Clinical outcome of guided endodontics versus freehand drilling: A controlled clinical trial, single arm with external control group
Pulp canal obliteration (PCO) is a process characterized by the deposition of hard tissue within the root canal (Langeland et al., ). It presents most commonly as a sequelae of traumatic dental injuries (TDI) and is reported to develop more often in teeth following concussion and subluxation injuries (Oginni & Adekoya‐Sofowora, ). It can also present as a result of caries, tooth surface loss or operative procedures and rarely orthodontic treatment (Langeland et al., ). Also, in elderly patients, a lifelong apposition of secondary or tertiary dentin can end up in a severe PCO (Kiefner et al., ). Traumatic dental injuries are highly common and account for 85% of patients presenting with injuries to the oral region. They affect one billion people globally with a prevalence of 15.2% in permanent dentition (Petti et al., ). Most often, patients suffering from TDI in the past and present years after the accident with a single discoloured tooth. This discolouration may be the result of PCO, the pulp cavity being filled with dark tertiary dentine resulting in a darker hue, loss of translucency and yellowish appearance of the crown which is detected clinically (McCabe & Dummer, ; Oginni & Adekoya‐Sofowora, ). Although the exact mechanism of PCO is still unknown, damage to the neurovascular supply of the pulp is probably related to this process (McCabe & Dummer, ; Robertson, ; Yaacob & Hamid, ). Furthermore, teeth presenting PCO after trauma could develop pulpal necrosis and apical periodontitis (AP) in a range from 1% up to 27% of the cases (Andreasen, ; Andreasen et al., ; Holcomb & Gregory Jr., ; Jacobsen & Kerekes, ; Oginni et al., ; Robertson et al., ; Stalhane & Hedegard, ). It is generally accepted that sensibility tests are unreliable in cases presenting with PCO (Holcomb & Gregory Jr., ; Robertson et al., , Oginni et al., ). Endodontic treatment of such cases should only be initiated if the tooth presents symptoms or radiographic signs of apical periodontitis (McCabe & Dummer, ). However, the negotiation of root canals presenting with PCO has been classified in the moderate to high‐risk category by the American Association of Endodontics (AAE, ), and in such cases, there is a higher probability of technical failure which can compromise the outcome of the root canal treatment (Cvek et al., ). In this regard, acquisition of limited field of view cone‐beam computed tomography (CBCT) can be beneficial. It allows for a three‐dimensional visualization of the root canal and a better understanding of the tooth's anatomy, such as the number of root canals and their exact location and orientation in the root (Patel et al., ). This allows the clinician to establish a customized strategy with which to approach the canal prior to treatment. Repeated intraoral radiographs can be then taken during treatment to verify the access cavity path. CBCT can also be beneficial for intra‐appointment identification and localization of calcified canals (Fayad et al., ; Floratos & Miltiadous, ; Quaresma et al., ). However, the acquisition of an extra CBCT volume for intra‐appointment localization of the canals involves longer treatment time and additional exposure to radiation for the patient. A current alternative for the treatment of PCO is the concept of “Guided Endodontics”, in which a 3D‐printed guide is used to guide the bur up to the target location (Krastl et al., ; van der Meer et al., ). It can reduce the risk for iatrogenic damage or excessive loss of tooth structure. Furthermore, the likelihood of finding the canal is increased, while reducing also treatment time (Buchgreitz et al., ; Connert et al., , ; Torres et al., ; Zehnder et al., ). Additionally, the outcome is not dependent on the operator's experience (Connert et al., , ; Torres et al., , ). Recently, a systematic review of the literature reported that guided endodontics is an effective and predictable tool for locating calcified root canals (Peña‐Bengoa et al., ). After analysis of the literature, the authors included a total of 21 case reports, 11 case series and 1 observational cohort study on 50 patients. However, although the studies were classified as having low risk of bias, a potential publication bias should be considered as well as the impact of non‐publication of failed cases (DeVito & Goldacre, ). Case reports are important when assessing new techniques where the success rate is not yet known or difficult to estimate (Peña‐Bengoa et al., ). Nevertheless, high‐quality, prospective clinical studies are lacking. Such studies are needed to increase the evidence for guided endodontics (Connert et al., ; Peña‐Bengoa et al., ). Therefore, the aim of this controlled clinical trial is to assess the clinical outcome of guided endodontics for the treatment of teeth presenting with PCO in comparison with freehand treatment. The main clinical research question is (PICO): in teeth presenting with PCO (P), does guided endodontics treatment (I) results in less technical failures (O) compared to freehand treatment (C)? 

