Dental Implants in Patients Under Oral Anticoagulant Therapy

NCT04846114 | Completed

• 1 other identifier: VRID 1500
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluated the outcomes in the post-operative recovery following dental implant surgery in patients who continued on oral anticoagulated therapy (OAT) with warfarin. The primary outcome of this study was to evaluate bleeding within the first 5 days post-surgery and presence of intraoral/extraoral hematomas in skin and mucosa oral.

Conditions

Oral Anticoagulant Therapy

Keywords

Dental Implants; Anticoagulant Therapy; Warfarin; Tranexamic Acid; Bismuth subgallate

Outcome Measures

Primary Outcomes (4)

• Number of immediate postoperative bleeding events

  0: no bleeding; -1: mild bleeding defined as minor oozing from the wound incision controlled with compressive gauze only -2: moderate bleeding associated with the presence of large clots continuously disrupting the surgical area and requiring additional hemostatic measures; -3: severe bleeding requiring further medical control of coagulation

  Within the first 30 minutes after surgery

• Number of short-term bleeding events

  0: no bleeding; -1: mild bleeding defined as minor oozing from the wound incision controlled with compressive gauze only -2: moderate bleeding associated with the presence of large clots continuously disrupting the surgical area and requiring additional hemostatic measures; -3: severe bleeding requiring further medical control of coagulation

  Within the first 5 days post-surgery

• Number of presence of intraoral hematomas events

  changes in mucosa color and edema (recorded as a dichotomous variable- yes/no).

  On day 7 post-surgery

• Number of presence of extraoral hematomas events

  changes in skin color and edema (recorded as a dichotomous variable- yes/no).

  On day 7 post-surgery

Study Arms (4)

Control group (Cg)

ACTIVE COMPARATOR

The control group (Cg) comprised 20 procedures performed in patients not on OAT. Buccal and palatal-lingual flaps were repositioned and sutured with simple stitches using 5/0 monofilament nylon yarn, and a dry gauze was applied for 30 minutes.

Procedure: Dental implant surgery

Tranexamic acid group (TXAg)

EXPERIMENTAL

TXAg group comprised 20 procedures performed in patients OAT. Buccal and palatal-lingual flaps were repositioned and sutured as in the Cg plus compression on the wound for 30 minutes using a gauze soaked in the contents of a 500mg ampoule of TXA, after which a new gauze soaked in the contents of a 500mg ampoule of TXA was applied for two hours.

Procedure: Dental implant surgery

Bismuth subgallate group (BSg)

EXPERIMENTAL

BSg group comprised 20 procedures performed in patients OAT. At the moment of surgery, the contents of an anestube (1.8 ml) were mixed with a sufficient amount of BS powder to obtain a paste similar in consistency to tooth-paste (29). A thin layer of the paste was applied on the bone ridge, and buccal and palatal-lingual flaps were then repositioned and sutured as in the Cg. compression on the wound with a dry gauze for 30 minutes, after which a new dry gauze was placed for another two hours.

Procedure: Dental implant surgery

Dry gauze group (DGg)

EXPERIMENTAL

DGg group comprised 20 procedures performed in patients OAT. Buccal and palatal-lingual flaps were repositioned and sutured as in the Cg plus compression on the wound with a dry gauze for 30 minutes, after which a new dry gauze was placed for another two hours.

Procedure: Dental implant surgery

Interventions

Dental implant surgery PROCEDURE

Bismuth subgallate group (BSg); Control group (Cg); Dry gauze group (DGg); Tranexamic acid group (TXAg)

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects:
• Systemically healthy.
• Healthy periodontal tissues or well-controlled periodontal health.
• In need of a maximum of two dental implants per hemiarcade,
• Showing ≥8mm bone height and ≥6 horizontal bone width.
• Needing a maximum of two surgical procedures.
• Who had written consent from the referring service to undergo the surgical procedure.

You may not qualify if:

• Subjects:
• Requiring implant placement immediately after extraction.
• Systemic disease contraindicating implant surgery.
• Mental disability preventing them from complying with the protocol.
• Hematological, metabolic, autoimmune or bone diseases.
• Hepatic alterations or receiving medication affecting liver function.
• Receiving corticoid therapy, chemotherapy, or anticoagulant therapy within 10 days prior to the surgery.
• Taking antibiotics that interact with oral anticoagulants.
• Requiring vertical or periosteal incisions.
• Requiring bone regeneration strategy.
• When treatment involved placing an implant in more than one hemiarcade, the corresponding surgeries were scheduled 30 days apart.

