Objectives: The objectives of this study were to estimate and compare the 1-year clinical success rates of triple antibiotic paste (TAP), double antibiotic paste (DAP), calcium hydroxide (CH) within regenerative endodontic procedures (REPs) on permanent necrotic immature teeth. Materials and Methods: Trials investigating REP success were searched through MEDLINE, Scopus, Embase, Web of Science, GOOGLE Scholar (last update December 2025). Primary study quality was evaluated through the revised Cochrane Risk of Bias tool for Randomised Trials (RoB2). Pooled success rates with 95% confidence intervals (95% CIs) were assessed. Heterogeneity was investigated with the Cochran's Q and quantified with I2: The random-effects model was preferred to the fixed-effect model for I2 > 50%. Sensitivity (study quality, publication bias, study inclusion) and subgroup (scaffold type, world Region) analyses were made. The differences in pooled success rates between protocols were assessed and were evaluated using an equivalence range of −2.5%/+2.5%. The GRADE system was employed to evaluate the Quality of Evidence of the pooled success rates. Results: Twenty-four studies of average quality were included involving 544, 64, 183 patients, for TAP, DAP, CH, respectively. The pooled success rates (tooth survival after 1 year with periapical healing, absence of signs and symptoms of pathology) were TAP 96.7% (95% CI, 94.8%–98.0%), DAP 84.2% (95% CI, 73.2%–92.0%), CH 97.4% (95% CI, 93.9%–99.1%). The pooled differences in success rates were TAP-DAP 12.5% (95% CI, 2.8%–22.1%, TAP superiority demonstrated), TAP-CH −0.7% (95% CI, −0.9%–2.5%, TAP/CH equivalence demonstrated), CH-DAP 13.2% (95% CI, 3.3%–23.0%, CH superiority demonstrated). Secondary analyses corroborated these results, although the overall statistical test power was low due to small sample sizes. The GRADE quality of evidence was high for TAP and CH, and low for DAP, due to substantial imprecision attributed to the small number of studies with small sample sizes. Conclusions: The lack of direct comparisons between protocols and of a common comparator did not allow for more robust analyses. Nevertheless, the use of TAP and CH as intracanal medicament within REPs resulted equivalent in eradicating the infection and promoting periapical healing in permanent necrotic immature teeth at 1-year follow up, and these protocols resulted superior over DAP. Registration: PROSPERO registration number: CRD42023484189.
The Efficacy of Intracanal Medicaments Within the Regenerative Endodontic Procedures on Permanent Necrotic Immature Teeth: Systematic Review and Naïve Indirect‐Comparison Meta‐Analysis
Alovisi, Mario;Arduino, Paolo G.;
2026-01-01
Abstract
Objectives: The objectives of this study were to estimate and compare the 1-year clinical success rates of triple antibiotic paste (TAP), double antibiotic paste (DAP), calcium hydroxide (CH) within regenerative endodontic procedures (REPs) on permanent necrotic immature teeth. Materials and Methods: Trials investigating REP success were searched through MEDLINE, Scopus, Embase, Web of Science, GOOGLE Scholar (last update December 2025). Primary study quality was evaluated through the revised Cochrane Risk of Bias tool for Randomised Trials (RoB2). Pooled success rates with 95% confidence intervals (95% CIs) were assessed. Heterogeneity was investigated with the Cochran's Q and quantified with I2: The random-effects model was preferred to the fixed-effect model for I2 > 50%. Sensitivity (study quality, publication bias, study inclusion) and subgroup (scaffold type, world Region) analyses were made. The differences in pooled success rates between protocols were assessed and were evaluated using an equivalence range of −2.5%/+2.5%. The GRADE system was employed to evaluate the Quality of Evidence of the pooled success rates. Results: Twenty-four studies of average quality were included involving 544, 64, 183 patients, for TAP, DAP, CH, respectively. The pooled success rates (tooth survival after 1 year with periapical healing, absence of signs and symptoms of pathology) were TAP 96.7% (95% CI, 94.8%–98.0%), DAP 84.2% (95% CI, 73.2%–92.0%), CH 97.4% (95% CI, 93.9%–99.1%). The pooled differences in success rates were TAP-DAP 12.5% (95% CI, 2.8%–22.1%, TAP superiority demonstrated), TAP-CH −0.7% (95% CI, −0.9%–2.5%, TAP/CH equivalence demonstrated), CH-DAP 13.2% (95% CI, 3.3%–23.0%, CH superiority demonstrated). Secondary analyses corroborated these results, although the overall statistical test power was low due to small sample sizes. The GRADE quality of evidence was high for TAP and CH, and low for DAP, due to substantial imprecision attributed to the small number of studies with small sample sizes. Conclusions: The lack of direct comparisons between protocols and of a common comparator did not allow for more robust analyses. Nevertheless, the use of TAP and CH as intracanal medicament within REPs resulted equivalent in eradicating the infection and promoting periapical healing in permanent necrotic immature teeth at 1-year follow up, and these protocols resulted superior over DAP. Registration: PROSPERO registration number: CRD42023484189.
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