: any oral bleeding occurring after the extraction up to and including day 1 after the extraction
- Delayed bleeding: any oral bleeding occurring between day 2 and day 7
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End point type |
Secondary
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End point timeframe |
From the day of the dental extraction until 7 days thereafter.
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Statistical analysis title |
Analysis secondary oral bleeding endpoints | ||||||||||||||||||||||||
Statistical analysis description |
The secondary outcomes were were analyzed by means of a logistic regression (for the number of patients with oral bleeds) and negative-binomial regression model (for the number of oral bleeds). The treatment effect was estimated as a rate ratio (the number of bleeds per patient during the first seven days after dental extraction).
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Comparison groups |
tranexamic acid v Placebo
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Number of subjects included in analysis |
218
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.07 [2] | ||||||||||||||||||||||||
Method |
negative-binomial regression model | ||||||||||||||||||||||||
Parameter type |
rate ratio | ||||||||||||||||||||||||
Point estimate |
0.57
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.31 | ||||||||||||||||||||||||
upper limit |
1.05 | ||||||||||||||||||||||||
| Notes [2] - P-value is given for all oral bleeding events. |
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End point title |
Number of reinterventions for oral bleeding | |||||||||
End point description |
A reintervention is defined as any procedure in the oral cavity for the treatment of bleeding, performed by any dentist or maxillofacial surgeon, except for rinsing the extraction socket with saline.
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End point type |
Secondary
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End point timeframe |
from day of dental extraction until 7 days thereafter
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Statistical analysis title |
Sec. Outcome number of reinterventions | |||||||||
Comparison groups |
tranexamic acid v Placebo
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Number of subjects included in analysis |
218
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.37 | |||||||||
Method |
negative-binomial regression model | |||||||||
Parameter type |
Rate Ratio | |||||||||
Point estimate |
0.57
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.17 | |||||||||
upper limit |
1.91 | |||||||||
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End point title |
Number of unplanned medical contacts | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From the day of dental extraction until 7 days thereafter
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Statistical analysis title |
Sec. Outcome number of unplanned medical contacts | |||||||||
Comparison groups |
tranexamic acid v Placebo
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Number of subjects included in analysis |
218
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.04 | |||||||||
Method |
negative-binomial regression model | |||||||||
Parameter type |
Rate Ratio | |||||||||
Point estimate |
0.39
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.16 | |||||||||
upper limit |
0.98 | |||||||||
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End point title |
Number of NOAC interruptions | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From re-intake of the NOAC after dental extraction until 7 days after dental extraction
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Statistical analysis title |
Sec. Outcome number of NOAC interruptions | |||||||||
Comparison groups |
tranexamic acid v Placebo
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Number of subjects included in analysis |
218
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.66 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Risk ratio (RR) | |||||||||
Point estimate |
0.7
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.26 | |||||||||
upper limit |
1.91 | |||||||||
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End point title |
Number of non-oral bleeds | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From day of the dental extraction until 7 days thereafter
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Statistical analysis title |
Sec. Outcome number of non-oral bleeds | |||||||||
Comparison groups |
tranexamic acid v Placebo
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Number of subjects included in analysis |
218
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.01 | |||||||||
Method |
negative-binomial regression model | |||||||||
Parameter type |
Rate Ratio | |||||||||
Point estimate |
0.37
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.18 | |||||||||
upper limit |
0.78 | |||||||||
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End point title |
Safety endpoint from inclusion until last visit | |||||||||
End point description |
thrombotic events
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End point type |
Other pre-specified
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End point timeframe |
From inclusion until last visit
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| No statistical analyses for this end point | ||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
From inclusion until 7 days after dental extraction.
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Assessment type |
Systematic | |||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
short description | |||||||||||||||
Dictionary version |
0
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Reporting groups
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Reporting group title |
Tranexamic acid
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Reporting group description |
10% (1g/10mL) tranexamic acid mouthwash, 10 doses: 1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter. | |||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
cherry-flavoured water as mouthwash, 10 doses: 1 dose immediately prior to dental extraction, 3 doses per day for 3 days thereafter. | |||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Adverse events (non-oral bleeds and thrombotic events) were recorded as endpoints. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