This clinical trial has been written according to Preferred Reporting Items for Randomized Trials in Endodontics (PRIRATE) 2020 guidelines (Nagendrababu et al., ). Study design The study was designed as a controlled clinical trial (CCT): Single arm trial, prospective, nonrandomized, single‐centre study with an external control group. The design was structured according to the ethical principles of the Declaration of Helsinki and Good Clinical Practice (GCP). The treatment of patients with guided endodontics has been approved by the Ethics Committee of the University Hospitals Leuven, Leuven, Belgium (S64630). Written informed consent was obtained prior to starting the treatment. Additionally, all participants received a verbal explanation in terms suited to their comprehension of the purposes, procedures and potential risks of the study and of their rights as research participants. The Principal Investigator (AT) assured that no deviation from, or changes to the protocol were made except where necessary to eliminate an immediate hazard(s) to the trial participants. The trial was registered in the ISRCTN registry (ISRCTN75277265, https://www.isrctn.com ). Patient selection Between April 2018 and October 2022, all patients referred for endodontic treatment at the Endodontic Department at the University Hospitals of Leuven, Leuven, Belgium were screened for eligibility during the initial consultation. The inclusion criteria were as follows: Tooth presenting with PCO, and Symptoms and/or radiographic signs of apical periodontitis (AP). All patients had a thorough intraoral examination. A periapical radiograph was taken for assessment. If the tooth presented PCO, a score was given based on the visibility of the canal on the periapical radiograph as: (1) root canal not visible (total PCO), (2) root canal visible up to apical root third, (3) root canal visible up to middle root third, (4) root canal visible up to coronal root third. Then, a pre‐operative CBCT scan was taken for further assessment using the NewTom VGi evo (Cefla, Imola, Italy) operating at 110 kVp and 3 mA. If the CBCT volume confirmed the initial diagnosis of PCO, and the clinician evaluated the case as being of high difficulty (AAE, ), patients were candidates for inclusion. The exclusion criteria were: Patients unwilling or unable to comply with the endodontic treatment. Tooth in need of extraction, or with an unfavourable prognosis. Sample size The sample size was calculated based on the probability of technical failure (perforation or canal not found) when drilling freehanded on teeth presenting PCO. Cvek et al.  reported a probability of technical failure (root canal not found or perforation) of 14.3% (7 out of 49 teeth) when drilling freehanded on anterior teeth with reduced pulpal lumen. Based on this data, a sample size calculation was performed with a power of 80% and a significance level of .05. Considering that the technical failure of guided endodontics was not known, an arbitrary technical failure rate of 2% was set to be clinically relevant. This would imply more than 10% improvement than drilling without guidance. The sample size was calculated by the normal approximation to the comparison of proportions using the TrialSize library from R in an iterative way, in which, for a new calculation, quantiles from an Studentized t‐distribution were used, for which the degrees of freedom corresponded to the requested number of data from the previous calculation. According to the test, a sample size of 59 teeth was needed. This was rounded up to 60 teeth (Figure ). Randomization and blinding Considering that 21 case reports, 11 case series and 1 observational cohort study on 50 patients (Peña‐Bengoa et al., ) show that the use of guides for endodontic treatment offers a highly predictable outcome, with a low risk of iatrogenic damage, randomizing the treatments was not considered to be ethical as it would not guarantee the best quality standards of treatment to the patient (AAE, ). As a result, an external (historical) control group was selected to assess the success rate of guided endodontics treatment. Blinding of the operator was not possible due to the study design. Control group A database search was carried out in the clinical management software (KWS, version 3.4.1, IT‐dienst UZ Leuven, Leuven, Belgium), for clinical records from the Endodontic Department at the University Hospitals of Leuven, Leuven, Belgium, on patients that were treated without the use of any guiding system between January 2014 and up October 2022. The following search terms were used to search on all consultation reports from the clinical database of the department of Endodontics: “calcified” OR “calcification” OR “obliterated” OR “obliteration” OR “small” OR “narrow” OR “perforated” OR “perforation” OR “not found” OR “not visible”. After the search was completed, a second operator not related to the clinical treatments (MD) analysed all dental reports and selected the patients for the control group. Patients presenting with all the following inclusion criteria were selected for inclusion: The patient was treated by a specialist in endodontics. A dental microscope was used. A CBCT was available before treatment. The tooth presented PCO visible on a periapical radiograph. The case can be classified as being of high difficulty (AAE, ). Symptoms and/or radiographic signs of AP were present at the time of treatment. Planning and guide design A pre‐operative CBCT (NewTom VGi evo, Cefla) and an intraoral scan (IOS) (Trios, 3Shape, Copenhagen, Denmark) were taken for every patient selected for guided endodontics treatment. The DICOM images from the CBCT and STL files from the IOS were imported into Mimics Medical software 23.0 (Materialize, Leuven, Belgium). Then the upper or lower jaw, depending on the case, was segmented using the threshold tool, and a 3D model was created. The registration of the IOS to the segmented CBCT model was first performed by using a 3‐point registration method to approximate both structures. Subsequently, the automatic global registration tool was applied and repeated for final registration until no further movement was possible. The correct registration was confirmed visually by checking the contour of the registered IOS on the CBCT images (Figure ). A path for the bur was created maintaining a straight‐line access up to the root canal. Special attention was placed to avoid drilling on the incisal border or buccal side of the tooth when possible. Then, the registered IOS together with the planned trajectory was imported into 3‐matic medical software 14.0 (Materialize) where a tooth‐supported guide was designed (Figure ). After completion of the design, an insertion axis was defined, and the undercut zones were removed by the software's tool. Subsequently, the guide was 3D printed in a biocompatible material (MED 610, Stratasys, Eden