Non-instrumentation Root Canal Treatment of Primary Molars (EndoDecide-1)

Efficacy of Non-instrumentation Endodontic Treatment With an Antibiotic Mix Paste in Primary Molars: a Multicenter Randomized Clinical Trial With 2 Years of Follow-up

This randomized clinical trial intended to evaluate the efficacy of a technique of root canal treatment of deciduous molars with non-instrumentation of root canals and use of a paste containing antibiotics (chloramphenicol and tetracycline) and zinc oxide and eugenol (CTZ group). The hypothesis is that the efficacy of non-instrumentation treatment is non-inferior than the standard treatment involving manual instrumentation of root canals and filling with zinc oxide and eugenol paste (ZOE group) after 24 months of follow-up. Children will be randomly allocated to one of the two groups: CTZ group or ZOE group. In the CTZ group, after the location of root canals entrance, an initial irrigation will be conducted using 1% sodium hypochlorite. Then, CTZ paste will be placed in the pulp chamber floor, over the root canal entrances. The instrumentation of the root canals will not be performed for children allocated to this group. For the ZOE group, manual instrumentation with endodontic K files will be performed, aided by irrigation with 1% sodium hypochlorite. After the end of the instrumentation, root canals will be filled with ZOE paste. All teeth will be restored with bulk-fil resin composite. Children will be followed-up for 6, 12, 18 and 24 months after the treatment. The primary endpoint will be the success of endodontic treatment evaluated by clinical and radiographic methods after 24 months. Based on a non-inferiority limit of 15% in the success rate, it was estimated an anticipated sample size of 218 (109 per group), divided among the centers. Other secondary endpoints will be clinical time spent with the treatments, children's behavior during the treatment, discomfort immediately after the end of the treatment reported by the children, post-operative pain, improvement in the negative impact of Oral Health-Related Quality of Life, costs and cost-efficacy.

Most techniques for endodontic treatment in primary teeth require instrumentation of root canals and filling with an absorbable paste. This filling material could be pastes based on zinc oxide and eugenol, calcium hydroxide or iodoform, or filling materials composed by mixture of some of these components. This method, however, requires a long clinical time, which can be a challenge in the Pediatric Dentistry clinical practice. Therefore, some alternative techniques in which non-instrumentation is necessary have been purposed. The non-instrumentation technique most used in Brazil is a technique previously described, in 1964. This method involves the access to pulp chamber and removal of necrotic tissue with irrigation. After that, with no instrumentation of the root canals, a medicament containing zinc oxide and eugenol and two antibiotics, chloramphenicol and tetracycline, is placed in the entrance of the canals, and the restoration of the teeth is performed. Although the non-instrumentation methods for endodontic treatment of primary teeth are attractive and demand a short clinical time, strong evidence from well-conducted clinical trial lacks. Therefore, this four-center parallel-arms non-inferiority randomized clinical trial was designed to evaluate the efficacy of a non-instrumentation of root canals and use of a paste containing antibiotics (chloramphenicol and tetracycline) and zinc oxide and eugenol (CTZ) technique for endodontic treatment of primary molars. The hypothesis is that the efficacy of non-instrumentation treatment is non-inferior than the standard treatment involving manual instrumentation of root canals and filling with zinc oxide and eugenol (ZOE) paste after 24 months of follow-up. Children who look for dental treatment in one of four participant centers and with at least one primary molar requiring endodontic treatment will be eligible. If the child has more than one molar with pulp involvement, the included tooth will be determined by chance. Other teeth will be treated but they will not be included in the study. The participating centers are the dental schools of Santa Catarina Federal University, University of Sao Paulo, Rio de Janeiro State University and Iguaçu University. Included children will be randomly allocated to one of the two groups (allocation ratio of 1:1): CTZ group (non-instrumentation technique) and ZOE group (standard treatment). Randomization list will be generated in an appropriate website (www.sealedenvelopes.com), in permuted blocks (2, 4, and 8 samples) and stratified for the center. The sequence will be enclosed in individual opaque envelopes separated by the stratum. The disclosure of the allocated group will occur when the children will be seated in the dental chair, after the anesthesia, rubber dam isolation and opening of the tooth included for that child. Than the included tooth will be allocated to the CTZ group or to ZOE group. After the treatment, children will be followed-up for 6, 12, 18 and 24 months. Evidence of treatment failure in any period will be recorded, and the teeth will be extracted. The primary endpoint will be the success of the dental treatment after 24 months of follow-up (teeth with no evidence of failure in all follow-ups). The sample size calculation was estimated based on a success rate of 92% obtained in pulpectomies using ZOE from a previous systematic review (Coll et al., 2020), a non-inferiority limit of 15%, a significance level of 5% and statistical power of 90%. It was added 20% to this number to contemplate possible drop-outs and 60% due to the multi-center design. The anticipated sample size was 218 teeth (109 per group), divided among the centers. However, in March 2023, we decided to modify the original sample size from 218 to 200 participants, due to slower-than-anticipated recruitment. With this sample, considering the same parameters, we kept the statistical power around 90% (90.6%). Masking will not be possible for participants, operators, researchers or even outcome assessors due to the different nature of the treatments. However, the outcome assessor will not be informed the allocated group of each tooth. Other secondary endpoints will be the clinical time spent with the treatments, children's behavior during the treatment, discomfort immediately after the end of the treatment reported by the children, post-operative pain, short- and long-term improvement in the negative impact of Oral Health-Related Quality of Life, costs and cost-efficacy. The frequency of treatment success after 24 months will be compared between the groups in the intention-to-treat population considering the non-inferiority limit of 15% by the Miettinen-Nurminen's method. Sensitivity analysis will be conducted through non-inferiority Cox regression. For this, the period that the treatment failure occurred will be recorded. Secondary outcomes will be compared by proper statistical tests considering two-tailed hypothesis.

