Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001009505
Ethics application status
Approved
Date submitted
10/09/2015
Date registered
28/09/2015
Date last updated
18/02/2019
Date data sharing statement initially provided
18/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety of Dental Extraction on New Oral Anticoagulants (NOACs) withouT Stopping Therapy (DENTST study)
Scientific title
In patients having dental extractions, is continuing new oral anticoagulants (NOACs) as safe as continuing warfarin in terms of bleeding amount?
Secondary ID [1] 287358 0
Nil
Universal Trial Number (UTN)
U1111-1173-6906
Trial acronym
DENTST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dental extractions 296024 0
Anticoagulation 296048 0
Condition category
Condition code
Blood 296301 296301 0 0
Other blood disorders
Oral and Gastrointestinal 296319 296319 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study participants will continue their NOAC during dental extractions. There is currently no standard of care and no practice guidelines regarding NOAC management around dental extractions. It is up to the individual dentist to decide whether to stop the NOAC or not.
Intervention code [1] 292696 0
Treatment: Other
Comparator / control treatment
Warfarin continuation during dental extractions
Control group
Active

Outcomes
Primary outcome [1] 295955 0
To determine whether there is a difference in the blood loss following dental extractions between patients continuing NOACs and patients continuing warfarin. Bleeding amount will be defined by:
1. Weight difference of gauze required to achieve haemostasis.
2. Number of gauze required post procedure to achieve haemostasis.
3. Time to stable blood clot formation.
Timepoint [1] 295955 0
Amount of bleeding will be assessed immediately post-extraction (Patients will be monitored for at least 1 hour post-extraction, or until bleeding stops).
Secondary outcome [1] 317021 0
To determine whether there is a difference in the rate of significant bleeding post-dental extraction between patients continuing NOACs and patients continuing warfarin. Significant bleeding will be defined as the following:
(a) Major bleeding as defined by the International Society on Thrombosis and Haemostasis
a. Fatal bleeding, and/or
b. Bleeding that is symptomatic and occurs in a critical area or organ. For dental procedures, bleeding that threatens the airway, and/or
c. Bleeding causing a fall in haemoglobin level of 20 g/L or more, or leading to transfusion of two or more units of red cells, with temporal association within 24-48 h to the bleeding, and/or
d. Surgical site bleeding that requires a second surgical intervention and results in hospitalisation, and/or
e. Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability, as assessed by the surgeon, with an associated fall in haemoglobin level of at least 20 g/L, or transfusion of at least two units of red cells, indicated by the bleeding, with temporal association within 24 h to the bleeding.
(b) Clinically relevant non-major bleeding
a. Bleeding that requires medical intervention by health care provider, including oral anticoagulant (OAC) discontinuation, and/or
b. Bleeding that leads to hospitalisation or increased level of care, without requiring surgical intervention, and/or
c. Bleeding that leads to face to face evaluation.

Participants will be contacted by phone 48 hours after dental extraction and questioned about any bleeding. If the dentist has any concerns, a face-to-face review will be arranged. Participants will be asked to inform their study dentist of any bleeding after 48 hours and within 7 days of extraction.
Timepoint [1] 317021 0
Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [2] 317371 0
Correlation between pre-procedure NOAC drug levels and bleeding outcomes (i.e. amount of bleeding, rates of major and clinically relevant non-major bleeding).
Timepoint [2] 317371 0
NOAC drug levels will be measured on blood sample collected on the day of procedure, prior to the procedure. Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [3] 317372 0
To determine whether there is a safe lower limit and/or upper limit of the NOAC drug level for which dental extractions may be safely performed, by correlating pre-procedure NOAC drug levels with bleeding outcomes (i.e. amount of bleeding, rates of major and clinically relevant non-major bleeding).
Timepoint [3] 317372 0
NOAC drug levels will be measured on blood sample collected on the day of procedure, prior to the procedure. Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [4] 317373 0
Correlation between use of chlorhexidine mouth wash prior to dental extraction and bleeding outcomes.