Sponsors & Collaborators

• Jorge Ernesto Aguilar: lead

Study Sites (1)

Masters in Dental Implantology (MIO) program at the University of Salvador (USAL)-Argentine Dental Association

Buenos Aires, 1125, Argentina

Location

Related Publications (48)

• Keeling D, Baglin T, Tait C, Watson H, Perry D, Baglin C, Kitchen S, Makris M; British Committee for Standards in Haematology. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol. 2011 Aug;154(3):311-24. doi: 10.1111/j.1365-2141.2011.08753.x. Epub 2011 Jun 14. No abstract available.

  PMID: 21671894 BACKGROUND

• van Diermen DE, van der Waal I, Hoogvliets MW, Ong FN, Hoogstraten J. Survey response of oral and maxillofacial surgeons on invasive procedures in patients using antithrombotic medication. Int J Oral Maxillofac Surg. 2013 Apr;42(4):502-7. doi: 10.1016/j.ijom.2012.09.018. Epub 2012 Nov 2.

  PMID: 23123097 RESULT

• Caliskan M, Tukel HC, Benlidayi ME, Deniz A. Is it necessary to alter anticoagulation therapy for tooth extraction in patients taking direct oral anticoagulants? Med Oral Patol Oral Cir Bucal. 2017 Nov 1;22(6):e767-e773. doi: 10.4317/medoral.21942.

  PMID: 29053656 RESULT

• Madrid C, Sanz M. What influence do anticoagulants have on oral implant therapy? A systematic review. Clin Oral Implants Res. 2009 Sep;20 Suppl 4:96-106. doi: 10.1111/j.1600-0501.2009.01770.x.

  PMID: 19663955 RESULT

• Mehra P, Cottrell DA, Bestgen SC, Booth DF. Management of heparin therapy in the high-risk, chronically anticoagulated, oral surgery patient: a review and a proposed nomogram. J Oral Maxillofac Surg. 2000 Feb;58(2):198-202. doi: 10.1016/s0278-2391(00)90339-2.

  PMID: 10670599 RESULT

• George C, Barras M, Coombes J, Winckel K. Unfractionated heparin dosing in obese patients. Int J Clin Pharm. 2020 Apr;42(2):462-473. doi: 10.1007/s11096-020-01004-5. Epub 2020 Mar 5.

  PMID: 32140914 RESULT

• Daniels PR. Peri-procedural management of patients taking oral anticoagulants. BMJ. 2015 Jul 14;351:h2391. doi: 10.1136/bmj.h2391.

  PMID: 26174061 RESULT

• Halpern LR, Adams DR, Clarkson E. Treatment of the Dental Patient with Bleeding Dyscrasias: Etiologies and Management Options for Surgical Success in Practice. Dent Clin North Am. 2020 Apr;64(2):411-434. doi: 10.1016/j.cden.2019.12.010. Epub 2020 Jan 31.

  PMID: 32111278 RESULT

• Dewan K, Bishop K, Muthukrishnan A. Management of patients on warfarin by general dental practitioners in South West Wales: continuing the audit cycle. Br Dent J. 2009 Feb 28;206(4):E8; discussion 214-5. doi: 10.1038/sj.bdj.2009.112. Epub 2009 Feb 13.

  PMID: 19214196 RESULT

• Suresh V, Bishawi M, Manning MW, Patel C, Rogers J, Milano C, Schroder J, Daneshmand M, Powers D. Management of Patients With Left Ventricular Assist Devices Requiring Teeth Extraction: Is Halting Anticoagulation Appropriate? J Oral Maxillofac Surg. 2018 Sep;76(9):1859-1863. doi: 10.1016/j.joms.2017.10.022. Epub 2017 Oct 31.

  PMID: 29156176 RESULT

• Kammerer PW, Frerich B, Liese J, Schiegnitz E, Al-Nawas B. Oral surgery during therapy with anticoagulants-a systematic review. Clin Oral Investig. 2015 Mar;19(2):171-80. doi: 10.1007/s00784-014-1366-3. Epub 2014 Nov 22.

