Ethical standards
The trial was reviewed and approved by the Researcch Ethics Committee, Faculty of Dentistry, Cairo University (reference no. 40922). The study started in December 2021 and was completed in October 2023 after registration at ClinicalTrials.gov “reference no. NCT05168553 (23/12/2021)”. A signed informed consent was obtained from each parent/caregiver before starting the trial. An informed consent was obtained from each patient aged 16 years or older. All procedures in studies involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Sampling
Since no previous trial had addressed the diminishing in periapical radiolucency of retreated mature permanent teeth with REPs compared to NS-RCR, a pilot study that included 20 teeth (10 teeth per group) was conducted. Hedges’s g-a corrected effect size-was calculated for the difference between the two group means was calculated22 where the means and standard deviations (SD) of the periapical index (PAI) scores of intervention and control groups were 3.44mm ± 0.65 and 3.87mm ± 0.95 respectively. The estimated unbiased effect size (Hedges’s gs) was 0.658. Analyses were performed at an alpha level of significance of 0.05 and a study power of 0.80. A total of 66 teeth was calculated using G*Power 3.1.9.4 software after adding 10% to consider the possible drop-off.
Randomization, allocation and blinding
Teeth were distributed at random using a permuted block randomization technique with a block size of four. An independent investigator organised the randomization procedures using computer-generated software. A total of 66 identical, properly sealed, opaque envelopes were created before the clinical procedures began. Envelopes contained identical double-folded paper sheets wrapped within alumnium foil. According to the printed code on the paper sheet indicating the retreatment technique, each envelope was placed in one of the two identical containers. Two envelopes were chosen from each pile and shuffled by an impartial nurse who was unaware of the trial’s purpose, nature, allocation, and treatment codes. The patient’s legal guardian randomly picked one envelope23. The participants were divided into two parallel arms, one was treated with REPs using the triggered BC approach (intervention), and the other (control) was treated with NS-RCR.
Eligibility standards
Inclusion standards
Under-18-year-old healthy adolescents with mature permanent single-rooted previously traumatized incisors with chronic apical abscess or asymptomatic apical periodontitis that ere indicated for retreatment.
Only teeth with a periapical index (PAI) score ≥ 3.
Exclusion standards
Teeth with previous attempts for endodontic retreatment were excluded.
Teeth with periodontal problems, non-restorable crowns, teeth that needed post-placement, and non-restorable crowns.
Teeth with previous endodontic treatment and a history of severe luxative injuries
Tooth candidates for endodontic surgery including (1) getting a biopsy, (2) removing intracanal broken files, (3) persistent periapical lesions standing for a long time, (4) radicular perforation, (5) root fracture, (6) obstructed root canals, (7) being unable to remove all of the old gutta-percha, or (8) having material protrude beyond the apex with persistent apical lesions for a long duration.
Clinical procedures
Intervention group
A two-appointment approach was considered for both groups. At the first visit, the tooth was anesthesized with one cartridge (1.7 mL) of articaine hydrochloride 4% and epinephrine 1:100,000 (Septocaine®, SEPTODONT Ltd. Paris, France). A rubber dam clamp was placed after confirming the lip numbness. The old restoration was removed from a previously accessed cavity. The heat and Hedstrom file was used to remove the gutta-percha. The gutta-percha was softened using a hot plugger, and then a suitable-sized H-file (MANI Inc., Tochigi, Japan) was screwed into and pulled out of the gutta-percha. No chemical solvents were used, and a periapical radiograph was used to make sure there were no gutta-percha residues24. The working length was determined, using an electronic apex locator (DentaPort ZX, J. Morita Corp., Kyoto, Japan). Using a 30-gauge side-vented needle (Endo-Top®; PPH CERKAMED, Kwiatkowskiego, Poland), the root canal was cleaned with a 1.5% NaOCl irrigation solution for 20 mL over 5 min. The irrigation needle was adjusted to its working length at 1 mm from the root apex. The root canal was then filled for 5 min with 20 mL of 17% ethylenediaminetetraacetic acid (Prevest, DenPro. Jammu, India). Alternate irrigation with NaOCl and EDTA facilitated the debonding of the remaining filling material. Finally, 20 mL of 0.9% saline solution was used to cleanse the root canal. After the root canal had dried out, calcium hydroxide (CH) (UltraCal, Ultradent, Utah, USA) was inserted as an intracanal medication. (Equia Fil™, GC Corp., Tokyo, Japan) a glass ionomer was used to close the access6.
After two weeks, the second appointment was scheduled. The tooth was isolated with a rubber dam after a 3% mepivacaine plain local anaesthetic injection (Scandonest®, Septodont, Saint-Maur-des-Fosses, France) was applied. Coronal restoration and CH intracanal dressing were removed using 5 mL of 0.9% saline. Final irrigation with 5 mL of 0.9% saline and 20 mL of 17% EDTA that was passively activated with an ultrasonic noncutting tool for one minute was carried out. Suitable-sized paper points were introduced to dry the root canals.
