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CADTH RAPID RESPONSE REPORT: SUMMARY WITH CRITICAL APPRAISAL Endodontic Therapy Interventions for Root Canal Failure in Permanent Dentition: A Review of Clinical Effectiveness, Cost- Effectiveness, and Guidelines Service Line: Rapid Response Service Version: 1.0 Publication Date: March 08, 2017 Report Length: 9 Pages

Author: Chuong Ho, Charlene Argáez Cite As: Endodontic therapy interventions for root canal failure in permanent dentition: A review of clinical effectiveness, cost-effectiveness, and guidelines. Ottawa: CADTH; 2017 Mar. (CADTH rapid response report: summary with critical appraisal). ISSN: 1922-8147 (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH. CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the contents of this document or any of the source materials. This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites. Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada s federal, provincial, or territorial governmentsor any third party supplier of information. This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user s own risk. This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada. The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors. About CADTH: CADTH is an independent, not-for-profit organization responsible for providing Canada s health care decision-makers with objective evidence to help make informed decisions about the optimal use of drugs, medical devices, diagnostics, and procedures in our health care system. Funding: CADTH receives funding from Canada s federal, provincial, and territorial governments, with the exception of Quebec. SUMMARY WITH CRITICAL APPRAISAL Endodontic Retreatment for Root Canal Failure 2

Context and Policy Issues Root canal, or endodontic treatment, is a procedure in which an inflamed or infected pulp is removed, and the inside of the tooth is cleaned, disinfected, then filled and sealed with a restorative material. The procedure has a high success rate, although persistence of symptoms or infection recurrence can occur in 10% to 15% of cases. 1 Tooth survival over two to 10 years following initial root canal treatment was shown in a systematic review to range between 86% and 93%. 2 In many cases of infection or symptom recurrence, a second root canal treatment (root canal retreatment) is considered. Apicoectomy is usually needed when root canal retreatment is not successful, and is a procedure in which the root tip, or apex, is removed along with the infected tissue, then a root end filling (retrofilling) is placed to seal the area. 3 Factors associated with a better chance of success of apicoectomy include patients 45 years old, upper anterior or premolar teeth, cases without preoperative pain, lesions without periodontal involvement, absence of perforating lesions, and teeth with only one periapical surgery. 4-6 In the case of apicoectomy failure, the tooth may need to be extracted. This Rapid Response report aims to review the clinical and cost-effectiveness of endodontic interventions (root canal re-treatment, apicoectomy and retrofilling) after failed root canal treatment, compared to initial root canal treatment alone (no treatment) or tooth extraction. Guidelines associated with the use of root canal retreatment, apicoectomy with or without apical curettage, and retrofilling in permanent teeth will also be examined. Research Question 1. What is the clinical effectiveness of root-canal re-treatment in permanent teeth after failed root canal treatment compared to initial root canal treatment alone (i.e. no treatment) or tooth extraction? 2. What is the clinical effectiveness of apicoectomy with or without apical curettage in permanent teeth after failed root canal treatment compared to initial root canal treatment alone (i.e. no treatment) or tooth extraction? 3. What is the clinical effectiveness of retrofilling in permanent teeth after failed root canal treatment compared to initial root canal treatment alone (i.e. no treatment) or tooth extraction? 4. What is the cost-effectiveness of root-canal re-treatment in permanent teeth after failed root canal treatment compared to initial root canal treatment alone (i.e. no treatment) or tooth extraction? 5. What is the cost-effectiveness of apicoectomy with or without apical curettage in permanent teeth after failed root canal treatment compared to initial root canal treatment alone (i.e. no treatment) or tooth extraction? 6. What is the cost-effectiveness of retrofilling in permanent teeth after failed root canal treatment compared to initial root canal treatment alone (i.e. no treatment) or tooth extraction? SUMMARY WITH CRITICAL APPRAISAL Endodontic Retreatment for Root Canal Failure 3

7. What are the evidence-based guidelines regarding the use of root canal retreatment, apicoectomy with or without apical curettage, and retrofilling in permanent teeth? Table 1: Selection Criteria Population Methods Literature Search Methods A limited literature search was conducted on key resources including PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, economic studies, randomized controlled trials, non-randomized studies, and guidelines. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2007 and February 7, 2017. Rapid Response reports are organized so that the evidence for each research question is presented separately. Selection Criteria and Methods One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1. Children and adults (all ages) with permanent teeth, presenting with root canal treatment failure Intervention Comparator Outcomes Subgroups of interest: Indigenous populations Root canal re-treatment Apicoectomy with or without apical curettage Retrofilling Initial root canal treatment alone; tooth extraction (No comparator required for guidelines) Treatment success rate, clinical benefits and harms (e.g., pain, infection, root fracture, root perforation) Cost-effectiveness outcomes (e.g., cost per health benefit/qaly) Study Designs Evidence-based guidelines, including indications for use Health technology assessments (HTA), systematic reviews (SR), meta-analyses (MA), randomized controlled trials (RCTs), non-rcts, economic evaluations, guidelines. SUMMARY WITH CRITICAL APPRAISAL Endodontic Retreatment for Root Canal Failure 4