  PMID: 25413495 RESULT

• Lopez MA, Andreasi Bassi M, Confalone L, Gaudio RM, Lombardo L, Lauritano D. Clinical outcome of 215 transmucosal implants with a conical connection: a retrospective study after 5-year follow-up. J Biol Regul Homeost Agents. 2016 Apr-Jun;30(2 Suppl 1):55-60.

  PMID: 27469549 RESULT

• Ascani A, Iorio A, Agnelli G. Withdrawal of warfarin after deep vein thrombosis: effects of a low fixed dose on rebound thrombin generation. Blood Coagul Fibrinolysis. 1999 Jul;10(5):291-5.

  PMID: 10456621 RESULT

• Doonquah L, Mitchell AD. Oral surgery for patients on anticoagulant therapy: current thoughts on patient management. Dent Clin North Am. 2012 Jan;56(1):25-41, vii. doi: 10.1016/j.cden.2011.06.002.

  PMID: 22117941 RESULT

• Garcia DA, Regan S, Henault LE, Upadhyay A, Baker J, Othman M, Hylek EM. Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med. 2008 Jan 14;168(1):63-9. doi: 10.1001/archinternmed.2007.23.

  PMID: 18195197 RESULT

• Akopov SE, Suzuki S, Fredieu A, Kidwell CS, Saver JL, Cohen SN. Withdrawal of warfarin prior to a surgical procedure: time to follow the guidelines? Cerebrovasc Dis. 2005;19(5):337-42. doi: 10.1159/000085027. Epub 2005 Apr 8.

  PMID: 15818034 RESULT

• Wahl MJ. Dental surgery in anticoagulated patients. Arch Intern Med. 1998 Aug 10-24;158(15):1610-6. doi: 10.1001/archinte.158.15.1610.

  PMID: 9701094 RESULT

• Wahl MJ. Demystifying medical complexities. J Calif Dent Assoc. 2000 Jul;28(7):510-8.

  PMID: 11324133 RESULT

• 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.

  PMID: 26592859 RESULT

• Weltman NJ, Al-Attar Y, Cheung J, Duncan DP, Katchky A, Azarpazhooh A, Abrahamyan L. MANAGEMENT OF DENTAL EXTRACTIONS IN PATIENTS TAKING WARFARIN AS ANTICOAGULANT TREATMENT: A SYSTEMATIC REVIEW. J Can Dent Assoc. 2015;81:f20.

  PMID: 26679334 RESULT

• Cai J, Ribkoff J, Olson S, Raghunathan V, Al-Samkari H, DeLoughery TG, Shatzel JJ. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. Eur J Haematol. 2020 Feb;104(2):79-87. doi: 10.1111/ejh.13348. Epub 2019 Dec 16.

  PMID: 31729076 RESULT

• Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev. 2013 Jul 23;2013(7):CD010562. doi: 10.1002/14651858.CD010562.pub2.

  PMID: 23881695 RESULT

• Cankaya D, Dasar U, Satilmis AB, Basaran SH, Akkaya M, Bozkurt M. The combined use of oral and topical tranexamic acid is a safe, efficient and low-cost method in reducing blood loss and transfusion rates in total knee arthroplasty. J Orthop Surg (Hong Kong). 2017 Jan;25(1):2309499016684725. doi: 10.1177/2309499016684725.

  PMID: 28176599 RESULT

• Perdigao JP, de Almeida PC, Rocha TD, Mota MR, Soares EC, Alves AP, Sousa FB. Postoperative bleeding after dental extraction in liver pretransplant patients. J Oral Maxillofac Surg. 2012 Mar;70(3):e177-84. doi: 10.1016/j.joms.2011.10.033.

  PMID: 22374059 RESULT

• Ockerman A, Vanhaverbeke M, Miclotte I, Belmans A, Vanassche T, Politis C, Jacobs R, Verhamme P. Tranexamic acid to reduce bleeding after dental extraction in patients treated with non-vitamin K oral anticoagulants: design and rationale of the EXTRACT-NOAC trial. Br J Oral Maxillofac Surg. 2019 Dec;57(10):1107-1112. doi: 10.1016/j.bjoms.2019.10.297. Epub 2019 Oct 25.

  PMID: 31669068 RESULT

• Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother. 2006 Dec;40(12):2205-10. doi: 10.1345/aph.1H295. Epub 2006 Nov 7.

