All patients will voluntarily seek endodontic treatment in the Brazilian Unified Health System in the cities of Itabuna, in the State of Bahia, in Goiânia, in the State of Goiás, Brazil. After an assessment of eligibility and informed consent, patients will be randomly assigned to one of 3 clinical study groups. Patients who agree to participate in this study will sign an informed consent form. Sample Size: The determination of the sample size will be performed sequentially, with a minimum of 210 statistical units (teeth) to be recruited in the first stage, and the second stage of recruitment will be performed if the selection is insufficient to clinically and radiographically identify valid cases. This sampling will also allow the adjustment of the sample size for the intra-subject correlation of statistical units (teeth). In the first stage, 150 adults aged 18 to 60 years, with at least one tooth diagnosed with asymptomatic apical periodontitis and periradicular lesion with a diameter between 1 and 5 mm, will be recruited. Allocation and blinding: Only examiners can open the envelope to check the group allocation and perform the interventions according to the instructions of this study. As a double-blinded trial, the patients and outcome evaluators will be blinded to the group assignment until the completion of the study. Interventions: In order to treat apical periodontitis, in the first visit, the same endodontic instrumentation protocol will be performed for all teeth randomly divided into the 3 study groups. What will vary will be complementary and additional maneuvers such as the use of ultrasonic activation and intracanal medication between visits of endodontic instrumentation. All endodontic therapy procedures will be performed under a dental microscope, except for anesthesia and rubber dam placement steps.

The study will be conducted in the private offices of two of the co-investigators involved in the study (GMA and VHMC), located in the cities of Itabuna (Bahia) and Goiânia (Goiás), Brazil, respectively. All investigators and examiners are specialists in Endodontics with more than 10 years of clinical experience. They will participate in this randomized clinical trial after receiving adequate training to obtain a comprehensive view of the principles and strategy of the 3 clinical approaches that will be used.

Description: First clinical appointment: The first visit will include the following clinical protocol depending on the study group. For the 3 groups (Group 1, Group 2 and Group 3): (1) Anesthesia and caries removal: After local anesthesia with articaine hydrochloride and epinephrine injection (with 1:200,000 adrenaline), all decayed tissue from the tooth is removed; (2) Isolation and access preparation. The tooth is isolated with a rubber dam, disinfected and the pulp chamber will be completely unroofed; (3) Initial irrigation with 5 ml of 5.25% NaOCl; (4) Root canal preparation: The #10 C-Pilot file will be used to perform the glide path along the length of the tooth on the radiograph, irrigated with 2 ml of 5.25% NaOCl, followed by rotary instrumentation with #15/.03, #25/.04 and #30/.05 NiTi files, initially in the cervical and middle thirds, after which the working length with foraminal locator will be performed. Finally, the instrumentation of the apical third will be performed with the same sequence of NiTi rotary files used previously; (5) The canal will be copiously irrigated in three stages using 10ml of 5.25% NaOCl for each of thirds: cervical, middle and apical, totaling 30ml, followed by a final rinse with 10ml of 5.25% NaOCl stirred with the ultrasonic inserts and 10 ml of 17% EDTA stirred also with ultrasonic inserts. The final rinse will be carried out with 10ml of saline solution. Intracanal dressing: Group 1 will not receive intracanal dressing because it will be concluded in single visit. Group 2 will receive intracanal dressing with Ca(OH)2/CPMC/glycerin paste for a period of 7 days. To restrict bacterial regrowth and supply continued disinfection, the root canal will be filled homogeneously to the working length with Ca(OH)2/CPMC/glycerin paste. The tooth will be shielded with glass ionomer cement (GIC) as a temporary restoration. Group 3 will be without intracanal dressing for a period of 2 days, taking into account that the tooth will be shielded with GIC as a temporary restoration. Obturation: Only for Group 1, the root canals will be filled in the first visit. In this group, a #30/.05 gutta-percha cone and epoxy resin-based sealer with the continuous heat wave technique and a final restoration with composite resin will be used. Second clinical appointment: The second visit will include the following clinical protocol depending on the study group. For the 2 remaining groups (Group 2 and Group 3): (1) Anesthesia and restorative material removal. After local anesthesia with articaine hydrochloride and epinephrine injection (with 1:200,000 adrenaline, all temporary restorative material from the tooth is removed. (2) Isolation and Access. The tooth is isolated with a rubber dam and the root canal will be accessed one more time. Group 2: (1) After 7 days, the intracanal dressing will be removed and the root canal will receive a new chemo-mechanical preparation, identical to the one performed in the first visit, and then it will be filled and permanently restored similarly to Group 1. Group 3: (1) After 2 days, the root canal will receive a new chemo-mechanical preparation, identical to the one performed in the first visit, and then it will be filled and permanently restored similarly to Group 1.