Back to resultsTooth Extraction in Patients With Atrial Fibrillation in Use of New Oral Anticoagulants
Primary Purpose
Atrial Fibrillation, Periodontal Disease, Hemorrhage
Status
Completed
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Rivaroxaban
Dabigatran and Apixaban
Warfarin
Sponsored by
About this trial
This is an interventional supportive care trial for Atrial Fibrillation focused on measuring Dabigatran, Rivaroxaban, Apixaban, Warfarin, Tooth Extraction
Eligibility Criteria
Inclusion Criteria:
- Selection of patients: Both genders, aged over 18 years, regardless of ethnicity, marital status, nationality, naturalness or profession, with non-valvular atrial fibrillation using dabigatran or rivaroxaban or apixaban or warfarin, under medical outpatient treatment or during the hospitalization period.
- Dentistry: Patients with indications of exodontia of one to three permanent adjacent teeth erupted in the maxilla or mandible due to extensive dental caries or periodontal disease.
Exclusion Criteria:
- Clinical: Patients on concomitant use of antiplatelet agents or heparin, pregnant and lactating patients, with coagulation disorders, severe chronic renal insufficiency (CrCl <30), severe hepatopathies and proven to be allergic to lidocaine and / or epinephrine.
- Dentistry: Odontophobic, edentulous, or healthy teeth; Deciduous teeth and Included teeth.
- Regarding the time of medication intake: Regarding the time of medication intake Patients taking rivaroxaban who routinely take the medication between 5:00 a.m. to 4:00 p.m. (unworkable schedule for surgery) that do not accept a change in the intake schedule suggested by the attending physician.
Sites / Locations
- Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Rivaroxaban
Dabigatran and Apixaban
Warfarin
Arm Description
As the rivaroxaban is ingested 1x/day, the interval between a maximum peak concentration and the other peak is 24 hours. Therefore, the surgery will be performed between two peaks of maximum drug concentration, knowing that the maximum peak concentration is an average of two hours after ingestion. So the surgical procedure should be scheduled 14 hours (2 hours+ 12 hours) after the last medication intake.
As dabigatran and apixaban are taken 2x/day, the interval between two peak concentration is 12 hours.Taking into account the first two hours of maximum peak concentration and half the interval between two peaks (2 hours + 6 hours = 8 hours), the surgical procedure must be programmed eight hours after the last intake of medication.
The control group will consist of patients on chronic use of warfarin. The operation will be scheduled at any time, provided that the patient has INR value between 2.0 and 3.0 and test performed in maximum 15 days before surgery.
Outcomes
Primary Outcome Measures
A bleeding event (incidence of postoperative bleeding events)
To evaluate the safety of a protocol regarding the risks of bleeding after dental extractions performed in patients with non-valvular atrial fibrillation in continuous use of the new oral anticoagulants, we compared the incidence of postoperative bleeding events after dental extractions between patients in use of new oral anticoagulants and those treated of warfarin without withdrawal of oral anticoagulant therapy.
Secondary Outcome Measures
Full Information
NCT ID
NCT03181386
First Posted
June 2, 2017
Last Updated
June 11, 2022
Sponsor
University of Sao Paulo General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03181386
Brief Title
Tooth Extraction in Patients With Atrial Fibrillation in Use of New Oral Anticoagulants
Official Title
Prospective Study of the Assessment of the Dental Protocol for Tooth Extraction in Patients With Atrial Fibrillation in Continuous Use of New Oral Anticoagulants: A Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
May 3, 2017 (Actual)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
February 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety of a protocol which does not suspend the new oral anticoagulants (dabigatran, rivaroxaban and apixaban) in front of dental extractions in patients with non-valvular atrial fibrillation.