Prairie, MN, USA) using the Objet Connex 350 3D printer (Stratasys) and finally, a metallic inner sleeve (REF M.27.28.D100L5, Steco, Steco System‐Technik, Hamburg, Germany) was bonded to the guide (Figure ). Guided endodontic treatment Guided root canal treatment was performed by the same operator (AT) on all patients, always adhering to the quality guidelines for endodontic treatment from the European Society of Endodontology (ESE, ). First, full rubber dam isolation was placed, with the extension of the isolation field being determined by the extension of the guide. The guide was then placed on the patient's teeth and checked to fit passively on the crowns. The correct fit was checked on both ends of the guide (Figure ). If needed, the interproximal interferences were removed manually from the guide until achieving a passive fit. The stability was checked visually by pressing on one side of the guide (left or right), if there was no movement on the opposite side, the guide was stable and treatment started. Two 1 mm diameter carbide burs with different lengths were available for guided treatment. One short with 21 mm working length and 35 mm total length (REF O.27.28.B044.051, Steco), and a longer one with 28 mm working length and 42 mm total length (REF O.27.28.B044.052, Steco). The decision to use a long or short drill was based upon the case. A new bur was used on every treatment. Before drilling, the entry point was marked with a mechanical pencil through the inner sleeve and enamel was removed by hand with a diamond bur. Then the access cavity was precisely drilled using the selected carbide bur (Steco) mounted on and a Blue W&H WE‐56 LED G handpiece (W&H, Bürmoos, Austria) operated at 20 000 rpm using a pumping movement (Figure ). During drilling, water was irrigated at the entrance of the sleeve using a Stropko Irrigator (Vista Apex, Racine, WI, USA). When the target point was reached, the tooth was examined under the dental microscope. Small size K‐Files (ISO 06 up to 10, Dentsply Sirona, Baillagues, Switzerland) were used initially to negotiate the canal, and after glide path was achieved with a size 15 K‐File (Dentsply Sirona), instrumentation of the canal was performed with Waveone Gold files (Dentsply Sirona) up to at least a medium size (size 35, .06 taper) as final working file. Apical patency was controlled during the whole treatment with a size 10 K‐File (Dentsply Sirona). During treatment, the root canal was rinsed with at least 20 mL of 5% NaOCl in combination with sonic activation using EDDY (VDW, Munich, Germany), then a final irrigation protocol was applied using EDDY and 17% EDTA, and a final rinse with 5% NaOCl. The root was dried using paper points and filled using a vertical compaction technique with warm gutta‐percha and an epoxy sealer (AH Plus sealer, Dentsply Sirona). The access cavity was then filled with composite, occlusion was controlled, and the restoration was polished. A periapical radiograph was taken after treatment and the patient was scheduled for recall after 1 year (Figure ). Freehanded treatment (control group) Root canal treatment was performed by a specialist in endodontics not related to the study working at the time at the Endodontic Department at the University Hospitals of Leuven, Leuven, Belgium. Endodontic treatment complied with the quality guidelines for endodontic treatment from the European Society of Endodontology (ESE, ). A dental microscope was used during the whole procedure, and a CBCT was available before treatment for planning and visual guidance during treatment. Outcome measurements During guided endodontic treatment the primary outcome was evaluated by the operator (AT) as: Canal found Canal not found Perforation As secondary outcome, the qualitative accuracy of the drill path was assessed based on the clinical data and divided into 3 groups (adapted from Buchgreitz et al.  (Figure ): Optimal precision: Drill path centred. Acceptable precision: Drill path peripherally or tangentially transported. A manual correction was needed to find the canal. Technical Failure: Perforation or canal not found. Additionally, the healing after root canal treatment was assessed clinically and radiologically, with periapical radiographs, at 1 year and yearly until periapical healing. A favourable outcome was defined as absence of pain, swelling and other symptoms, no sinus tract, no loss of function and radiological evidence of a normal periodontal ligament space around the root (ESE, ). In the same manner as the guided treatment group, the primary outcome of the endodontic treatment from the control group was classified and recorded as: Canal found Canal not found Perforation Pairing of teeth for statistical analysis The following variables were recorded on both treatment groups (guided treatment and control group) for matched pairing: Tooth number. Tooth type: Anterior; incisors and canines, Posterior; premolars and molars. Tooth length in mm (measured on CBCT slices with an axis perpendicular to the tooth). Canal depth in mm: distance in mm from incisal border or occlusal plane to the canal (measured on CBCT slices with an axis perpendicular to the tooth). Canal depth percentage: percentage calculated by dividing the canal depth by the tooth length. Teeth were first matched to a pair from the other group based on the same tooth number and similar canal depths or depth percentages. If no match was found, matching was performed on tooth type (anterior and posterior) and similar canal depths or depth percentages. Statistical analysis All statistical analysis was done in S+ software, version 8.0 (TIBCO Software, Palo Alto, CA, USA). A technical failure was defined by not finding the canal or having a perforation during treatment. The null hypothesis stated that; H 0 : there is no difference in technical failure between guided endodontics and freehanded treatment. Additionally, the alternative hypothesis stated that; H 1 : Guided endodontics presents less technical failures compared to freehanded treatment. An analysis including all data, without matching, was performed by a generalized linear model for binary data using a logit link function with the primary outcome (canal found or not found/perforation) as response variable and the technique (guided or freehanded) as explanatory variable. p ≤ .05 was considered statistically significant. Data were also matched based on tooth type and canal depth. The primary outcome (canal found or not found/perforation) was analysed by a generalized estimation equations analysis for binomial data. Data were considered to be clustered per pair of control and matched teeth. Only teeth for which a matched pair was found were included in the analysis. p ≤ .05 was considered statistically significant. Additionally, descriptive statistics on the study patient's demographics and healing after root canal treatment were performed. 

