Therapeutic Irrigant Procedures for Treating Apical Periodontitis (TIPTAP): A triple-blinded parallel-group randomized controlled phase I/II trial

Background

Solubilized endogenous dentine extracellular matrix components (dECMs) are potent mediators in pulp regeneration and could potentially promote similar healing effects in diseased periradicular tissues by upregulating local mesenchymal stem cell-derived regenerative events.

Aims

(1) Determine if endodontic treatment outcomes with irrigation regimes promoting dECM release (17% ethylenediaminetetraacetic acid [EDTA]) are equivalent to conventional regimes (5.25% sodium hypochlorite [NaOCl]) in mature permanent teeth with asymptomatic apical periodontitis. (2) Explore changes in pain scores, expressions of periradicular tissue fluid (PTF)-derived inflammatory mediators, and volumtric changes in lesion size between the different irrigant regimes.

Methods

Forty single-rooted teeth, from 37 healthy adults, were block randomized into parallel groups of irrigation with either 17% EDTA, optimized for dECM solubilization, or 5.25% NaOCl (n = 20). All other aspects of the endodontic protocol were standardized over two visits with 14 days of calcium hydroxide intracanal medicament. Patient-reported pain scores were recorded at six hours and then daily for one week post-instrumentation and post-obturation. PTF samples were collected pre-instrumentation and pre-obturation, where analyte profiles (pg/TPC) were determined using an O-link Target-48 cytokine array. Treatment outcomes were clinically and radiographically assessed with cone beam computed tomography at 1 year using dichotomous criteria (favourable/unfavourable) based on volumetric change in lesion size. Participants, operators and assessors were blinded, and per-protocol analyses were conducted using binary logistic regression models with initial alpha values for statistical comparisons set at p < .05.

Results

A 90% recall rate was achieved at one year (NaOCl: 19; EDTA: 17). Favourable outcomes were observed in 89.5% of treatments using NaOCl and 94.1% of treatments using EDTA irrigation, with median lesion volume reductions of 92.5% (IQR: 67.33–99.13) and 95.84% (IQR: 78.81–100), respectively, (p > .05). Odds of unfavourable periradicular healing with EDTA irrigation were 0.53 [95% CI: 0.04–6.44; p > .05]. No serious adverse effects or atypical pain patterns were reported, although two acute exacerbations occurred post-instrumentation with NaOCl irrigation (p > .05). Target-48 panels consistently detected 15 inflammatory analytes in both groups (CCL-2, -3, -4; CSF-1; CXCL-8; HGF; IL-1β, -6, -18; MMP-1, -12; OLR-1; OSM; TNFSF-10; VEGF-A), all of which reduced pre-obturation. At this stage, IL-6 and -18 were significantly more abundant in the intervention group (p < .05).

Conclusions

Therapeutic irrigant regimes promoting dECM solubilization resulted in one-year treatment outcomes equivalent to conventional irrigant protocols with no serious adverse effects reported.