Participants will be advised to use chlorhexidine mouth wash at initial appointment. Participants will be questioned about compliance with use of chlorhexidine mouth wash between initial appointment and day of extraction. This information will be correlated with bleeding outcomes (i.e. amount of bleeding, rates of major and clinically relevant non-major bleeding).
Timepoint [4] 317373 0
Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [5] 317374 0
Correlation between number of teeth extracted and bleeding outcomes.
Timepoint [5] 317374 0
Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [6] 317375 0
Correlation between procedure type (i.e. maxilla vs mandible, posterior vs anterior region, simple vs surgical extraction) and bleeding outcomes.
Timepoint [6] 317375 0
Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [7] 317376 0
Comparison between individual OACs (i.e. warfarin, dabigatran, rivaroxaban and apixavan) and bleeding outcomes.
Timepoint [7] 317376 0
Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [8] 317377 0
Correlation between age and bleeding outcomes.
Timepoint [8] 317377 0
Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [9] 317378 0
Correlation between pre-procedure creatinine clearance and bleeding outcomes.
Timepoint [9] 317378 0
Creatinine level will be measured on blood sample collected on the day of procedure, prior to the procedure. Cockroft Gault creatinine clearance will be calculated using the creatinine level, age and weight. Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [10] 317379 0
Correlation between concurrent antiplatelet therapy and bleeding outcomes.

A list of all the medications the patient takes will be ascertained. If a patient is taking any medication that affects platelet function (e.g. aspirin, clopidogrel, dipyridamole), their bleeding outcomes will be compared to that of patients who are not taking antiplatelet medications.
Timepoint [10] 317379 0
Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [11] 317380 0
Whether a patient smokes cigarettes or not will be ascertained. Smoking status will be correlated with bleeding outcomes.
Timepoint [11] 317380 0
Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [12] 317381 0
Correlation between pre-procedure C-reactive protein level, as an indicator of inflammation, and bleeding outcomes.
Timepoint [12] 317381 0
C-reactive protein level will be measured on blood sample collected on the day of procedure, prior to the procedure. Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.
Secondary outcome [13] 317573 0
Correlation between the number of contiguous teeth extracted and bleeding outcomes.
Timepoint [13] 317573 0
Amount of bleeding will be assessed immediately post-extraction. Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.

Eligibility
Key inclusion criteria
1. Requires simple or surgical dental extraction(s).
2. On therapeutic dose of dabigatran, rivaroxaban, apixaban or warfarin.
3. Able to give informed consent.
4. Age 18 or above.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant.
2. Concomitant use of dual anti-platelet therapy.
3. Inherited disorder of haemostasis.
4. Platelet count < 50 x 10^9/L.
5. Procedure for which operator requires OAC interruption.
6. OAC already ceased prior to procedure.
7. Patient on warfarin and INR < 2 or > 4.
8. Severe active oral infection associated with facial swelling.
9. Cockroft-Gaultcreatinine clearance < 25 ml/min for patients on dabigatran, < 30 ml/min for patients on rivaroxaban or apixaban.
11. Surgical extraction of wisdom teeth.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2015
Actual
10/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
400
Accrual to date
118
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4272 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 10222 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 291932 0
Self funded/Unfunded
Name [1] 291932 0
Country [1] 291932 0
Primary sponsor type
Individual
Name
Dr Jennifer Curnow
Address
Department of Haematology, Westmead Hospital, Cnr Hawkesbury Rd and Darcy Rd, Westmead, NSW, 2145
Country
Australia
Secondary sponsor category [1] 290601 0
None
Name [1] 290601 0
Address [1] 290601 0
Country [1] 290601 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293433 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 293433 0
Ethics committee country [1] 293433 0
Australia
Date submitted for ethics approval [1] 293433 0
15/09/2015
Approval date [1] 293433 0
28/01/2016
Ethics approval number [1] 293433 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59870 0
Dr Jennifer Curnow
Address 59870 0
Department of Haematology, Westmead Hospital, Cnr of Hawkesbury and Darcy Roads, Westmead, NSW, 2145
Country 59870 0
Australia
Phone 59870 0
+61 2 98456274
Fax 59870 0
Email 59870 0
[email protected]
Contact person for public queries
Name 59871 0
Jennifer Curnow
Address 59871 0
Department of Haematology, Westmead Hospital, Cnr of Hawkesbury and Darcy Roads, Westmead, NSW, 2145
Country 59871 0
Australia
Phone 59871 0
+61 2 98456274
Fax 59871 0
Email 59871 0
[email protected]
Contact person for scientific queries
Name 59872 0
Jennifer Curnow
Address 59872 0
Department of Haematology, Westmead Hospital, Cnr of Hawkesbury and Darcy Roads, Westmead, NSW, 2145
Country 59872 0
Australia
Phone 59872 0
+61 2 98456274
Fax 59872 0
Email 59872 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be made available publically.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseDental extractions on direct oral anticoagulants vs. warfarin: The DENTST study.2020https://dx.doi.org/10.1002/rth2.12307
N.B. These documents automatically identified may not have been verified by the study sponsor.