Detailed Description
The sample will be divided into three groups according to the pharmacokinetics of the oral anticoagulant: rivaroxaban 1x/day (group 1); dabigatran and apixabana 2x/day (group 2) and warfarin (control group). Extraction of one to three teeth will be scheduled, in the valley of the new oral anticoagulants' concentration, considered the period of smallest haemorrhagic risk without suspension. In group 1 the surgery will be scheduled 14 hours after the last intake, in group 2 the surgery will be scheduled 8 hours after the last intake, while the control group will undergo the procedure with INR values between 2.0 and 3,0. Hemostatic measures with tranexamic acid paste intra alveolar, suture and biological glue GRF® (gelatin, resorcinol and formaldehyde) and post operative care will be associated. The patients will be contacted after the procedure to inform the presence or absence of late bleeding. The patient should return 24 hours later to evaluate the surgical site. This protocol is based on Guidelines and scientific articles, pharmacokinetics and clinical experience of the authors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Periodontal Disease, Hemorrhage
Keywords
Dabigatran, Rivaroxaban, Apixaban, Warfarin, Tooth Extraction
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rivaroxaban
Arm Type
Experimental
Arm Description
As the rivaroxaban is ingested 1x/day, the interval between a maximum peak concentration and the other peak is 24 hours. Therefore, the surgery will be performed between two peaks of maximum drug concentration, knowing that the maximum peak concentration is an average of two hours after ingestion. So the surgical procedure should be scheduled 14 hours (2 hours+ 12 hours) after the last medication intake.
Arm Title
Dabigatran and Apixaban
Arm Type
Experimental
Arm Description
As dabigatran and apixaban are taken 2x/day, the interval between two peak concentration is 12 hours.Taking into account the first two hours of maximum peak concentration and half the interval between two peaks (2 hours + 6 hours = 8 hours), the surgical procedure must be programmed eight hours after the last intake of medication.
Arm Title
Warfarin
Arm Type
Active Comparator
Arm Description
The control group will consist of patients on chronic use of warfarin. The operation will be scheduled at any time, provided that the patient has INR value between 2.0 and 3.0 and test performed in maximum 15 days before surgery.
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Other Intervention Name(s)
Xarelto
Intervention Description
Rivaroxaban 15 or 20mg tablet by mouth, every 24 hours, continuous use.
Intervention Type
Drug
Intervention Name(s)
Dabigatran and Apixaban
Other Intervention Name(s)
Pradaxa and Eliquis
Intervention Description
Dabigatrana 110 or 150 mg tablet and Apixaban 2,5 or 5mg tablet by mouth, every 12 hours, continuous use.
Intervention Type
Drug
Intervention Name(s)
Warfarin
Other Intervention Name(s)
Marevan
Intervention Description
The dosage of Warfarin is individualized for each patient, according to the patient's TP/INR value. The value of TP/INR should be in the therapeutic dosage of 2.0 to 3.0
Primary Outcome Measure Information:
Title
A bleeding event (incidence of postoperative bleeding events)
Description
To evaluate the safety of a protocol regarding the risks of bleeding after dental extractions performed in patients with non-valvular atrial fibrillation in continuous use of the new oral anticoagulants, we compared the incidence of postoperative bleeding events after dental extractions between patients in use of new oral anticoagulants and those treated of warfarin without withdrawal of oral anticoagulant therapy.
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Selection of patients: Both genders, aged over 18 years, regardless of ethnicity, marital status, nationality, naturalness or profession, with non-valvular atrial fibrillation using dabigatran or rivaroxaban or apixaban or warfarin, under medical outpatient treatment or during the hospitalization period.
Dentistry: Patients with indications of exodontia of one to three permanent adjacent teeth erupted in the maxilla or mandible due to extensive dental caries or periodontal disease.
Exclusion Criteria:
Clinical: Patients on concomitant use of antiplatelet agents or heparin, pregnant and lactating patients, with coagulation disorders, severe chronic renal insufficiency (CrCl <30), severe hepatopathies and proven to be allergic to lidocaine and / or epinephrine.
Dentistry: Odontophobic, edentulous, or healthy teeth; Deciduous teeth and Included teeth.
