Chronic Apical PeriodontitisNCT07353008
Effect of Different Chelation Protocols on the Healing of Periapical Lesions in Teeth With Chronic Apical Periodontitis
A study testing Final irrigation with 2.5% NaOCl and 17% EDTA, Final irrigation with 2.5% NaOCl and 9% HEBP and Irrigation with 2.5% NaOCl-9% HEBP during both preparation and final irrigation in people with Chronic Apical Periodontitis, run by Mustafa Kemal University at 1 site in Turkey (Türkiye).
Trial summary
The aim of this study is to evaluate the effects of different irrigation protocols using ethylenediaminetetraacetic acid (EDTA) and etidronic acid (HEBP) on periapical lesion healing and postoperative pain in single-rooted, single-canal mandibular anterior and premolar teeth diagnosed with chronic apical periodontitis. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Apical Periodontitis
- What is being tested?
- Final irrigation with 2.5% NaOCl and 17% EDTA, Final irrigation with 2.5% NaOCl and 9% HEBP and Irrigation with 2.5% NaOCl-9% HEBP during both preparation and final irrigation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Dec 2025to Aug 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy patients of both sexes aged 18-60 years, with no systemic diseases, will be screened for inclusion in the study. Strict eligibility criteria will be applied.
- Eligible patients will present with restorable mandibular single-rooted premolar and anterior teeth, a healthy periodontal status (periodontal pocket depth ≤3 mm), and a clinical diagnosis of chronic apical periodontitis. The diagnosis of chronic apical periodontitis will be based on the absence of clinical symptoms, the presence of pulpal necrosis, negative responses to electric pulp testing and cold testing, and the detection of a radiolucent area in the periapical region on radiographic examination. In addition, included teeth must exhibit a periapical lesion with a Periapical Index (PAI) score of 2 or higher.
Who cannot join
- Patients with systemic diseases (such as diabetes mellitus, hypertension, chronic liver disease, or coagulation disorders), those with bone metabolism disorders and/or those using medications that affect bone metabolism (including steroids and bisphosphonates), and pregnant patients will be excluded from the study.
- In addition, teeth presenting with periodontal pocket depths greater than 3 mm, internal or external root resorption, vertical or horizontal root fractures, a history of previous root canal treatment, the presence of a sinus tract, or intraoral or extraoral abscess associated with the involved tooth, as well as teeth deemed non-restorable, will not be included in the study.
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Department of Endodontics, Faculty of Dentistry, Hatay Mustafa Kemal University
Hatay, 31000
About this study
The aim of this study is to evaluate the effects of different irrigation protocols using ethylenediaminetetraacetic acid (EDTA) and etidronic acid (HEBP) on periapical lesion healing and postoperative pain in single-rooted, single-canal mandibular anterior and premolar teeth diagnosed with chronic apical periodontitis.
Read the detailed description
Materials and Methods Study Design This study was designed as a randomized clinical trial with three parallel experimental arms and included data obtained from a total of 63 patients.
Randomization and Blinding
Patients were randomly allocated to one of the following three groups:
Irrigation with 2.5% sodium hypochlorite (NaOCl) during canal preparation and 17% ethylenediaminetetraacetic acid (EDTA) as the final irrigant; Irrigation with 2.5% NaOCl during canal preparation and a combination of 2.5% NaOCl and 9% etidronic acid (HEBP) as the final irrigant; Irrigation with a mixture of 2.5% NaOCl and 9% HEBP throughout the entire irrigation protocol.
Randomization was performed using an online randomization tool (www.randomizer.org). Block randomization with a block size of four was applied to ensure an equal 1:1 allocation among the study groups. All endodontic procedures were performed by a single experienced operator. Due to the inherent differences between the irrigation protocols, blinding of the patients, the operator, and the radiographic evaluator was not feasible.
Clinical Intervention Inferior alveolar nerve block anesthesia was administered using 4% articaine with 1:100,000 epinephrine (Ultracain DS; Sanofi-Aventis, Germany). Following rubber dam isolation, all carious tissue was removed non-selectively under water cooling using a sterile high-speed diamond bur, and cavity preparation was completed with a sterile round bur mounted on a low-speed handpiece.
Subsequently, root canal treatment was performed according to the assigned group protocol, consisting of either 2.5% NaOCl and 17% EDTA as the final irrigation regimen, 2.5% NaOCl and 9% HEBP as the final irrigation regimen, or 2.5% NaOCl and 9% HEBP used both during canal preparation and as the final irrigation solution.
Irrigation Procedures Group I: Final Irrigation with 2.5% NaOCl and 17% EDTA After access cavity preparation, the working length (WL) was determined using an electronic apex locator (Root ZX; Morita, Tokyo, Japan) and confirmed radiographically. Following glide path preparation, the root canals were shaped to the working length using Reciproc files (VDW, Munich, Germany) according to the manufacturer's instructions, employing a crown-down preparation technique. During canal instrumentation, irrigation was performed with a total volume of 20 mL of 2.5% NaOCl. Upon completion of canal preparation, irrigation was carried out sequentially with 10 mL of distilled water, 3 mL of 17% EDTA, 10 mL of distilled water, and a final rinse with 2 mL of 2.5% NaOCl.
