3Mixtatin Versus Modified 3Mix-MP in Lesion Sterilization and Tissue Repair for Treatment of Necrotic Primary Molars

Study Overview
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Brief Summary
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This randomized clinical study aims to assess the clinical and radiographic success rate of the 3Mixtatin versus the 3Mix in LSTR in necrotic primary molars.

Detailed Description
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Research question: In necrotic primary molars with peri-radicular lesions and/or external root, resorption does adding Simvastatin to the triple antibiotic mix have higher clinical and radiographic success than the triple antibiotic paste solely? Statement of the problem: Primary teeth with necrotic pulp and extensive root resorption and/or furcal radiolucency are not uncommon scenarios that pediatric dentists are exposed to. Such clinical and radiographic presentations contraindicate the application of conventional pulpectomy treatment. Lesion Sterilization and Tissue Repair (LSTR) is an approach that has shown promising results in maintaining such teeth for up to 12 months. Primary teeth serve as a natural space maintainer, enable normal and healthy functioning of the child, and eliminate the chances for malocclusion and growth pattern disruptions. LSTR offers practitioners a promising option to save those teeth when all other treatment options seem impossible. The Rationale for Conducting the Research: In accordance to the popularity that LSTR has recently been gaining in the field of Pediatric dentistry, an abundance of studies have been conducted in the recent years. Researchers are striving to explore the plethora of possibilities and variances in the LSTR technique that could help clinicians practice better and achieve more for their patients. Amongst the alternatives is the recent and common detour towards regenerative dentistry. Simvastatin, one of the materials, remains of high interest to the field due to its healing powers. However, to our knowledge insufficient studies are available on the direct comparison of the clinical and radiographic success including bone regeneration using the 3Mixtatin versus 3Mix alone. Furthermore, studies conducted warrant the need for further studies directly comparing 3Mixtatin with 3mix. Therefore, this study aims to come to a conclusion on whether the 3mix with the host's body defense and repair mechanism are sufficient to save a necrotic primary tooth or is some help in bone regeneration and healing promotion needed. The LSTR technique involves non-instrumentation or minimal instrumentation followed by sterilization of the infected pulpal space by the placement of a triple antibiotic mixture in a propylene glycol vehicle to disinfect the microbial flora inhabiting the infected root canal systems and peri-apical lesions. The latter step achieves disinfection while tissue repair is then allowed to take place by the host's natural body defense mechanisms The triple antibiotic paste (TAP/3mix), is an intracanal medicament that has continuously proven its efficacy and superiority for years against the microflora inhabiting necrotic canals predominantly Enterococcus Faecalis, the most prevalent organism in infected root canals. Metronidazole, ciprofloxacin, and minocycline, the oldest and most common combination suggested by Takushige et al., has been subjected to many studies and changes due to the discoloration caused by minocycline. As a result of, modified triple antibiotic paste (Modified-3mix) was introduced to replace minocycline with clindamycin. Statins are antihyperlipidemic drugs, with a bio inductive feature that includes inhibition of bone resorption and promotion of osteoblast proliferation and differentiation as well as stimulating angiogenesis all of which aid in the healing process. In a clinical trial mixing modified 3mix with statins in, namely, Simvastatin; resulted in excellent clinical and radiographic success rates. Hence, modifying the LSTR technique to include regenerative materials such as statin is an extremely promising area of research.

Official Title
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A Randomized Controlled Trial Comparing the Clinical and Radiographic Success of 3Mixtatin Versus Modified 3Mix in Lesion Sterilization and Tissue Repair (LSTR) for The Treatment of Necrotic Primary Molars

Conditions
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Necrotic Primary Molars

Intervention / Treatment
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* Drug: 3Mixtatin paste: Simvastatin mixed with modified triple antibiotic
* Drug: 3Mix: Modified triple antibiotic mix in propylene glycol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients aged 4-7 years. Positive parental informed consent. Restorable necrotic mandibular second primary molars with peri-radicular/furcal involvement and/or pathologic root resorption (external or internal). Presence of chronic apical abscess or sinus tract or furcation radiolucency. (Thakur et al., 2021) Exclusion Criteria: Medically compromised children. Children with known allergy to any of the components being utilized. Molars near exfoliation. Molars with severely resorbed roots more than two thirds indicated for extraction Molars with insufficient coronal structure disabling proper coronal seal. Presence of periapical or interradicular radiolucent area which could compromise the permanent tooth bud. (Shetty et al., 2020)