Exclusion Criteria Articles were excluded if they did not meet the selection criteria outlined in Table 1, they were duplicate publications, or were published prior to 2007. Quantity of Research Available A total of 656 citations were identified in the literature search. Following screening of titles and abstracts, 639citations were excluded and 17 potentially relevant reports from the electronic search were retrieved for full-text review. Two potentially relevant publications were retrieved from the grey literature search. Of these potentially relevant articles, 19 publications were excluded for various reasons, and no publications met the inclusion criteria and were included in this report. Appendix 1 describes the PRISMA flowchart of the study selection. Additional references of potential interest that did not meet the selection criteria are provided in Appendix 2. Summary of Findings No evidence was identified regarding the clinical and cost effectiveness of endodontic interventions following a failed root canal treatment. No evidence-based guidelines for endodontic re-treatment were identified. Conclusions and Implications for Decision or Policy Making There was no evidence found on the clinical and cost-effectiveness of endodontic interventions (root canal re-treatment, apicoectomy and retrofilling) after failed root canal treatment, compared to initial root canal treatment alone (no treatment) or tooth extraction. There were no guidelines found associated with the use of root canal retreatment, apicoectomy with or without apical curettage, and retrofilling in permanent teeth. The literature search identified some studies with potential interest which reported the clinical effectiveness of root canal re-treatment and apicoectomy with no comparator, or with a comparator which was not initial root canal treatment alone or tooth extraction. A list of these studies is provided in Appendix 2. A 2008 systematic review of longitudinal studies with a minimum of 6-month follow-up which investigated the success rates of root canal re-treatment found the rate of complete healing of the permanent tooth was 76.7%. 7 A systematic review of RCTs up to February 2016 compared the clinical effectiveness of the surgical (apicoectomy) or non-surgical (root canal re-treatment) approach for tooth healing, and found no evidence of superiority of either approach at one- year, four-year and 10-year follow-up. 8 This non-superiority was also reported by a 2015 systematic review of randomized and non-randomized studies that found no statistically significant difference in the long-term follow-up (more than four years) between the surgical and non-surgical approaches to retreatment. 9 A retrospective analysis based on German insurance claims data of 93,797 apicoectomies showed tooth cumulative survival rates of 91.4%, 85.7% and 81.6% at one year, two years and three years, respectively. 10 For comparison, retrospective data analysis based on German insurance claims data of 556,067 initial root canal treatments found the cumulative survival rate of 93.0%, 88.2% and 84.3% at one year, two years and three years, respectively. 11 A Canadian prospective study on the outcomes of apicoectomy on 134 teeth after a minimum of four years and up to 10 years after treatment showed 74% were healed and 94% were functional (without signs or symptoms). 12 The 5-year prognosis after apicoectomy was 8% poorer (75.9% SUMMARY WITH CRITICAL APPRAISAL Endodontic Retreatment for Root Canal Failure 5

healed) than at one year (83.8% healed) in a prospective study on 191 subjects. 13 In summary, these studies showed, for re-treatment following an initial root call, that the success rate for the non-surgical approach (root canal re-treatment) was over 76% at a minimum of 6 months follow-up, while the success rate for the surgical approach (apicoectomy) was over 81% after three-year follow-up. Comparisons between the retreatment with surgical and non-surgical approaches to re-treatment do not show superiority of either approach in long-term follow-up. SUMMARY WITH CRITICAL APPRAISAL Endodontic Retreatment for Root Canal Failure 6