Group II: Final Irrigation with 2.5% NaOCl and 9% HEBP After access cavity preparation, the working length was determined using an electronic apex locator and confirmed radiographically. Following glide path preparation, root canal shaping was performed to the working length using Reciproc files in accordance with the manufacturer's recommendations and a crown-down technique. During canal preparation, irrigation was performed using a total of 20 mL of 2.5% NaOCl. After instrumentation, the canals were irrigated with 10 mL of distilled water, followed by final irrigation with 5 mL of a solution containing 2.5% NaOCl and 9% HEBP.
Group III: Irrigation with 2.5% NaOCl-9% HEBP During Both Preparation and Final Irrigation After access cavity preparation, the working length was established using an electronic apex locator and confirmed radiographically. Glide path preparation was followed by canal shaping to the working length using Reciproc files with a crown-down technique. Throughout both canal preparation and final irrigation, a total of 25 mL of a solution containing 2.5% NaOCl and 9% HEBP was used for irrigation.
Root Canal Obturation Following completion of the irrigation procedures, the root canals were dried with sterile paper points and obturated using gutta-percha cones in combination with a calcium silicate-based sealer, employing the cold lateral condensation technique. A postoperative periapical radiograph was obtained after obturation. Teeth exhibiting overfilling beyond the radiographic apex or obturation terminating more than 2 mm short of the apex were excluded from the study.
Final Restoration A 3-mm-thick layer of flowable composite resin was placed in the pulp chamber. The remaining coronal restoration was completed using composite resin with an incremental layering technique. After removal of the rubber dam, occlusal adjustments were performed, and the restoration was finished and polished during the same appointment. Immediate postoperative periapical radiographs were then obtained.
Patients were instructed to return for follow-up examinations at 3, 6, and 12 months, or earlier if any symptoms occurred.
Postoperative Pain Management For postoperative pain control, patients were prescribed 400 mg ibuprofen tablets to be taken as needed. Patients were instructed to record the frequency of analgesic intake in writing. In cases of severe postoperative pain not relieved by analgesics, patients were advised to contact the operator immediately.
Evaluation Criteria and Follow-up Examinations Clinical and Radiographic Follow-up Patients were recalled at 3, 6, and 12 months for clinical and radiographic examinations. At each follow-up visit, the clinical and radiographic outcomes of the treated teeth were recorded.
Clinical Success Criteria
Clinical success was defined as:
Absence of spontaneous pain or discomfort, except during the initial postoperative days; Absence of tooth mobility greater than Grade I; Normal periradicular soft tissues without swelling or sinus tract formation; Negative responses to axial palpation and percussion tests. Radiographic Success Criteria
Radiographic success was defined as:
No increase in the Periapical Index (PAI) score at follow-up; Absence of extra-radicular or intra-radicular pathology; No evidence of internal or external root resorption. Additional Assessments The integrity of the coronal restoration was evaluated at each follow-up visit, and any need for replacement or re-restoration was recorded. Additionally, the presence of clinical symptoms, including percussion sensitivity, sinus tract formation, and extraoral abscess, was assessed at all follow-up appointments.
- Conditions
- Chronic Apical Periodontitis
- Being tested
- Final irrigation with 2.5% NaOCl and 17% EDTA, Final irrigation with 2.5% NaOCl and 9% HEBP, Irrigation with 2.5% NaOCl-9% HEBP during both preparation and final irrigation
- Keywords
- Etidronic acid (HEBP), Ethylenediaminetetraacetic acid (EDTA), Sequential chelation, Consecutive chelation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Final irrigation with 2.5% NaOCl and 17% EDTAProcedure or surgery
During canal preparation, irrigation will be performed with a total of 20 mL of 2.5% NaOCl. After completion of preparation, irrigation will be carried out with 10 mL of distilled water, followed by sequential irrigation with 3 mL of 17% EDTA, 10 mL of distilled water, and 2 mL of 2.5% NaOCl.
Final irrigation with 2.5% NaOCl and 9% HEBPProcedure or surgery
During canal preparation, irrigation will be performed with a total of 20 mL of 2.5% NaOCl. After completion of preparation, irrigation will be carried out with 10 mL of distilled water, followed by final irrigation with 5 mL of 2.5% NaOCl-9% HEBP.
Irrigation with 2.5% NaOCl-9% HEBP during both preparation and final irrigationProcedure or surgery
During both canal preparation and final irrigation, a total of 25 mL of 2.5% NaOCl-9% HEBP will be used for irrigation.
| Study group | Role | What they receive |
|---|---|---|
| Group I: Final irrigation with 2.5% NaOCl and 17% EDTA | Active comparator | After preparation of the access cavity the working length (WL) will be determined using an electronic apex locator (Root ZX [Morita, Tokyo, Japan]) and confirmed radiographically. Following glide path preparation, the root canals will be shaped to the working length using a Resiproc files (VDW, Munich, Germany) in accordance with the manufacturer's instructions, employing the crown-down preparation technique.