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (Group I Experimental Group):Simvastatin mixed with modified triple antibiotic (3Mixtatin)<br>Patients will then be allocated into either one of the groups alternatively after access cavity preparation depending on the mix to be used as follows: for this group: 2mg of pure Simvastatin powder will be added to the 1:1:1 3Mix powder and will be stored together in an air tight porcelain container to avoid the exposure to moisture and light. Upon clinical application the 3Mixtatin powder will be mixed with normal saline to form a paste and is then applied in the same manner as the Modified 3Mix-MP paste. | Drug: 3Mixtatin paste: Simvastatin mixed with modified triple antibiotic<br>* Drying the mucosa with gauze,topical anesthesia will be applied. Administration of local anesthesia with vasoconstrictor. Rubber dam isolation. Caries removal & access cavity using a round bur mounted on a high-speed contra with coolant. Removal of necrotic pulp tissue in coronal portion of the tooth using sharp excavator. Radicular section will be kept untouched,no instrumentation. Using disposable syringe Irrigation of the pulp chamber with 2.5% NaOCl. In case of hemorrhage moist cotton immersed in 1% NaOCL will be placed to achieve hemostasis. Drying the access cavity with sterile cotton pellets. Freshly mixed 3Mix-MP or 3Mixtatin paste (according to group of intervention) will be transferred to the floor of the pulp chamber using an amalgam carrier & condensed over orifices using a moist cotton pellet. Cavity sealing with RMGI capsules. Same visit placement with preformed Stainless-steel crown(3M® ESPE)cemented with glass ionomer cement.<br>|
| Active Comparator: Group II Control group Modified triple antibiotic mix in propylene glycol (3Mix)<br>Removal of enteric coating/capsule of the three antibiotic tablets using a surgical blade. 500 mg Metronidazole tab 500 mg Ciprofloxacin tab 200 mg Cefixime caps Pulverization of each of the drug, will be done using a pestle & mortar, stored in an air tight porcelain container to avoid the exposure to moisture & light. Pulverized powders will be stored at a temperature of 16°C.Powder should be allowed to be cooled to the room temperature before initiating the preparation of 3Mix-MP paste. Powders will be mixed in the proportion of: 1:1:1 by volume (Hoshino et al., 1988). Vehicle that will be used is Systane eye drops (Kharadly et al., 2022) it contains the two main components propylene Glycol (Macrogol) & polyethylene glycol. The prepared antibiotic powder is mixed with the prepared vehicle in the ratio of 7:1 by volume. The two steps above are done after access cavity preparation to obtain a fresh mix. | Drug: 3Mix: Modified triple antibiotic mix in propylene glycol<br>* Drying the mucosa with gauze,topical anesthesia will be applied. Administration of local anesthesia with vasoconstrictor. Rubber dam isolation. Caries removal & access cavity using a round bur mounted on a high-speed contra with coolant. Removal of necrotic pulp tissue in coronal portion of the tooth using sharp excavator. Radicular section will be kept untouched,no instrumentation. Using disposable syringe Irrigation of the pulp chamber with 2.5% NaOCl. In case of hemorrhage moist cotton immersed in 1% NaOCL will be placed to achieve hemostasis. Drying the access cavity with sterile cotton pellets. Freshly mixed 3Mix-MP or 3Mixtatin paste (according to group of intervention) will be transferred to the floor of the pulp chamber using an amalgam carrier & condensed over orifices using a moist cotton pellet. Cavity sealing with RMGI capsules. Same visit placement with preformed Stainless-steel crown(3M® ESPE)cemented with glass ionomer cement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of pathological mobility measured by (Miller's grades) | Miller's Classification Grade I: first distinguishable sign of movement Grade II: movement of tooth which allows crown to deviate 1mm of its normal position Grade III shows noticeable and increased movement of tooth more than 1mm in any direction or the tooth can be depressed into the socket. A reduction in grade of mobility from preoperative baseline will be considered as success while increased mobility will be recorded as failure | baseline | 
