ANZCTR - Registration

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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]

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

Anticoagulation

Condition category

Condition code

Blood

Other blood disorders

Oral and Gastrointestinal

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]

Treatment: Other

Comparator / control treatment

Warfarin continuation during dental extractions

Control group

Active

Outcomes

Primary outcome [1]

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]

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]

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]

Data on major bleeding and clinically relevant non-major bleeding up to 7 days post-extraction will be collected.

Secondary outcome [2]

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]

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]

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]

Secondary outcome [4]

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]

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]

Correlation between number of teeth extracted and bleeding outcomes.

Timepoint [5]

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]

Correlation between procedure type (i.e. maxilla vs mandible, posterior vs anterior region, simple vs surgical extraction) and bleeding outcomes.

Timepoint [6]

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]

Comparison between individual OACs (i.e. warfarin, dabigatran, rivaroxaban and apixavan) and bleeding outcomes.

Timepoint [7]

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]

Correlation between age and bleeding outcomes.

Timepoint [8]

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]

Correlation between pre-procedure creatinine clearance and bleeding outcomes.

Timepoint [9]

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]

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]

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]

Whether a patient smokes cigarettes or not will be ascertained. Smoking status will be correlated with bleeding outcomes.

Timepoint [11]

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]

Correlation between pre-procedure C-reactive protein level, as an indicator of inflammation, and bleeding outcomes.

Timepoint [12]

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]

Correlation between the number of contiguous teeth extracted and bleeding outcomes.

Timepoint [13]

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?

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]

Westmead Hospital - Westmead

Recruitment postcode(s) [1]

2145 - Westmead

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Western Sydney Local Health District Human Research Ethics Committee

Ethics committee address [1]

Westmead Research Office, Research and Education Network Building, Westmead Hospital, Darcy Rd, Westmead, NSW, 2145

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/09/2015

Approval date [1]

28/01/2016

Ethics approval number [1]

Summary

Brief summary

For patients on warfarin, the safety of having dental extractions while continuing to take the drug has been well established. Bleeding rates are not significantly different between patients who continue warfarin and those who temporarily discontinue warfarin for their dental extractions. Warfarin interruption for dental extractions has been associated with a 1% risk of blood clots, which can be fatal. International and local guidelines therefore recommend warfarin be continued for simple dental extractions.

There are currently no published studies to guide the management of new oral anticoagulants (NOACs, i.e. dabigatran, rivaroxaban and apixaban) around dental extractions. We hypothesise that the amount of bleeding post-extraction will be similar between patients who continue NOACs and patients who continue warfarin. By providing evidence that NOAC therapy can be safely continued for dental extractions, we believe that fewer patients will be exposed to the undue risk of developing blood clots by unnecessary interruption of anticoagulant therapy.

Trial website

Trial related presentations / publications

1. Brennan Y et al. Dental Extractions on NOACs without Stopping Therapy (DENTST) study: interim analysis". Oral presentation. HAA Annual Scientific Meeting. Sydney. October 2017. 
2. Gu Y et al. Dental Extractions on NOACs without Stopping Therapy (DENTST) study. Oral presentation. The Australasian Society of Special Care in Dentistry Walkabout Conference. Brisbane. September 2017. 
3. Brennan Y et al. Dental Extractions on NOACs without Stopping Therapy (DENTST) study: interim analysis. Poster presentation. ISTH Congress. Berlin. July 2017.

Public notes

Contacts

Principal investigator

Name

Dr Jennifer Curnow

Address

Department of Haematology, Westmead Hospital, Cnr of Hawkesbury and Darcy Roads, Westmead, NSW, 2145

Country

Australia

Phone

+61 2 98456274

Fax

jennifer.curnow@sydney.edu.au

Contact person for public queries

Name

Jennifer Curnow

Address

Department of Haematology, Westmead Hospital, Cnr of Hawkesbury and Darcy Roads, Westmead, NSW, 2145

Country

Australia

Phone

+61 2 98456274

Fax

jennifer.curnow@sydney.edu.au

Contact person for scientific queries

Name

Jennifer Curnow

Address

Department of Haematology, Westmead Hospital, Cnr of Hawkesbury and Darcy Roads, Westmead, NSW, 2145

Country

Australia

Phone

+61 2 98456274

Fax

jennifer.curnow@sydney.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

Source	Title	Year of Publication	DOI
Embase	Dental extractions on direct oral anticoagulants vs. warfarin: The DENTST study.	2020	https://dx.doi.org/10.1002/rth2.12307

N.B. These documents automatically identified may not have been verified by the study sponsor.

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