The study was designed as a controlled clinical trial (CCT): Single arm trial, prospective, nonrandomized, single‐centre study with an external control group. The design was structured according to the ethical principles of the Declaration of Helsinki and Good Clinical Practice (GCP). The treatment of patients with guided endodontics has been approved by the Ethics Committee of the University Hospitals Leuven, Leuven, Belgium (S64630). Written informed consent was obtained prior to starting the treatment. Additionally, all participants received a verbal explanation in terms suited to their comprehension of the purposes, procedures and potential risks of the study and of their rights as research participants. The Principal Investigator (AT) assured that no deviation from, or changes to the protocol were made except where necessary to eliminate an immediate hazard(s) to the trial participants. The trial was registered in the ISRCTN registry (ISRCTN75277265, https://www.isrctn.com ). 

Between April 2018 and October 2022, all patients referred for endodontic treatment at the Endodontic Department at the University Hospitals of Leuven, Leuven, Belgium were screened for eligibility during the initial consultation. The inclusion criteria were as follows: Tooth presenting with PCO, and Symptoms and/or radiographic signs of apical periodontitis (AP). All patients had a thorough intraoral examination. A periapical radiograph was taken for assessment. If the tooth presented PCO, a score was given based on the visibility of the canal on the periapical radiograph as: (1) root canal not visible (total PCO), (2) root canal visible up to apical root third, (3) root canal visible up to middle root third, (4) root canal visible up to coronal root third. Then, a pre‐operative CBCT scan was taken for further assessment using the NewTom VGi evo (Cefla, Imola, Italy) operating at 110 kVp and 3 mA. If the CBCT volume confirmed the initial diagnosis of PCO, and the clinician evaluated the case as being of high difficulty (AAE, ), patients were candidates for inclusion. The exclusion criteria were: Patients unwilling or unable to comply with the endodontic treatment. Tooth in need of extraction, or with an unfavourable prognosis. 

The sample size was calculated based on the probability of technical failure (perforation or canal not found) when drilling freehanded on teeth presenting PCO. Cvek et al.  reported a probability of technical failure (root canal not found or perforation) of 14.3% (7 out of 49 teeth) when drilling freehanded on anterior teeth with reduced pulpal lumen. Based on this data, a sample size calculation was performed with a power of 80% and a significance level of .05. Considering that the technical failure of guided endodontics was not known, an arbitrary technical failure rate of 2% was set to be clinically relevant. This would imply more than 10% improvement than drilling without guidance. The sample size was calculated by the normal approximation to the comparison of proportions using the TrialSize library from R in an iterative way, in which, for a new calculation, quantiles from an Studentized t‐distribution were used, for which the degrees of freedom corresponded to the requested number of data from the previous calculation. According to the test, a sample size of 59 teeth was needed. This was rounded up to 60 teeth (Figure ). 

Considering that 21 case reports, 11 case series and 1 observational cohort study on 50 patients (Peña‐Bengoa et al., ) show that the use of guides for endodontic treatment offers a highly predictable outcome, with a low risk of iatrogenic damage, randomizing the treatments was not considered to be ethical as it would not guarantee the best quality standards of treatment to the patient (AAE, ). As a result, an external (historical) control group was selected to assess the success rate of guided endodontics treatment. Blinding of the operator was not possible due to the study design. 

A database search was carried out in the clinical management software (KWS, version 3.4.1, IT‐dienst UZ Leuven, Leuven, Belgium), for clinical records from the Endodontic Department at the University Hospitals of Leuven, Leuven, Belgium, on patients that were treated without the use of any guiding system between January 2014 and up October 2022. The following search terms were used to search on all consultation reports from the clinical database of the department of Endodontics: “calcified” OR “calcification” OR “obliterated” OR “obliteration” OR “small” OR “narrow” OR “perforated” OR “perforation” OR “not found” OR “not visible”. After the search was completed, a second operator not related to the clinical treatments (MD) analysed all dental reports and selected the patients for the control group. Patients presenting with all the following inclusion criteria were selected for inclusion: The patient was treated by a specialist in endodontics. A dental microscope was used. A CBCT was available before treatment. The tooth presented PCO visible on a periapical radiograph. The case can be classified as being of high difficulty (AAE, ). Symptoms and/or radiographic signs of AP were present at the time of treatment. 