To trigger intracanal BC formation, a sterile K-file size #35 (MANI Inc., Tochigi, Japan) was passed 2 mm beyond the apical foramen. Bleeding was extended to the cementoenamel junction (CEJ). The cotton pellet was left for 5 min until clotting occurred. As instructed by the manufacturer, Biodentine (Biodentine®, Septodont, Saint-Maur-des-Fossés, France) was packed against a collagen resorpable matrix (Collacone®, Botiss Biomaterials, Berlin, Germany) that was placed over the created BC19. Before restoring the coronal portion, a radiograph was taken for qualitative assessment. A base of light-cured resin-modified glass ionomer restorative material (Riva light cure, SDI, Bayswater, Australia) and composite resin was used to seal the access (Tetric N Ceram Bulk Fill, Ivoclar, Vivadent AG, Schaan, Liechtenstein).
Control group
Similar to the intervention group, the old gutta-percha was removed. To evaluate the working length, a suitable-sized initial file engaged in the root canal was inserted with the use of a periapical radiograph and electronic apex locator (DentaPort ZX Apex Locator, J. Morita Corp., Kyoto, Japan). A minimum of 3 successive manual K-files (MANI Inc., Tochigi, Japan) were used for mechanical instrumentation. The access cavity temporization procedure, dryness protocol, and CH intracanal administration were also followed. Patients were recalled two weeks later. After confirming that signs and symptoms were relieved, root canals were filled with gutta-percha (Dia-Pro W™, Diadent®, Chungcheongbuk-do, Korea) and resin-based root canal sealer (ADSEAL, Meta Biomed Co., Chungcheongbuk-do, Korea). The access cavity was sealed, just like the REPs group.
Postoperative radiographs were taken in both groups to evaluate the obturation’s quality and provide a baseline for future comparison. In the control group, teeth with overextended fillings were excluded from the analysis.
Outcomes assessment
Radiographic reduction of the periapical radiolucency
Radiographic assessments were performed at baseline (T0), after 6 months (T1) and after 12 months (T2). A long cone “paralleling technique” with a receptor holder was used to assess the changes in periapical radiolucency uniformly after mounting a size 2 periapical film (SKYDENT E, Skýcov, Slovakia) to a silicone biting stick6,25.
The PAI classification system was used to monitor the dimensional changes in the periapical radiolucency26. The PAI method includes 5 scores: “1” indicates normal periapical structure, “2” and “3” indicate minor alterations in bone structure and some mineral loss, respectively, and “4” and “5” indicate severe periodontitis with aggravating characteristics. Scores of “1” and “2” indicated healthy periodontal structures, whereas scores of “3”, “4” and “5” denoted sick periodontal structures.
Clinical success and pulp sensibility test
After 6 months (T1) and after 12 months (T2), if any of the following characteristics were observed during an examination: (i) pain on percussion, (ii) sinus tract oedema, (iii) abnormal tooth movement, or both—clinical failure would result. At T1 and T2, the electric pulp tester (EPT) (Pulp Tester DY 310, Denjoy Dental Co.) was used to assess the pulp sensations in the intervention group. The tooth was dried and isolated, then a small amount of fluoridated tooth was applied. The patient’s lip was attached to the metal clip. For comparison, baseline reading was established through testing the reading of the adjacent tooth.The average of the three EPT measurements taken at 5-min intervals was calculated.
Standardization and calibration
A single expert in pediatric dentistry with seven years of experience in RES performed all clinical procedures. For calibration, 20 reference x-rays were independently assessed by each examiner. At the baseline (T0) and follow-up intervals (T1 and T2), the radiographic examination was carried out independently by two endodontic professionals. The inter-examiner reliability and the intra-examiner reliability were tested using Cohen’s Kappa statistics (κ) and intra-class correlation coefficient (ICC). The assessors were blinded to the allocation group during the clinical evaluation. While masking the nature of treatment was impossible during the radiographic assessment.
Statistical analysis
Data were analysed using IBM SPSS® Statistics version 21. Data were checked for the normality of the distribution of PAI scores using the Kolmogorov–Smirnov, and Shapiro–Wilk tests. To compare the PAI median values between both groups, the Mann–Whitney test was used. Within each group, the change of PAI medians over the follow-up intervals was tested using Wilcoxon signed rank tests (T0 versus T1, T0 versus T2 and T1 versus T2). Using the repeated measure analysis of variance, the normally distributed EPT values at the T1 and T2 follow-up points in the REPs group were examined (ANOVA). The alpha level of significance was set at 0.05 at 95% CI.
Research involving human participants and/or animals
All procedures in studies involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent
Clinical procedures were launched after obtaining written informed consent from each participant’s legal guardian. An informed consents were obtained from each patient of 16 years or above.
