This randomized controlled parallel clinical trial was designed to compare the post-endodontic pain and treatment outcome between minimally invasive and conventional RCT. The study was approved by the Institutional Review Board of Yonsei University Dental Hospital (no. 2-2020-0003) and registered at the Clinical Research Information Service (CRIS, no. KCT0005351: 25/08/2020). We enrolled systematically healthy patients aged 18–82 years between April 2020 and March 2021. All patients were given written informed consent papers that explained the study and required them to sign to participate.
Patient selection
The inclusion criteria were as follows: healthy individuals (age ≥ 18) and mature permanent teeth that need RCT, either with vital or necrotic pulp. The exclusion criteria were as follows: previously initiated or treated teeth, teeth associated with periodontal pocket extending beyond the apical third of root, patients who took analgesics within 24 h before the treatment, patients who were disabled for proper communication, and teeth with canals that cannot negotiate within 2 mm of the radiographic apex.
Sample-size determination and randomization
This clinical trial was designed to evaluate two key outcomes: short-term postoperative pain, the results of which are reported in this study, and long-term success rates of the respective treatment procedures, to be compared later. Both outcomes were considered when calculating the sample size, with the larger of the two results being selected as the definitive sample size. The required sample size for comparing postoperative pain between the two groups was calculated using G*Power 3.1 software (Franz Faul, University of Kiel, Germany) with a significance level of 5%, a statistical power of 80%, and an effect size of 0.5. The sample size calculation for comparing success rates was based on the outcome of a previous clinical trial on nonsurgical RCT (16). According to Kim et al. (17), the success rates for the continuous wave of condensation technique with a resin-based sealer and the sealer-based obturation technique with a calcium silicate sealer were reported as 92.3% and 94.3%, respectively, using loose criteria. This study was designed as an equivalence trial, with an equivalence limit of 10%, a significance level of 5%, and a power of 90%. Based on these parameters, the required number of cases in each group was determined to be 75. Considering a dropout rate of 20%, the final estimated sample size was 180 cases.
The study employed a rigorous process to maintain impartiality. An unbiased assistant, unaware of the study's objectives, generated a set of random numbers using the Sealed Envelope website (https://www.sealedenvelope.com/) with a 1:1 allocation ratio and employing random block sizes of 6. To ensure absolute secrecy, the resulting list was securely stored in a locked file cabinet and remained confidential. It was only unveiled by the impartial assistant after participant inclusion in the study but before the intervention phase. Each participant received an enrollment number based on the random list, determining their assignment to either the CP or MP treatment group in accordance with the established protocol.
Preoperative clinical and radiographic evaluation
Before beginning treatment, each tooth was examined both clinically and radiographically. Percussion tests and periodontal probing were carried out, and the presence of sinus tracts was also recorded. The pulp sensibility testing including cold and electric pulp tests confirmed the need for RCT. Detecting bleeding in the pulp chamber was essential for diagnosing a vital pulp. If no vital tissue was present within the pulp chamber, it was considered necrotic. The periapical index (PAI) score was recorded (18) and dichotomized into healthy (PAI scores of 1–2) and unhealthy (PAI scores of 3–5) periapical statuses.
Treatment protocol
Treatments were performed at a single center by 10 operators: 3 professors and 7 well-trained residents in the Department of Conservative Dentistry under dental operating microscopes (OPMI pico; Carl Zeiss, Göttingen, Germany). All treatments were performed under rubber dam isolation, and finished in two or more visits. The concentration of sodium hypochlorite (NaOCl) used in the treatment was 2.5% and that of ethylenediamine tetraacetic acid (EDTA) was 18%.
In the CP group, on the first visit, an access cavity was formed using high-speed burs under local anesthesia (infiltration and/or block anesthesia). Canal length was measured using electronic apex locators (DentaPort Root zx II, Morita, Irvine, USA), and then a periapical radiograph was taken with initial apical file insertion. Pulp extirpation and canal shaping were simultaneously performed using a rotary Ni-Ti file system (ProTaper Gold, Dentsply Sirona, Ballaigues, Switzerland). During the canal shaping process, canal irrigation with NaOCl was performed using a 30-gauge notched-tip needle (Sungshim Medical Co., Bucheon-si, Korea). The root canal preparation was completed using a PTG F2 instrument in curved canals and a PTG F3 instrument in straight canals. After canal shaping, the canals were soaked with NaOCl for 5 min.