During canal preparation, irrigation will be performed with a total of 20 mL of 2.5% NaOCl. After completion of preparation, irrigation will be carried out with 10 mL of distilled water, followed by sequential irrigation with 3 mL of 17% EDTA, 10 mL of distilled water, and 2 mL of 2.5% NaOCl. Receives: Procedure: Final irrigation with 2.5% NaOCl and 17% EDTA |
| Group II: Final irrigation with 2.5% NaOCl and 9% HEBP | Experimental | After preparation of the access cavity, the working length (WL) will be determined using an electronic apex locator (Root ZX [Morita, Tokyo, Japan]) and confirmed radiographically. Following glide path preparation, the root canals will be shaped to the working length using a Resiproc files (VDW, Munich, Germany) in accordance with the manufacturer's instructions, employing the crown-down preparation technique.
During canal preparation, irrigation will be performed with a total of 20 mL of 2.5% NaOCl. After completion of preparation, irrigation will be carried out with 10 mL of distilled water, followed by final irrigation with 5 mL of 2.5% NaOCl-9% HEBP. Receives: Procedure: Final irrigation with 2.5% NaOCl and 9% HEBP |
| Group III: Irrigation with 2.5% NaOCl-9% HEBP during both preparation and final irrigation | Experimental | After preparation of the access cavity, the working length (WL) will be determined using an electronic apex locator (Root ZX [Morita, Tokyo, Japan]) and confirmed radiographically. Following glide path preparation, the root canals will be shaped to the working length using a Resiproc files (VDW, Munich, Germany) in accordance with the manufacturer's instructions, employing the crown-down preparation technique.
During both canal preparation and final irrigation, a total of 25 mL of 2.5% NaOCl-9% HEBP will be used for irrigation. Receives: Procedure: Irrigation with 2.5% NaOCl-9% HEBP during both preparation and final irrigation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Periapical Lesion Healing
Radiographic periapical status assessed using the Periapical Index (PAI) according to Ørstavik et al., with scores ranging from 1 (normal periapical structures) to 5 (severe apical periodontitis), based on the degree of periapical radiolucency. The primary outcome will be periapical lesion healing, evaluated by changes in periapical index (PAI) scores on periapical radiographs taken before treatment and at the 12-month follow-up.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2026
- Study start1 Dec 2025
- Primary completionApr 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Chronic Apical PeriodontitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is designed as a prospective, parallel-group, double-blind, randomized controlled clinical trial.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 63 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mustafa Kemal University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Merve Sari, Mustafa Kemal University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07353008
- Sponsor's protocol ID
- 2801
- Status last verified
- Jan 2026
- First submitted
- 13 Jan 2026
- Last updated
- 23 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share IPD due to confidentiality and privacy considerations.
Publications
Campello AF, Rodrigues RCV, Alves FRF, Miranda KR, Brum SC, Mdala I, Siqueira JF Jr, Rocas IN. Enhancing the Intracanal Antibacterial Effects of Sodium Hypochlorite with Etidronic Acid or Citric Acid. J Endod. 2022 Sep;48(9):1161-1168. doi: 10.1016/j.joen.2022.06.006. Epub 2022 Jun 22.
PubMed 35750221Hazar E, Hazar A. Effects of phytic acid and etidronic acid using continuous and sequential chelation on the removal of smear layer, dentin microhardness, and push-out bond strength of calcium silicate-based cement. BMC Oral Health. 2025 Apr 24;25(1):633. doi: 10.1186/s12903-025-06010-5.
PubMed 40275217Tartari T, Wilchenski BS, de Souza Lima LA, Vivan RR, Ballal V, Duarte MAH. The use of sodium hypochlorite mixed with etidronic acid during canal preparation increases debris extrusion. Aust Endod J. 2023 Dec;49(3):584-591. doi: 10.1111/aej.12788. Epub 2023 Aug 11.
PubMed 37571801Razumova S, Brago A, Kryuchkova A, Troitskiy V, Bragunova R, Barakat H. Evaluation of the efficiency of smear layer removal during endodontic treatment using scanning electron microscopy: an in vitro study. BMC Oral Health. 2025 Jan 28;25(1):151. doi: 10.1186/s12903-025-05510-8.
PubMed 39875846Pandya DS, Kritika S, Sanjeev K, Mahalaxmi S, Neelakantan P. Endotoxin Levels after Calcium Hydroxide Placement in Root Canals Irrigated with Continuous or Sequential Chelation in Previously Treated Teeth with Symptomatic Apical Periodontitis: A Randomized Controlled Clinical Trial. J Endod. 2025 Nov;51(11):1519-1525. doi: 10.1016/j.joen.2025.08.004. Epub 2025 Aug 18.
PubMed 40835176