A pre‐operative CBCT (NewTom VGi evo, Cefla) and an intraoral scan (IOS) (Trios, 3Shape, Copenhagen, Denmark) were taken for every patient selected for guided endodontics treatment. The DICOM images from the CBCT and STL files from the IOS were imported into Mimics Medical software 23.0 (Materialize, Leuven, Belgium). Then the upper or lower jaw, depending on the case, was segmented using the threshold tool, and a 3D model was created. The registration of the IOS to the segmented CBCT model was first performed by using a 3‐point registration method to approximate both structures. Subsequently, the automatic global registration tool was applied and repeated for final registration until no further movement was possible. The correct registration was confirmed visually by checking the contour of the registered IOS on the CBCT images (Figure ). A path for the bur was created maintaining a straight‐line access up to the root canal. Special attention was placed to avoid drilling on the incisal border or buccal side of the tooth when possible. Then, the registered IOS together with the planned trajectory was imported into 3‐matic medical software 14.0 (Materialize) where a tooth‐supported guide was designed (Figure ). After completion of the design, an insertion axis was defined, and the undercut zones were removed by the software's tool. Subsequently, the guide was 3D printed in a biocompatible material (MED 610, Stratasys, Eden Prairie, MN, USA) using the Objet Connex 350 3D printer (Stratasys) and finally, a metallic inner sleeve (REF M.27.28.D100L5, Steco, Steco System‐Technik, Hamburg, Germany) was bonded to the guide (Figure ). 

Guided root canal treatment was performed by the same operator (AT) on all patients, always adhering to the quality guidelines for endodontic treatment from the European Society of Endodontology (ESE, ). First, full rubber dam isolation was placed, with the extension of the isolation field being determined by the extension of the guide. The guide was then placed on the patient's teeth and checked to fit passively on the crowns. The correct fit was checked on both ends of the guide (Figure ). If needed, the interproximal interferences were removed manually from the guide until achieving a passive fit. The stability was checked visually by pressing on one side of the guide (left or right), if there was no movement on the opposite side, the guide was stable and treatment started. Two 1 mm diameter carbide burs with different lengths were available for guided treatment. One short with 21 mm working length and 35 mm total length (REF O.27.28.B044.051, Steco), and a longer one with 28 mm working length and 42 mm total length (REF O.27.28.B044.052, Steco). The decision to use a long or short drill was based upon the case. A new bur was used on every treatment. Before drilling, the entry point was marked with a mechanical pencil through the inner sleeve and enamel was removed by hand with a diamond bur. Then the access cavity was precisely drilled using the selected carbide bur (Steco) mounted on and a Blue W&H WE‐56 LED G handpiece (W&H, Bürmoos, Austria) operated at 20 000 rpm using a pumping movement (Figure ). During drilling, water was irrigated at the entrance of the sleeve using a Stropko Irrigator (Vista Apex, Racine, WI, USA). When the target point was reached, the tooth was examined under the dental microscope. Small size K‐Files (ISO 06 up to 10, Dentsply Sirona, Baillagues, Switzerland) were used initially to negotiate the canal, and after glide path was achieved with a size 15 K‐File (Dentsply Sirona), instrumentation of the canal was performed with Waveone Gold files (Dentsply Sirona) up to at least a medium size (size 35, .06 taper) as final working file. Apical patency was controlled during the whole treatment with a size 10 K‐File (Dentsply Sirona). During treatment, the root canal was rinsed with at least 20 mL of 5% NaOCl in combination with sonic activation using EDDY (VDW, Munich, Germany), then a final irrigation protocol was applied using EDDY and 17% EDTA, and a final rinse with 5% NaOCl. The root was dried using paper points and filled using a vertical compaction technique with warm gutta‐percha and an epoxy sealer (AH Plus sealer, Dentsply Sirona). The access cavity was then filled with composite, occlusion was controlled, and the restoration was polished. A periapical radiograph was taken after treatment and the patient was scheduled for recall after 1 year (Figure ). 

Root canal treatment was performed by a specialist in endodontics not related to the study working at the time at the Endodontic Department at the University Hospitals of Leuven, Leuven, Belgium. Endodontic treatment complied with the quality guidelines for endodontic treatment from the European Society of Endodontology (ESE, ). A dental microscope was used during the whole procedure, and a CBCT was available before treatment for planning and visual guidance during treatment. 

During guided endodontic treatment the primary outcome was evaluated by the operator (AT) as: Canal found Canal not found Perforation As secondary outcome, the qualitative accuracy of the drill path was assessed based on the clinical data and divided into 3 groups (adapted from Buchgreitz et al.  (Figure ): Optimal precision: Drill path centred. Acceptable precision: Drill path peripherally or tangentially transported. A manual correction was needed to find the canal. Technical Failure: Perforation or canal not found. Additionally, the healing after root canal treatment was assessed clinically and radiologically, with periapical radiographs, at 1 year and yearly until periapical healing. A favourable outcome was defined as absence of pain, swelling and other symptoms, no sinus tract, no loss of function and radiological evidence of a normal periodontal ligament space around the root (ESE, ). In the same manner as the guided treatment group, the primary outcome of the endodontic treatment from the control group was classified and recorded as: Canal found Canal not found Perforation 

The following variables were recorded on both treatment groups (guided treatment and control group) for matched pairing: Tooth number. Tooth type: Anterior; incisors and canines, Posterior; premolars and molars. Tooth length in mm (measured on CBCT slices with an axis perpendicular to the tooth). Canal depth in mm: distance in mm from incisal border or occlusal plane to the canal (measured on CBCT slices with an axis perpendicular to the tooth). Canal depth percentage: percentage calculated by dividing the canal depth by the tooth length. Teeth were first matched to a pair from the other group based on the same tooth number and similar canal depths or depth percentages. If no match was found, matching was performed on tooth type (anterior and posterior) and similar canal depths or depth percentages. 