  PMID: 17090725 RESULT

• Couto EV, Ballin CR, Sampaio CP, Maeda CA, Ballin CH, Dassi CS, Miura LY. Experimental study on the effects of bismuth subgallate on the inflammatory process and angiogenesis of the oral mucosa. Braz J Otorhinolaryngol. 2016 Jan-Feb;82(1):17-25. doi: 10.1016/j.bjorl.2014.12.009. Epub 2015 Oct 27.

  PMID: 26614041 RESULT

• Thorisdottir H, Ratnoff OD, Maniglia AJ. Activation of Hageman factor (factor XII) by bismuth subgallate, a hemostatic agent. J Lab Clin Med. 1988 Oct;112(4):481-6.

  PMID: 3171356 RESULT

• Maniglia AJ, Kushner H, Cozzi L. Adenotonsillectomy. A safe outpatient procedure. Arch Otolaryngol Head Neck Surg. 1989 Jan;115(1):92-4. doi: 10.1001/archotol.1989.01860250094034.

  PMID: 2909235 RESULT

• Radoi L, Hajage D, Giboin C, Maman L, Monnet-Corti V, Descroix V, Mahe I. Perioperative management of oral anticoagulated patients undergoing an oral, implant, or periodontal procedure: a survey of practices of members of two dental scientific societies, the PRADICO study. Clin Oral Investig. 2019 Dec;23(12):4311-4323. doi: 10.1007/s00784-019-02877-1. Epub 2019 Mar 19.

  PMID: 30887189 RESULT

• Bacci C, Berengo M, Favero L, Zanon E. Safety of dental implant surgery in patients undergoing anticoagulation therapy: a prospective case-control study. Clin Oral Implants Res. 2011 Feb;22(2):151-6. doi: 10.1111/j.1600-0501.2010.01963.x. Epub 2010 Oct 13.

  PMID: 20946205 RESULT

• Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, Bolger A, Cabell CH, Takahashi M, Baltimore RS, Newburger JW, Strom BL, Tani LY, Gerber M, Bonow RO, Pallasch T, Shulman ST, Rowley AH, Burns JC, Ferrieri P, Gardner T, Goff D, Durack DT; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007 Oct 9;116(15):1736-54. doi: 10.1161/CIRCULATIONAHA.106.183095. Epub 2007 Apr 19.

  PMID: 17446442 RESULT

• Sannino G, Cappare P, Montemezzi P, Alfieri O, Pantaleo G, Gherlone E. Postoperative bleeding in patients taking oral anticoagulation therapy after 'All-on-four' rehabilitation: A case-control study. Int J Oral Implantol (Berl). 2020;13(1):77-87.

  PMID: 32186289 RESULT

• Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuunemann HJ; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):7S-47S. doi: 10.1378/chest.1412S3. No abstract available.

  PMID: 22315257 RESULT

• Zanon E, Martinelli F, Bacci C, Cordioli G, Girolami A. Safety of dental extraction among consecutive patients on oral anticoagulant treatment managed using a specific dental management protocol. Blood Coagul Fibrinolysis. 2003 Jan;14(1):27-30. doi: 10.1097/00001721-200301000-00006.

  PMID: 12544725 RESULT

• Broekema FI, van Minnen B, Jansma J, Bos RR. Risk of bleeding after dentoalveolar surgery in patients taking anticoagulants. Br J Oral Maxillofac Surg. 2014 Mar;52(3):e15-9. doi: 10.1016/j.bjoms.2014.01.006. Epub 2014 Jan 30.

  PMID: 24485810 RESULT

• Di Minno A, Frigerio B, Spadarella G, Ravani A, Sansaro D, Amato M, Kitzmiller JP, Pepi M, Tremoli E, Baldassarre D. Old and new oral anticoagulants: Food, herbal medicines and drug interactions. Blood Rev. 2017 Jul;31(4):193-203. doi: 10.1016/j.blre.2017.02.001. Epub 2017 Feb 5.

  PMID: 28196633 RESULT

• Schmitt CM, Rusche B, Clemm R, Neukam FW, Buchbender M. Management of anticoagulated patients in dentoalveolar surgery: a clinical comparative study. Clin Oral Investig. 2020 Aug;24(8):2653-2662. doi: 10.1007/s00784-019-03124-3. Epub 2019 Nov 12.