Regarding the time of medication intake: Regarding the time of medication intake Patients taking rivaroxaban who routinely take the medication between 5:00 a.m. to 4:00 p.m. (unworkable schedule for surgery) that do not accept a change in the intake schedule suggested by the attending physician.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denise T Hachul, PhD
Organizational Affiliation
Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Itamara LI Neves, PhD
Organizational Affiliation
Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elaine M Higashi, S
Organizational Affiliation
Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ricardo S Neves, PhD
Organizational Affiliation
Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Francisco CC Darrieux, PhD
Organizational Affiliation
Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mauricio I Scanavacca, PhD
Organizational Affiliation
Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Official's Role
Study Chair
Facility Information:
Facility Name
Heart Institute of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
City
São Paulo
ZIP/Postal Code
05403000
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
After thesis defense, the IPD will be available on the Portal Digital Library of Theses and Dissertations of the University of São Paulo (http://www.teses.usp.br/index.php?option=com_jumi&fileid=12&Itemid=77&lang=ptbr), in a PDF file.
Citations:
PubMed Identifier
22922413
Citation
Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P; ESC Committee for Practice Guidelines (CPG). 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012 Nov;33(21):2719-47. doi: 10.1093/eurheartj/ehs253. Epub 2012 Aug 24. No abstract available. Erratum In: Eur Heart J. 2013 Mar;34(10):790. Eur Heart J. 2013 Sep;34(36):2850-1.
Results Reference
background
PubMed Identifier
23524440
Citation
Fakhri HR, Janket SJ, Jackson EA, Baird AE, Dinnocenzo R, Meurman JH. Tutorial in oral antithrombotic therapy: biology and dental implications. Med Oral Patol Oral Cir Bucal. 2013 May 1;18(3):e461-72. doi: 10.4317/medoral.19140.
Results Reference
background
PubMed Identifier
20876603
Citation
Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH; ESC Committee for Practice Guidelines. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace. 2010 Oct;12(10):1360-420. doi: 10.1093/europace/euq350. No abstract available. Erratum In: Europace. 2011 Jul;13(7):1058. Dosage error in article text.
Results Reference
background
PubMed Identifier
24561548
Citation
Halvorsen S, Atar D, Yang H, De Caterina R, Erol C, Garcia D, Granger CB, Hanna M, Held C, Husted S, Hylek EM, Jansky P, Lopes RD, Ruzyllo W, Thomas L, Wallentin L. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J. 2014 Jul 21;35(28):1864-72. doi: 10.1093/eurheartj/ehu046. Epub 2014 Feb 20.
Results Reference
background
PubMed Identifier
22668618
Citation
Little JW. New oral anticoagulants: will they replace warfarin? Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 May;113(5):575-80. doi: 10.1016/j.oooo.2011.10.006. Epub 2012 Mar 3.
Results Reference
background
PubMed Identifier
22668425
Citation
Firriolo FJ, Hupp WS. Beyond warfarin: the new generation of oral anticoagulants and their implications for the management of dental patients. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Apr;113(4):431-41. doi: 10.1016/j.oooo.2011.10.005.
Results Reference
background
PubMed Identifier
26386350
Citation
Elad S, Marshall J, Meyerowitz C, Connolly G. Novel anticoagulants: general overview and practical considerations for dental practitioners. Oral Dis. 2016 Jan;22(1):23-32. doi: 10.1111/odi.12371. Epub 2015 Nov 16.
Results Reference
background
PubMed Identifier
20352166
Citation
van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010 Jun;103(6):1116-27. doi: 10.1160/TH09-11-0758. Epub 2010 Mar 29.
Results Reference
background
PubMed Identifier
23850368
Citation
Romond KK, Miller CS, Henry RG. Dental management considerations for a patient taking dabigatran etexilate: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Sep;116(3):e191-5. doi: 10.1016/j.oooo.2013.05.001. Epub 2013 Jul 10.
Results Reference
background
PubMed Identifier
23920075
Citation
Davis C, Robertson C, Shivakumar S, Lee M. Implications of Dabigatran, a direct thrombin inhibitor, for oral surgery practice. J Can Dent Assoc. 2013;79:d74.
Results Reference
background
PubMed Identifier
23014816
Citation
Turpie AG, Kreutz R, Llau J, Norrving B, Haas S. Management consensus guidance for the use of rivaroxaban--an oral, direct factor Xa inhibitor. Thromb Haemost. 2012 Nov;108(5):876-86. doi: 10.1160/TH12-03-0209. Epub 2012 Sep 26.