All statistical analysis was done in S+ software, version 8.0 (TIBCO Software, Palo Alto, CA, USA). A technical failure was defined by not finding the canal or having a perforation during treatment. The null hypothesis stated that; H 0 : there is no difference in technical failure between guided endodontics and freehanded treatment. Additionally, the alternative hypothesis stated that; H 1 : Guided endodontics presents less technical failures compared to freehanded treatment. An analysis including all data, without matching, was performed by a generalized linear model for binary data using a logit link function with the primary outcome (canal found or not found/perforation) as response variable and the technique (guided or freehanded) as explanatory variable. p ≤ .05 was considered statistically significant. Data were also matched based on tooth type and canal depth. The primary outcome (canal found or not found/perforation) was analysed by a generalized estimation equations analysis for binomial data. Data were considered to be clustered per pair of control and matched teeth. Only teeth for which a matched pair was found were included in the analysis. p ≤ .05 was considered statistically significant. Additionally, descriptive statistics on the study patient's demographics and healing after root canal treatment were performed. 

A total of 60 teeth in 59 patients (22 males and 37 females) with median age of 48 (range: 14–85) received guided endodontic treatment. Three teeth were excluded from the study; one was because the patient was unable to comply with the treatment, and two teeth were deemed to have unfavourable prognosis and, therefore, extraction was chosen instead of endodontic treatment (Figure ). For the control group, 73 teeth in 69 patients (33 males and 36 females) with median age of 55 (range: 9–85) met the inclusion criteria and were selected for inclusion (Figure ). Descriptive statistics on the demographics of the study patients are shown in Table . After consultation with a professional statistician (WC) and to increase the power of the study, teeth from the guided endodontics group were matched to a similar pair from the control group. First teeth were matched based on the same tooth number and similar canal depths or depth percentages, this matching yield 17 pairs (Table ). However, the statistical model was not stable, and the results were not reliable. To increase the number of pairs and therefore the reliability of the analysis, a second matching was performed based on the same tooth type (anterior and posterior) and similar canal depths or depth percentages. The second attempt yield 37 additional matched pairs. In total, 54 matches were found with an average difference in canal depth of 1.06 mm ± 1.3, and average difference in depth percentage of 6.5% ± 5.4 (Table ). Table shows an overview of non‐matched controls. Outcome of guided endodontics and freehanded control group In the experimental group (guided endodontics), the root canal was found in 59 out of 60 teeth (98.3%). In only 1 case (maxillary canine), the root canal was not found, and the patient was scheduled for endodontic microsurgery. No perforations were recorded. In the control group (freehanded treatment), the root canal was successfully found in 59 out of 73 teeth (81%). In 7 teeth (9.5%), the root canal was not found, and 7 (9.5%) teeth had a perforation. An analysis of all data, without matching, for the assessment of the outcome of guided endodontics in comparison with freehand treatment, showed that guided endodontics presented statistically significant better outcome than freehand treatment ( p < .05; Table ). The same result was obtained when assessing only matched pairs of teeth ( n = 54) and excluding the unmatched data ( p < .05; Table ). The null hypothesis (H 0 ) stating that there is no difference in technical failures between guided endodontics and freehanded treatment was therefore rejected. Moreover, from all 60 teeth treated with guided endodontics, 49 presented an optimal precision with a centred drill path. On 10 teeth (8 maxillary incisors and 2 lower premolars) an acceptable precision was obtained, and a correction was needed to find the canal. One technical failure was registered where the root canal was not found. Follow‐up and drop‐outs Eight patients failed to attend the recall appointment and did not want to reschedule (13% drop out). A total of 44 teeth healed (73%); 34 after the first year, 8 after 2 years and 3 after 3 years of recall. Four teeth showed signs of ongoing healing on the periapical radiograph (7%), and 4 teeth (7%) did not show any signs of healing after recall; 2 of them were scheduled for endodontic microsurgery and healed 1 year after surgery, the other two patients denied surgery. 

In the experimental group (guided endodontics), the root canal was found in 59 out of 60 teeth (98.3%). In only 1 case (maxillary canine), the root canal was not found, and the patient was scheduled for endodontic microsurgery. No perforations were recorded. In the control group (freehanded treatment), the root canal was successfully found in 59 out of 73 teeth (81%). In 7 teeth (9.5%), the root canal was not found, and 7 (9.5%) teeth had a perforation. An analysis of all data, without matching, for the assessment of the outcome of guided endodontics in comparison with freehand treatment, showed that guided endodontics presented statistically significant better outcome than freehand treatment ( p < .05; Table ). The same result was obtained when assessing only matched pairs of teeth ( n = 54) and excluding the unmatched data ( p < .05; Table ). The null hypothesis (H 0 ) stating that there is no difference in technical failures between guided endodontics and freehanded treatment was therefore rejected. Moreover, from all 60 teeth treated with guided endodontics, 49 presented an optimal precision with a centred drill path. On 10 teeth (8 maxillary incisors and 2 lower premolars) an acceptable precision was obtained, and a correction was needed to find the canal. One technical failure was registered where the root canal was not found. 

