Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2026 Mar 12.
doi: 10.1111/iej.70135. Online ahead of print.

The Efficacy of Intracanal Medicaments Within the Regenerative Endodontic Procedures on Permanent Necrotic Immature Teeth: Systematic Review and Naïve Indirect-Comparison Meta-Analysis

Mario Alovisi  1 , Paolo G Arduino  1 , Stefano Petti  2
Affiliations
Review

The Efficacy of Intracanal Medicaments Within the Regenerative Endodontic Procedures on Permanent Necrotic Immature Teeth: Systematic Review and Naïve Indirect-Comparison Meta-Analysis

Mario Alovisi et al. Int Endod J. .

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.

Keywords: calcium hydroxide; meta‐analysis; regenerative endodontic procedures; root canal disinfection; systematic review; triple antibiotic paste.

PubMed Disclaimer

References

    1. AAE. 2021. AAE Clinical Considerations for a Regenerative Procedure [EB/OL]. https://f3f142zs0k2w1kg84k5p9i1o‐wpengine.netdna‐ssl.com/specialty/wp‐content/uploads/sites/2/2021/08/ClinicalConsiderati....
    1. Acuna, S. A., F. Dossa, and N. Baxter. 2020. “Meta‐Analysis of Noninferiority and Equivalence Trials: Ignoring Trial Design Leads to Differing and Possibly Misleading Conclusions.” Journal of Clinical Epidemiology 127: 134–141. https://doi.org/10.1016/j.jclinepi.2020.05.034.
    1. Ahmed, H. M. A., V. Nagendrababu, H. F. Duncan, O. A. Peters, and P. M. H. Dummer. 2023. “Developing a Consensus‐Based Glossary of Controversial Terms in Endodontology.” International Endodontic Journal 56, no. 7: 788–791. https://doi.org/10.1111/iej.13918.
    1. Alagl, A., S. Bedi, K. Hassan, and J. AlHumaid. 2017. “Use of Platelet‐Rich Plasma for Regeneration in Non‐Vital Immature Permanent Teeth: Clinical and Cone‐Beam Computed Tomography Evaluation.” Journal of International Medical Research 45, no. 2: 583–593. https://doi.org/10.1177/0300060517692935.
    1. Almutairi, W., G. H. Yassen, A. Aminoshariae, K. A. Williams, and A. Mickel. 2019. “Regenerative Endodontics: A Systematic Analysis of the Failed Cases.” Journal of Endodontics 45, no. 5: 567–577. https://doi.org/10.1016/j.joen.2019.02.004.

LinkOut - more resources