Non-instrumentation endodontic treatment and use of a paste containing two antibiotics (chloramphenicol and tetracycline) and zinc oxide and eugenol (CTZ paste)

After local anesthesia and rubber dam isolation, the pulp chamber will be accessed. After the location of root canals entrance, an initial irrigation will be conducted using 1% sodium hypochlorite. Then, a paste containing two antibiotics (chloramphenicol and tetracycline) and zinc oxide and eugenol (CTZ paste) will be placed in the pulp chamber floor, into the root canal entrances. Then, a layer of glass ionomer cement will be placed, and the teeth will be restored with bulk-fil resin composite.

After anesthesia and rubber dam isolation, pulp chamber will be accessed with burs, and the root canals entrance will be prepared using a Gates Glidden bur. The root canal length determination will be done subtracting 1 mm from the radiographic measurements performed on the different roots. The instrumentation will be performed with 21mm stainless steel endodontic hand K-files, with International Organization for Standardization (ISO) tip ranging from #08 to #35. Irrigation will be performed using 1% sodium hypochlorite. After the last file, a final irrigation will be conducted with ethylenediaminetetraacetic acid and tegentol (EDTA-T) and 0.9% sodium chloride solution, and the root canals will be dried with paper points. Then, the root canals will be filled with a Zinc Oxide and Eugenol paste (ZOE paste), inserted into the root canals with a lentulo spiral. A layer of glass ionomer cement will be placed, and the teeth will be restored with bulk-fil resin composite.

The success of the endodontic treatment is a dichotomous variable that will be defined through clinical and radiographic evaluation after 24 months. Clinical criteria for determining success will be the absence of fistula, edema, pain, pathological mobility, presence of periodontal health or physiological primary molar exfoliation. Radiographic signs of success will be: absence of bone rarefaction, or in the presence of previous endodontic lesion, reduction or non-evolution of this lesion, compatible root resorption with the eruptive phase, absence of pathological root resorption and presence of restorative material isolating the filling paste from the oral cavity. In the presence of any signs of failure in any period of follow-up, the treatment will be considered unsuccessful. The main comparisons between the groups will be done considering the frequency rate of success treatment 24 months after the treatment, when absence of failure was detected in all follow-ups.

The clinical operating time from the topical anesthesia to the removal of the rubber dam isolation after tooth restoration will be recorded with a digital chronometer by the dental assistant. The average time (quantitative variable) will be compared between the groups.

This outcome will be assessed during the treatment by an external researcher using the Frankl Scale, an ordinal scale classifying the behavior during the treatment with four categories varying from definitely negative behavior (score 1) to definitely positive behavior (score 4). This assessor will classify the children's behavior in the period between the topical anesthesia until to the removal of rubber dam isolation. This endpoint will be considered as a qualitative ordinal variable.