Eight patients failed to attend the recall appointment and did not want to reschedule (13% drop out). A total of 44 teeth healed (73%); 34 after the first year, 8 after 2 years and 3 after 3 years of recall. Four teeth showed signs of ongoing healing on the periapical radiograph (7%), and 4 teeth (7%) did not show any signs of healing after recall; 2 of them were scheduled for endodontic microsurgery and healed 1 year after surgery, the other two patients denied surgery. 

After assessment of all data, and further matched pair analysis, guided endodontics presented a statistically significant better outcome than freehanded treatment ( p ≤ .05; Table ). The null hypothesis was therefore rejected, and data favour the alternative hypothesis stating that guided endodontics presents less technical failures compared to freehanded treatment. All patients were appointed for recall 1 year after root canal treatment and continued to follow up yearly until periapical healing. A total of 13% dropped out from the follow‐up and could not be controlled for healing. Without considering the dropouts, a 92% success rate of the endodontic treatment was observed. This includes all healed cases ( n = 44) and teeth that showed signs of ongoing healing ( n = 4) with absence of symptoms. Several case reports and case series have shown the potential of guided endodontics as treatment option in teeth presenting PCO (Peña‐Bengoa et al., ). However, high‐quality prospective clinical studies are lacking (Connert et al., ; Peña‐Bengoa et al., ). While randomized control trials are the gold standard, randomizing the treatments in the present study was not considered to be ethical as the current evidence shows that the use of guides for endodontic treatment offers a highly predictable outcome, with a low risk of iatrogenic damage (Peña‐Bengoa et al., ). Non‐randomized control trials, on the other hand, allow the comparison between a group receiving an intervention with an historical/external control group. A qualitative assessment of the accuracy of the drill path, adapted from Buchgreitz et al. , was performed based on clinical data recorded during treatment. If the canal was located without correcting the trajectory of the access cavity after the use of the guide, an optimal precision was registered. If a manual correction was needed, an acceptable precision was registered. In their study, they found that, in a total of 50 patients, 22 presented an optimal precision and 28 an acceptable precision. However, the authors classified the teeth based exclusively on the appearance of the drill path on the final periapical radiograph and divided them in two groups: drill path centred (optimal precision), and drill path peripherally or tangentially transported (acceptable precision). Such method may underestimate tangential deviations on the bucco‐lingual direction due to the two‐dimensional nature of the periapical radiograph. Nevertheless, from the 50 patients treated, no manual corrections to the direction of the drill path were mentioned, which correlates with the results from the present study ( n = 49 optimal precision). There were cases when after initial drilling to the planned depth, there was no trace of the canal visible under the dental microscope. When this was the case, an intra‐operative periapical radiograph was taken for evaluation. Then, the operator could decide to drill deeper with the use of the guide or, in the case where a tangential deviation was visible on the radiograph, to manually correct the path with a long neck bur or ultrasonic tip in the search for the permeable portion of the root canal ( n = 10 acceptable precision). All these corrections were small, as shown by data on the clinical accuracy of guided endodontics previously measured and reported by the authors (Torres et al., , ) Results show an average apical deviation of 0.45 mm (min 0 mm – max 1.2 mm). In either case, guided endodontics led to a predictable and efficient location of the obliterated canal, allowing for a conservative access, deep inside the root, with minimal substance loss as stated previously (Connert et al., ). Buchgreitz et al.  found that in mandibular front teeth, where the length of pulp space obliteration was shorter than in maxillary teeth, optimal precision was most frequently achieved. However, in the present study, no difference was found between canal depths measured on CBCT from maxillary incisors (mean 12 mm) in comparison with mandibular incisors (mean 11.4 mm). Manual correction was more frequently needed in maxillary incisors (acceptable precision), and this may be explained due to the higher overall prevalence of maxillary incisors treated in the present study (65% vs. 18%, Table ). Nevertheless, deviations from the planned drilled path could be explained due to small errors during acquisition of the intraoral model, 3D printing of the guide or inadequate fit of the guide in the mouth (Fonseca Tavares et al., ). Additionally, the bur should be correctly positioned and introduced within the sleeve, with no resistance experienced when introducing the bur inside of the sleeve. This can be controlled by performing a pumping motion with the bur inside of the sleeve before drilling. No perforations were recorded in the guided group in comparison with 7 perforations (9.6%) recorded in the control group. This is of utmost importance, as several long‐term studies on the outcome of nonsurgical root canal treatment have shown that the presence of root perforation can negatively impact the success rate of root canal treatment (de Chevigny et al., ; Kvinnsland et al., ; Ng et al., ; Van Nieuwenhuysen et al., ). The message for clinicians is clearly that caution must be an important aspect during treatment, as such complications can lead to tooth extraction (Kvinnsland et al., ; Ng et al., ; Van Nieuwenhuysen et al., ). However, although no perforations were recorded in the guided group, in 1 case the root canal was not found. The canal was visualized on the CBCT at a depth of 20 mm on a 23 mm long maxillary canine. Upon drilling with the aid of a 3D‐printed guide, no trace of the root canal could be visualized under the dental microscope. A control periapical