During the obturation visit, each canal was re-instrumented with the previous final instrument and irrigated with 1 mL of EDTA, followed by 3 mL of NaOCl. Appropriately sized gutta-percha cones were adapted to the root canals and checked with a periapical radiograph. Then, canals were soaked with NaOCl for 15 s, and the irrigant was replaced. To ensure an equal final irrigation time in both groups, the process was repeated three times. Canals were dried with paper points, and CWC was performed. Gutta-percha cones were coated using AH Plus sealer (Dentsply Sirona) and inserted into the prepared root canals. A heated plugger (SuperEndo Alpha 2, B & L Biotech, Ansan, Korea) that could penetrate 4 or 5 mm short of the working length was inserted into the canal to cut and compact the master cone. Backfilling of the canal was performed using a thermoplastic injection technique using SuperEndo Beta 2 (B & L Biotech).
In the MP group, access opening, canal length measurement, and radiography were performed using the same protocol as the CP group. For canal shaping, a TN prime shaping file was used in curved canals, and a medium file was used in straight canals. At the end of the treatment, the irrigant was activated by applying ultrasonic vibration for 15 s (Endosonic Blue, Maruchi, Wonju, Korea). After drying the canals, premixed syringe-type CH (Cleanical, Maruchi) was placed into the canal. Subsequently, the paste was evenly placed to the canal wall using a gutta-percha that was slightly smaller than the shaped root canal.
On the obturation visit, CH was removed using the previous final instrument, and irrigation using 1 mL of EDTA and 3 mL of NaOCl was performed. The gutta-percha master cone fit was verified with a periapical radiograph. Passive UI was performed with NaOCl for 15 s in each canal, and this procedure was repeated three times consecutively. After canal drying, SBO was used for the obturation. Calcium silicate-based sealer (Endoseal TCS, Maruchi, Wonju, Korea) was dispensed into the middle third of the canal using a 24-gauge needle tip, and a matching-taper single gutta-percha cone (DiaDent, Cheongjusi, Korea) was inserted into the canal up to the working length. A heated plugger was used to sear the gutta-percha point at the orifice level. Obtura S-Kondenser (Obtura Spartan, Earth City, MO) was used to vertically compact the gutta-percha.
At the end of the first visit for both groups, an analgesic (ibuprofen 200 mg tablets) was prescribed, and patients were instructed to intake them in case of significant pain.
Preoperative and Postoperative pain assessment
Before the administration of local anesthesia at the first visit, patients were asked to record the preoperative pain using a 0–10 numerical rating scale (NRS). Along with the numeric ratings, a modified Wong-Baker FACES scale was presented to the patients to help them in scoring the pain: no pain (0), mild pain (1–2), moderate to severe pain (3–6), very severe pain (7–9), and worst pain possible (10). After the treatment on the first visit, each patient received a pain diary to write down their pain level using the same scale at the following time points: 4 h, 1, 2, 3, 4, 5, 6, and 7 days after instrumentation. Patients were also requested to record the date and time of their analgesic intake in the diary. For the assessment of pain after canal obturation, each patient received a phone call and was asked to report their pain score 1 day after treatment.
Statistical analysis
Statistical analyses were conducted using R version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria) and Statistical Package for the Social Sciences software version 26 (IBM Corp., Armonk, NY). The level of significance was set at .05.
T-tests, chi-squared tests, or Fischer’s exact tests were used to evaluate the data related to the baseline characteristics of the included study participants and the analgesic intake ratio. Repeated measures analysis of variance (RM-ANOVA) followed by Tukey’s post-hoc test was performed to compare NRS scores among all time-points for each treatment group. Mann–Whitney U-test was used to compare postoperative pain at each time interval between the two groups.
The highest score among the NRS recorded at 8 post-instrumentation time points for each patient was selected and then dichotomized into absent/mild (responses lower than 3) and moderate/intense (responses 3 or higher). The post-obturation pain score was dichotomized in the same way as mentioned above. All variables were analyzed using multivariate logistic regression analysis, followed by a stepwise method to investigate the factors associated with moderate /intense pain after instrumentation and obturation.