  PMID: 31713746 RESULT

• Soares EC, Costa FW, Bezerra TP, Nogueira CB, de Barros Silva PG, Batista SH, Sousa FB, Sa Roriz Fonteles C. Postoperative hemostatic efficacy of gauze soaked in tranexamic acid, fibrin sponge, and dry gauze compression following dental extractions in anticoagulated patients with cardiovascular disease: a prospective, randomized study. Oral Maxillofac Surg. 2015 Jun;19(2):209-16. doi: 10.1007/s10006-014-0479-9. Epub 2014 Dec 21.

  PMID: 25528251 RESULT

• Ferrieri GB, Castiglioni S, Carmagnola D, Cargnel M, Strohmenger L, Abati S. Oral surgery in patients on anticoagulant treatment without therapy interruption. J Oral Maxillofac Surg. 2007 Jun;65(6):1149-54. doi: 10.1016/j.joms.2006.11.015.

  PMID: 17517299 RESULT

• Kim SH, Tramontina VA, Papalexiou V, Luczyszyn SM. Bismuth subgallate as a topical hemostatic agent at palatal donor sites. Quintessence Int. 2010 Sep;41(8):645-649.

  PMID: 20657853 RESULT

• Callanan V, Curran AJ, Smyth DA, Gormley PK. The influence of bismuth subgallate and adrenaline paste upon operating time and operative blood loss in tonsillectomy. J Laryngol Otol. 1995 Mar;109(3):206-8. doi: 10.1017/s0022215100129706.

  PMID: 7745335 RESULT

• Scully C, Hobkirk J, Dios PD. Dental endosseous implants in the medically compromised patient. J Oral Rehabil. 2007 Aug;34(8):590-9. doi: 10.1111/j.1365-2842.2007.01755.x.

  PMID: 17650169 RESULT

• Diz P, Scully C, Sanz M. Dental implants in the medically compromised patient. J Dent. 2013 Mar;41(3):195-206. doi: 10.1016/j.jdent.2012.12.008. Epub 2013 Jan 11.

  PMID: 23313715 RESULT

• Proietti R, Porto I, Levi M, Leo A, Russo V, Kalfon E, Biondi-Zoccai G, Roux JF, Birnie DH, Essebag V. Risk of pocket hematoma in patients on chronic anticoagulation with warfarin undergoing electrophysiological device implantation: a comparison of different peri-operative management strategies. Eur Rev Med Pharmacol Sci. 2015 Apr;19(8):1461-79.

  PMID: 25967723 RESULT

• Bajkin BV, Urosevic IM, Stankov KM, Petrovic BB, Bajkin IA. Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment. Br J Oral Maxillofac Surg. 2015 Jan;53(1):39-43. doi: 10.1016/j.bjoms.2014.09.009. Epub 2014 Oct 11.

  PMID: 25311541 RESULT

• DeClerck D, Vinckier F, Vermylen J. Influence of anticoagulation on blood loss following dental extractions. J Dent Res. 1992 Feb;71(2):387-90. doi: 10.1177/00220345920710020701.

  PMID: 1532608 RESULT

• Dunn AS, Turpie AG. Perioperative management of patients receiving oral anticoagulants: a systematic review. Arch Intern Med. 2003 Apr 28;163(8):901-8. doi: 10.1001/archinte.163.8.901.

  PMID: 12719198 RESULT

Study Officials

• Jorge Aguilar, Chair Prof

  Universidad del Salvador

  STUDY DIRECTOR

• Mariano Vassallo, Assoc Prof

  Universidad del Salvador

  PRINCIPAL INVESTIGATOR

• Jose Zamberlin, Assoc Prof

  Universidad del Salvador

  PRINCIPAL INVESTIGATOR

• Marina Diaz Roig, Assist Prof

  Universidad del Salvador

  PRINCIPAL INVESTIGATOR

• Ricardo Macchi, Chair Prof

  University of Buenos Aires

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The participants on OAT allocated to one of the three different local hemostatic strategies, were not informed wich agent was used. Time of compression was equal in all groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director and Professor, Oral Implantology Program

Model Details: 80 surgical procedures (pr) in 71 patients (18 not OAT/53 on OAT) were assigned to one of four groups: control group (Cg n=20 pr not OAT) and 3 experimental groups of patients on OAT with local hemostatic management were randomized: tranexamic acid group (TXAg n=20 pr), bismuth subgallate group (BSg n=20 pr) and dry gauze group (DGg n=20 pr).

Study Record Dates

• First Submitted: April 11, 2021
• First Posted: April 15, 2021
• Study Start: March 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: June 1, 2019
• Last Updated: October 12, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1)