Results Reference
background
PubMed Identifier
19196845
Citation
Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D. Metabolism and excretion of rivaroxaban, an oral, direct factor Xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos. 2009 May;37(5):1056-64. doi: 10.1124/dmd.108.025569. Epub 2009 Feb 5.
Results Reference
background
PubMed Identifier
21830957
Citation
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.
Results Reference
background
PubMed Identifier
24648742
Citation
Haas S, Bode C, Norrving B, Turpie AG. Practical guidance for using rivaroxaban in patients with atrial fibrillation: balancing benefit and risk. Vasc Health Risk Manag. 2014 Mar 10;10:101-14. doi: 10.2147/VHRM.S55246. eCollection 2014.
Results Reference
background
PubMed Identifier
21870978
Citation
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.
Results Reference
background
PubMed Identifier
22552763
Citation
Friedman RJ, Kurth A, Clemens A, Noack H, Eriksson BI, Caprini JA. Dabigatran etexilate and concomitant use of non-steroidal anti-inflammatory drugs or acetylsalicylic acid in patients undergoing total hip and total knee arthroplasty: no increased risk of bleeding. Thromb Haemost. 2012 Jul;108(1):183-90. doi: 10.1160/TH11-08-0589. Epub 2012 May 3.
Results Reference
background
PubMed Identifier
22782539
Citation
Hartter S, Sennewald R, Schepers C, Baumann S, Fritsch H, Friedman J. Pharmacokinetic and pharmacodynamic effects of comedication of clopidogrel and dabigatran etexilate in healthy male volunteers. Eur J Clin Pharmacol. 2013 Mar;69(3):327-39. doi: 10.1007/s00228-012-1304-8. Epub 2012 Jul 11.
Results Reference
background
PubMed Identifier
16920892
Citation
Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban--an oral, direct factor Xa inhibitor--are not affected by aspirin. J Clin Pharmacol. 2006 Sep;46(9):981-90. doi: 10.1177/0091270006292127.
Results Reference
background
PubMed Identifier
22225858
Citation
Eriksson BI, Rosencher N, Friedman RJ, Homering M, Dahl OE. Concomitant use of medication with antiplatelet effects in patients receiving either rivaroxaban or enoxaparin after total hip or knee arthroplasty. Thromb Res. 2012 Aug;130(2):147-51. doi: 10.1016/j.thromres.2011.12.005. Epub 2012 Jan 5.
Results Reference
background
PubMed Identifier
25668377
Citation
Scott A, Gibson J, Crighton A. The management of dental patients taking new generation oral anticoagulants. Prim Dent J. 2014 Nov;3(4):54-8. doi: 10.1308/205016814813877289.
Results Reference
background
PubMed Identifier
23625942
Citation
Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013 May;15(5):625-51. doi: 10.1093/europace/eut083.
Results Reference
background
PubMed Identifier
22986241
Citation
Hong C, Napenas JJ, Brennan M, Furney S, Lockhart P. Risk of postoperative bleeding after dental procedures in patients on warfarin: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Oct;114(4):464-8. doi: 10.1016/j.oooo.2012.04.017.
Results Reference
background
PubMed Identifier
22152517
Citation
Sie P, Samama CM, Godier A, Rosencher N, Steib A, Llau JV, Van der Linden P, Pernod G, Lecompte T, Gouin-Thibault I, Albaladejo P; Working Group on Perioperative Haemostasis; French Study Group on Thrombosis and Haemostasis. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis. 2011 Dec;104(12):669-76. doi: 10.1016/j.acvd.2011.09.001. Epub 2011 Oct 29.
Results Reference
background
PubMed Identifier
26592859
Citation
Clemm R, Neukam FW, Rusche B, Bauersachs A, Musazada S, Schmitt CM. Management of anticoagulated patients in implant therapy: a clinical comparative study. Clin Oral Implants Res. 2016 Oct;27(10):1274-1282. doi: 10.1111/clr.12732. Epub 2015 Nov 23.
Results Reference
background
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Tooth Extraction in Patients With Atrial Fibrillation in Use of New Oral Anticoagulants
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