This variable will be reported by the participant using the Facial Image Scale, immediately after the end of the endodontic intervention. This is an ordinal scale with five representative faces ranging from a very sad and crying face (score 5) from a very happy and smiley face (score 1). Immediately after the end of the treatment, an external assessor will show the scale for the children and will ask: "Which of these faces reflects how you feel after treating your tooth?". The score related to the face that children indicated will be recorded. The outcome will be summarized and compared as a qualitative ordinal variable.

Two days after the endodontic treatment, the operator will make a phone call to the children's parents. The occurrence of postoperative pain will be evaluated through 3 questions that will be done by the assessor: Has your kid reported pain in the treated teeth (yes or no)? Has you noticed some edema (swelling) or fistula with pus (yes or no)?; and Did your kid need of analgesic medication intake (yes or no)?. These variables will be compared separately between the groups as dichotomous variables.

This outcome will be evaluated considering the scores obtained through a questionnaire to assess the Oral Health-Related Quality of Life (OHRQoL) answered by the children. The instrument that will be applied is the short-form of the Child Perceptions Questionnaire for children from 8 to 10 years old (CPQ 8-10) at the baseline, after the inclusion of the children (before the disclosure of the allocated group). The instrument has 16 questions, and five answer options are given for each question. A score ranging from 0 to 4 is given for each question, and the final score is obtained by the sum of all items. The higher the score obtained, the worse the OHRQoL. After 1 week of the end of the treatment, a new questionnaire will be applied. The mean of change scores and the effect sizes considering these two questionnaires will be compared between the groups.

In the 24 months follow-up period, a children will answer again the short version of the CPQ 8-10. The mean of change scores and the effect sizes considering these answers and the scores obtained with the instrument applied at the baseline will be compared between the groups.

This outcome will be evaluated considering the scores obtained through a questionnaire to assess the Children's Oral Health-Related Quality of Life (OHRQoL), using the answers by the parents as proxy. The instrument that will be applied is the Early Childhood Oral Health Impact Scale (ECOHIS) at the baseline, after the inclusion of the children (before the disclosure of the allocated group). The instrument has 13 questions, and six answer options are given for each question. A score ranging from 0 to 5 is given for each question, and the final score is obtained by the sum of all items. The higher the score obtained, the worse the OHRQoL. After 1 week of the end of the treatment, a new questionnaire will be applied. The mean of change scores and the effect sizes considering these two questionnaires will be compared between the groups.

In the 24 months follow-up period, the children's guardian who responded the ECOHIS at the baseline and one week after the intervention will answer again the ECOHIS. The mean of change scores and the effect sizes considering these answers and the scores obtained with the instrument applied at the baseline will be compared between the groups.

Costs of each procedure, with no considering the follow-up evaluations or failures, will be calculated per each tooth treated. In children with more than one tooth treated, the values will be multiplied by the number of treated teeth.

The costs of each treatment will be added to the cost of the failures and will be adjusted by the efficacy obtained with each treatment.

Inclusion Criteria: Children who look for dental treatment Children with at least one primary molar with clinical and/or radiographic signs of pulpal involvement Formal consent of the children's parents or legal guardians agreeing with the participation of the children Write or verbal assent of the children in participating of the study Exclusion Criteria: Children with special needs Children with report of allergy to the medications used in the pastes Children with a negative behavior in the inclusion session

The anonymous Individual Participating Data (IPD) containing baseline characteristics of the children and the teeth included, and results obtained for all primary and secondary endpoints, including appropriate dictionaries for the data will be shared in an institutional public repository of data after the acceptance of the manuscript containing the analysis of the primary endpoint (about 3 years after the inclusion of the first participant). The data will be shared as Excel Spreadsheet Format. The repository is the Institutional repository of scientific data of the University of São Paulo (repositorio.uspdigital.usp.br/) We will also share the descriptions of the Standard Operating Procedures created for two treatment groups as a text file, after the finish of the inclusions of the participants.

After the acceptance of the manuscript containing the main analysis of the primary outcome (about 3 years after the beginning of the study).

The access will be allowed for any researcher. Utilization of the data should be done with adequate citation of the original source.

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