Effectiveness of Regenerative Endodontics Therapy for Single-rooted Mature Permanent Tooth With Pulp Necrosis

Study Overview
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Brief Summary
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This study is to evaluate the effectiveness of regenerative endodontics therapy in single-rooted permanent teeth with pulp necrosis，and compare the clinical efficacy of platelet rich fibrin (PRF) and blood clot (BC) as scaffolds.

Detailed Description
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Regenerative endodontics therapy (RET), based on the principles of tissue engineering, manipulates stem cells, scaffold, and bioactive growth factors to achieve the functional reconstruction of pulp tissue. RET has been recommended strongly as an alternative in treating immature permanent teeth with necrotic pulp in recent years, while root canal therapy (RCT) has been extensively applied in the treatment of mature permanent teeth with necrotic pulp. RCT contains the chemomechanical preparation of the infected root canals to eliminate the microorganisms, and root canal obturation with filling materials to reduce and prevent microbial contamination in root canal system. However, the root canal filling materials, such as Gutta-percha, are inert materials which fail to recover the physiological function of the pulp. As RET has been proved curative for immature permanent teeth diagnosed with pulp necrosis, doctors and researchers try to extend its application in the mature ones. Encouragingly, several RET cases for mature teeth reported in the literature have shown positive clinical outcomes. However, it still lacks long-term and well-designed randomized clinical trial with large sample size and following standardized protocol, hence this study is conducted to make up for it to achieve high-level evidence. In the process of RET, the scaffold can provide nutrition and space, which are essential for the proliferation and differentiation of stem cells. Therefore, it is a crucial step to select a high-quality material as the scaffold. In many studies of RET procedures, blood clot (BC), generated by provoking apical bleeding into the root canal, is regarded as a scaffold. Nevertheless, it remains a common problem that operators may fail to induce apical bleeding or achieve adequate blood volume. Recent studies suggest that patelet rich fibrin (PRF), the second-generation platelet concentrate, can provide a fibrin network full of cytokines and growth factors, which may improve the desired biological outcome. Accordingly, we assumed that PRF could improve the curative effect for mature teeth in RET. The purpose of this study is to compare the clinical efficacy of PRF and BC as scaffolds in RET for the mature permanent tooth with pulp necrosis.

Official Title
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Effectiveness of Regenerative Endodontics Therapy for Single-rooted Mature Permanent Tooth With Pulp Necrosis: a Multicenter Randomized Controlled Clinical Trial.

Conditions
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Pulp Necrosis

Intervention / Treatment
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* Other: PRF
* Other: BC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Intended to participate with this study, and provide informed assent/consent. Aged 10 and 59 years. At least one mature permanent teeth diagnosed as pulp necrosis with or without periapical lesion, and CBCT showed the teeth has single root and single root canal. Exclusion Criteria: Allergic to any medications or materials necessary to complete the procedures. The teeth with severe coronal defect, of which pulp space is needed for post/core final restoration. Non-restorable teeth. The teeth with root fracture or vertical root fractures. Concurrent signs of other pathological root resorption. Patients with periodontitis. Patients with dental dysplasia or other oral genetic disorders. Women who are pregnant or lactating, or women who plan to become pregnant in the subsequent 2 years. Patients with dental phobia. Patients with mental disorders. Patients with a history of systemic diseases that may alter immune function. Patients with medical conditions and/or receiving medications that would affect patients' body's ability of healing or blood clotting. Participants who are participating in or had participated in other clinical studies within the prior 3 months.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regenerative endodontics therapy with PRF<br>In the procedures of regenerative endodontics therapy, K-files were intentionally used to violate the periapical tissues via overinstrumentation up to 2-3mm past the apical foramen to induce bleeding. Only the apex 1/3 of the root canal need to be filled with blood. PRF was injected into the root canal to a level below the CEJ, then wait for 10-15min to coagulate. | Other: PRF<br>* A sample of whole venous blood was drawn from the patient's forearm. The blood sample was transferred into a tube without anticoagulant and centrifuged immediately using a centrifuge.<br>|
| Active Comparator: Regenerative endodontics therapy with BC<br>In the procedures of regenerative endodontics therapy, K-files were intentionally used to violate the periapical tissues via overinstrumentation up to 2-3mm past the apical foramen to induce bleeding. The adequate blood need to be full with canal space and below the CEJ, then wait for 10-15min to coagulate. | Other: BC<br>* According to the procedures of regenerative endodontics therapy, BC was made by the way of provoking apical bleeding into root canal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success of regenerative endodontics therapy | Success: Defined as symptoms, clinical and radiographic assessment of the teeth. The teeth with RET were asymptomatic; Clinical examination showed absence of clinical signs of pain and soft tissue pathology (e.g. abscess, sinus tract etc.). Radiographic assessment showed the reduction and/or absence of periapical radiolucency. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulp vitality | Change in pulpal vitality will be assessed through pulpal response to sensitivity tests (cold, hot and electrical test) in teeth treated with RET. | 1、3、6、12、18、24 months | 
| Adverse events | Such as discoloration, reinfection, root resorption and so on. | 1、3、6、12、18、24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulp Necrosis, Regenerative Endodontics Therapy, Platelet Rich Fibrin