| Absence of pathological mobility measured by (Miller's grades) | Miller's Classification Grade I: first distinguishable sign of movement Grade II: movement of tooth which allows crown to deviate 1mm of its normal position Grade III shows noticeable and increased movement of tooth more than 1mm in any direction or the tooth can be depressed into the socket. A reduction in grade of mobility from preoperative baseline will be considered as success while increased mobility will be recorded as failure | at 3 months post operative | 
| Absence of pathological mobility measured by (Miller's grades) | Miller's Classification Grade I: first distinguishable sign of movement Grade II: movement of tooth which allows crown to deviate 1mm of its normal position Grade III shows noticeable and increased movement of tooth more than 1mm in any direction or the tooth can be depressed into the socket. A reduction in grade of mobility from preoperative baseline will be considered as success while increased mobility will be recorded as failure | at 6 months post operative | 
| Absence of pathological mobility measured by (Miller's grades) | Miller's Classification Grade I: first distinguishable sign of movement Grade II: movement of tooth which allows crown to deviate 1mm of its normal position Grade III shows noticeable and increased movement of tooth more than 1mm in any direction or the tooth can be depressed into the socket. A reduction in grade of mobility from preoperative baseline will be considered as success while increased mobility will be recorded as failure | at 12 months post operative | 
| Absence of post-operative pain (binary) | Measured by asking the patient to identify presence or absence of pain | baseline | 
| Absence of post-operative pain (binary) | Measured by asking the patient to identify presence or absence of pain | at 3 months post operative | 
| Absence of post-operative pain (binary) | Measured by asking the patient to identify presence or absence of pain | at 6 months post operative | 
| Absence of post-operative pain (binary) | Measured by asking the patient to identify presence or absence of pain | at 12 months post operative | 
| Absence of soft tissue pathologies (binary) | Binary outcome measured visually by intraoral/extraoral examination | baseline | 
| Absence of soft tissue pathologies (binary) | Binary outcome measured visually by intraoral/extraoral examination | at 3 months post operative | 
| Absence of soft tissue pathologies (binary) | Binary outcome measured visually by intraoral/extraoral examination | at 6 months post operative | 
| Absence of soft tissue pathologies (binary) | Binary outcome measured visually by intraoral/extraoral examination | at 12 months post operative | 
| Absence of pain on percussion (binary) | Binary outcome measured by gentle tapping using the back of the mirror on the tooth | baseline | 
| Absence of pain on percussion (binary) | Binary outcome measured by gentle tapping using the back of the mirror on the tooth | at 3 months post operative | 
| Absence of pain on percussion (binary) | Binary outcome measured by gentle tapping using the back of the mirror on the tooth | at 6 months post operative | 
| Absence of pain on percussion (binary) | Binary outcome measured by gentle tapping using the back of the mirror on the tooth | at 12 months post operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Status of radiolucency if present at the periapical or at furcation area | Comparison between pre-operative radiolucency and at follow up periods post-operatively to asses bone regeneration. Results will be recorded as Static-Increased-Decreased using customized stent for xray and Digora software for measurements. | baseline | 
| Status of radiolucency if present at the periapical or at furcation area | Comparison between pre-operative radiolucency and at follow up periods post-operatively to asses bone regeneration. Results will be recorded as Static-Increased-Decreased using customized stent for xray and Digora software for measurements. | at 6 months post operative | 
| Status of radiolucency if present at the periapical or at furcation area | Comparison between pre-operative radiolucency and at follow up periods post-operatively to asses bone regeneration. Results will be recorded as Static-Increased-Decreased using customized stent for xray and Digora software for measurements. | at 12 months post operative | 
| Absence of external or internal root resorption | Binary outcome measured by comparing pre-operative x-ray with baseline and follow up x-rays. using customized stent | baseline , 6 ,12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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3MIX-MP, 3Mixtatin, LSTR