radiograph revealed the deviation of the drill path from the original trajectory. Due to the cavity depth and high difficulty of the case, decision was taken to acquire an intra‐operative limited field of view CBCT scan to visualize the position of the access cavity inside of the root on three‐dimensions. Upon assessment of the CBCT, the operator decided to stop the treatment as further drilling could lead to the perforation of the root. The patient was then scheduled for endodontic microsurgery and followed up until healing (Figure ). A similar approach was also reported for management of an unsuccessful case with technical failure (perforation) after guided endodontics (Fonseca Tavares et al., ). The authors stated that endodontic microsurgery should be considered the treatment of choice when guided endodontics cannot be used safely or fails. On the other hand, endodontic microsurgery might be considered as the initial treatment option on teeth presenting with apical periodontitis and PCO. On a prospective study (Jonasson et al., ), a total of 57 patients, presenting with limited orthograde access to the root canal, were endodontically treated from the root apex through endodontic microsurgery. After initial removal of the root apex, the canals were instrumented with files, irrigated with 0.5% sodium hypochlorite and filled with an epoxy base sealer and thermo‐plasticized gutta‐percha. Retrograde root canal treatment was successful in 90% of cases after 2‐year follow‐up. This could be an alternative treatment option in cases presenting PCO, where accessing the canal apically could result in a less invasive approach, from a tooth perspective, considering the amount of coronal dentin that needs to be removed to reach the root canal and the possibility of a technical failure during orthograde treatment. Moreover, the use of modern filling materials, such as MTA, might improve the success rate due to its alleged favourable tissue response and sealing properties over time. One of the limitations of the current clinical trial is that there was no randomization of the patients. Instead, a control group was selected from the database from the same centre. To account for nonrandomization and perform a strong analysis, a matched pair analysis was performed. All root canal treatments from the control group were performed by a specialist in endodontics with the aid of a dental microscope and a CBCT prior to treatment. Although there was no control on how the treatments were performed, and the outcome of the treatment can depend on the operator's experience, a specialist in endodontics can have the highest scores when detecting canals with simulated PCO, compared to a general dentist and a dental student (Connert et al., ). At the same time, to improve the quality of the evidence and remove additional variables, all guided endodontic treatments were performed by a single operator. Moreover, it has been shown in the literature that this technique is not dependent on the operator's experience (Connert et al., ; Torres et al., , ; Zehnder et al., ). The results from the current clinical trial are in line with similar studies (Moreno‐Rabie et al., ; Peña‐Bengoa et al., ). Many of the known benefits of guided endodontics were observed during treatment of the patients. Such benefits are: a reduce probability of iatrogenic damage together with a high accuracy (likelihood of finding the canal), a conservative access cavity up to the canal can be created allowing for a minimally invasive treatment while maintaining as much of the root's rigidity as possible (Lang et al., ), reduction of chair time, and it allows the pre‐operative visualization of the case and detailed planification without having to mentally transfer the planning to the clinical situation (van der Meer et al., ). These advantages are hard to overlook when deciding the best treatment option for an otherwise highly complex case, where the risk of technical failure would be high by treating on a conventional manner and could precipitate the extraction of the tooth (Cvek et al., ; de Chevigny et al., ; Kvinnsland et al., ; Ng et al., ; Van Nieuwenhuysen et al., ). However, although the use of a 3D‐printed guide can facilitate treatment, it is still a complex procedure which should be carried out by an experienced Endodontist with the aid of a dental microscope. It still presents limitations, as it has been shown here previously by a failed case of an upper canine and in a recently published case report (Fonseca Tavares et al., ). In contrast to static guidance, other techniques such as the use of dynamic navigation can also be of benefit for the treatment of PCO in the future (Connert et al., ; Leontiev et al., ; Torres et al., ). However, this technique requires a high acquisition cost for the device and extensive training is needed prior to its clinical use (Torres et al., ). Another alternative can be the use of augmented reality. Yet, despite showing promising results for potential clinical use, it needs further development and research (Farronato et al., ). 

Guided endodontics showed a statistically significant better outcome than freehanded treatment. It resulted in less technical failures compared to conventional treatment. However, it is a complex procedure which should be carried out by an experienced endodontist with the aid of a dental microscope. 

A. Torres: Conceptualization, methodology, investigation, resources, data curation, writing original draft, writing review and editing, visualization, project administration. M. Dierickx, K. Lerut, S Bleyen: methodology, data curation, review, and editing. E. Shaheen: methodology, resources. W. Coucke: formal statistical analysis. MS. Pedano, P. Lambrechts: Writing review and editing, supervision. R. Jacobs: Writing review and editing, supervision, project administration. 

This research did not receive any funding. 

The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria, educational grants, participation in speakers' bureaus, membership, employment, consultancies, stock ownership, or other equity interest and expert testimony or patent‐licensing arrangements) or non‐financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. 