References 1. Lieblich SE. Endodontic surgery. Dent Clin North Am. 2012 Jan;56(1):121-ix. 2. Ng YL, Mann V, Gulabivala K. Tooth survival following non-surgical root canal treatment: a systematic review of the literature. Int Endod J. 2010 Mar;43(3):171-89. 3. Colgate Professional [Internet]. New York: Colgate-Palmolive Company. Apicoectomy; 2017 [cited 2017 Feb 8]. Available from: http://www.colgateprofessional.com/patient-education/articles/apicoectomy 4. Serrano-Gimenez M, Sanchez-Torres A, Gay-Escoda C. Prognostic factors on periapical surgery: A systematic review. Med Oral Patol Oral Cir Bucal [Internet]. 2015 Nov 1 [cited 2017 Feb 8];20(6):e715-e722. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4670252 5. von Arx T, Penarrocha M, Jensen S. Prognostic factors in apical surgery with root-end filling: a meta-analysis. J Endod. 2010 Jun;36(6):957-73. 6. Christiansen R, Kirkevang LL, Horsted-Bindslev P, Wenzel A. Patient discomfort following periapical surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Feb;105(2):245-50. 7. Ng YL, Mann V, Gulabivala K. Outcome of secondary root canal treatment: a systematic review of the literature. Int Endod J. 2008 Dec;41(12):1026-46. 8. Del Fabbro M, Corbella S, Sequeira-Byron P, Tsesis I, Rosen E, Lolato A, et al. Endodontic procedures for retreatment of periapical lesions. Cochrane Database Syst Rev. 2016 Oct 19;10:CD005511. 9. Kang M, In JH, Song M, Kim SY, Kim HC, Kim E. Outcome of nonsurgical retreatment and endodontic microsurgery: a meta-analysis. Clin Oral Investig. 2015 Apr;19(3):569-82. 10. Raedel M, Hartmann A, Bohm S, Walter MH. Three-year outcomes of apicectomy (apicoectomy): Mining an insurance database. J Dent. 2015 Oct;43(10):1218-22. 11. Raedel M, Hartmann A, Bohm S, Walter MH. Three-year outcomes of root canal treatment: Mining an insurance database. J Dent. 2015 Apr;43(4):412-7. 12. Barone C, Dao TT, Basrani BB, Wang N, Friedman S. Treatment outcome in endodontics: the Toronto study--phases 3, 4, and 5: apical surgery. J Endod. 2010 Jan;36(1):28-35. 13. von Arx T, Jensen SS, Hanni S, Friedman S. Five-year longitudinal assessment of the prognosis of apical microsurgery. J Endod. 2012 May;38(5):570-9. SUMMARY WITH CRITICAL APPRAISAL Endodontic Retreatment for Root Canal Failure 7

Appendix 1: Selection of Included Studies 656 citations identified from electronic literature search and screened 639 citations excluded 17 potentially relevant articles retrieved for scrutiny (full text, if available) 2 potentially relevant reports retrieved from other sources (grey literature, hand search) 19 potentially relevant reports 19 reports excluded: -irrelevant comparator (14) -other (review articles)(5) 0 reports included in review SUMMARY WITH CRITICAL APPRAISAL Endodontic Retreatment for Root Canal Failure 8

Appendix 2: Additional References of Potential Interest (studies that compared different retreatment approaches) Systematic reviews Ng YL, Mann V, Gulabivala K. Outcome of secondary root canal treatment: a systematic review of the literature. Int Endod J [Internet]. 2008 Dec [cited 2017 Mar 7];41(12):1026-1046. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19133093 Kang M, In Jung H, Song M, Kim SY, Kim HC, Kim E. Outcome of nonsurgical retreatment and endodontic microsurgery: a metaanalysis. Clin Oral Invest [Internet]. 2015 Apr [cited 2017 Mar 7];19(3):569-582. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25595864 Del Fabbro M, Corbella S, Sequeira-Byron P, Tsesis I, Rosen E, Lolato A, et al. Endodontic procedures for retreatment of periapical lesions. Cochrane Database Syst Rev; 2016 Oct 19: CD005511. Studies von AT, Jensen SS, Hanni S, Friedman S. Five-year longitudinal assessment of the prognosis of apical microsurgery. J Endod.2012 May;38(5):570-9. Tawil PZ, Saraiya VM, Galicia JC, Duggan DJ. Periapical microsurgery: the effect of root dentinal defects on short- and long-term outcome. J Endod.2015 Jan;41(1):22-7 Shinbori N, Grama AM, Patel Y, Woodmansey K, He J. Clinical outcome of endodontic microsurgery that uses EndoSequence BC root repair material as the root-end filling material. J Endod.2015 May;41(5):607-12. Caliskan MK, Tekin U, Kaval ME, Solmaz MC. The outcome of apical microsurgery using MTA as the root-end filling material: 2- to 6-year follow-up study. IntEndod J.2016 Mar;49(3):245-54. Raedel M, Hartmann A, Bohm S, Walter MH. Three-year outcomes of apicectomy (apicoectomy): Mining an insurance database. J Dent.2015 Oct;43(10):1218-22. Kruse C, Spin-Neto R, Christiansen R, Wenzel A, Kirkevang LL. Periapical Bone Healing after Apicectomy with and without retrograde root filling with mineral trioxide aggregate: A 6-year Follow-up of a Randomized Controlled Trial. J Endod.2016 Apr;42(4):533-7. Barone C, Dao TT, Basrani BB, Wang N, Friedman S. Treatment outcome in endodontics: the Toronto study--phases 3, 4, and 5: apical surgery. J Endod.2010 Jan;36(1):28-35. Taschieri S, Corbella S. Teeth treated with apicoectomies had acceptable 3-year survival rates, based on insurance claims data. J Evid Based Dent Pract.2016 Sep;16(3):193-5. Raedel M, Hartmann A, Bohm S, Walter MH. Three-year outcomes of root canal treatment: Mining an insurance database. J Dent.2015 Apr;43(4):412-7. SUMMARY WITH CRITICAL APPRAISAL Endodontic Retreatment for Root Canal Failure 9