Comparison of Anti-microbial Efficacy of Calcipex and Metapex in Endodontic Treatment of Chronic Apical Periodontitis
Condition: Chronic Apical Periodontitis
MeSH terms: Periodontitis; Periapical Periodontitis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Introduction:

      Pulpal necrosis may lead to spread of the infection from the pulp to involve the apex of the
      tooth and surrounding bone which when asymptomatic with periapical radiolucency on
      radiograph, is called chronic apical periodontitis. In order to eliminate the virulent
      bacteria and to overcome the inflammation in the root apex, endodontic treatment is the
      treatment of choice. Bacteria usually survive in the complex anatomy of the root canal
      system. In order to eliminate the remaining bacteria, various intracanal medicaments have
      been used widely however, there is controversy over their use and efficacy. Calcium hydroxide
      (CH) is the most commonly used intracanal medicament between root canal treatment sessions
      and available in different combinations. Multiple studies have been conducted to evaluate the
      effect of various types of CH based medicaments but whether CH with iodoform is more
      effective than CH alone against endodontic pathogens is a matter of controversy. In order to
      evaluate the true reduction in microbial load from the infected canals, microbial culture is
      a predictable and convenient tool.

      Thus, this study aims to evaluate the antimicrobial effectiveness of inter-appointment
      intracanal medicament with either CH alone (Calcipex) or CH with iodoform (Metapex) for the
      treatment of infected root canals of teeth diagnosed with chronic apical periodontitis using
      colony forming unit (CFU).

      Objective: To compare the anti-microbial efficacy of calcipex and metapex in endodontic
      treatment of teeth diagnosed with chronic apical periodontitis and to compare two different
      methods for removal of oil based intracanal medicaments.

      Method: Approval from ERC is obtained. The selected subjects will be divided in to two study
      groups using a computer generated randomization list i.e., Group A - Calcipex group (n = 30)
      and Group B - Metapex group (n = 30). Two samples will be collected from the root canals for
      evaluation of microbial load after chemomechanical preparation (S1) (before use of intracanal
      medicament) and after usage of intra canal medicament (S2)(after 7 days).

      Two techniques will be used for removal of oil based medicaments. Two radiographs will be
      obtained for each technique, after oil based medicament placement and after medicament
      removal for evaluation.

      Data Analysis: Mean and standard deviation of continuous variable will be computed. Frequency
      distribution and proportion of categorical variables will be determined. Paired t-test will
      be used to assess difference bet¬ween antimicrobial efficacies within groups of medicaments.
      Independent sample t-test will be used to assess antimicrobial efficacies between groups.
      Level of significance will be kept at 0.05.

      Mann whitney U test will be used to evaluate medicament removal between 2 groups and at three
      canal levels; coronal, middle and apical.
    

Detailed description: 
      This study aims to evaluate the antimicrobial effectiveness of inter-appointment intracanal
      medicament with either CH alone (Calcipex) or CH with iodoform (Metapex) for the treatment of
      infected root canals of teeth diagnosed with chronic apical periodontitis.

      And, to compare the effectiveness of rotary master apical file with ultrasonic activation of
      endodontic file in the removal of oil based intracanal medicament from the canal.

      Risk / Benefit Assessment At this point investigators are not anticipating any risk related
      to the trial intervention.

      TRIAL DESIGN: Two-arm parallel design, Randomized controlled trial. SETTING: Dental Clinics,
      Aga Khan University Hospital, Karachi

      EXPECTED DURATION OF TRIAL:

      Study Duration: Four months after registration By visit: 2 visits, with followup period of 7
      days±3 after the first visit.

      CRITERIA FOR EVALUATION Primary Efficacy Endpoint Reduction in microbial load (CFU/ml) at 7
      days after use of intracanal medicament Safety Evaluations No Incidence of adverse events
      with any agent

      Investigational product management: The investigator will purchase the drug locally and will
      label and store in safe and secure place. The product can be stored at room temperature
      i.e.1-30℃

      Sampling technique: Non probability purposive sampling Sampling size: Sample size was
      calculated using WHO sample size calculator. Dutta et al.16 showed that the population mean
      and SD of teeth treated with calcium hydroxide based intracanal medicaments were 50.3±13
      CFU/mL. Keeping the absolute precision at 0.05 and level of confidence at 95%, the required
      sample size turned out to be 26 teeth. The sample is inflated to 30. As tthere are two
      groups, therefore, a total of 60 teeth will be taken.

      RANDOMIZATION, BLINDING AND TREATMENT ALLOCATION:

      The selected subjects will be assigned to one of the two study groups only known to the
      researcher who is not involved in the outcome assessment using block randomization. This
      would be facilitated by CTU. The block size would be 6.

      Group A (Control group) - Calcipex group (n = 30) Group B (Intervention group) - Metapex
      group (n = 30) The sample in eppendorff tubes will be sent in a zip lock bag to the
      microbiology laboratory labeled with either group A or B. Patient, analyzer and the
      statistician will be blinded about the intervention groups. The recruitment of patients,
      collection of samples and placement of intracanal medicament will be performed by a single
      investigator.

      POSSIBLE RISKS OR BENEFITS:

      There is no risk involved in this study as the study is based on routine procedure of
      endodontic treatment. It will be a benefit for future patients which will help us to decide
      which intracanal medicament is more effective to use in infected canals.

      DATA COLLECTION INSTRUMENTS The data will be collected on case report form (CRF) on first and
      second visit. The CRF has been developed by investigator and reviewed by experts of the
      field. Data will be stored in a password protected database. To assure quality, data will be
      double checked to avoid discrepancies and errors.

      PATIENT CONFIDENTIALITY, ACCESS AND STORAGE:

      The information provided by the participant will remain confidential. Nobody except
      investigators will have access to it. Participants' name and identity will not be disclosed
      at any time. However, the data may be seen by ethical review committee, DSMB or any local
      regulatory body. As per GCP and other guidelines, data will be retained for 3 years.

      ETHICAL CONSIDERATIONS:

      The study will be started after obtaining approval from Institutional Ethics Review
      Committee(approved already). Patients who fulfilled the inclusion criteria will receive
      detailed information regarding the study and only those participants will be recruited who
      will sign the written consent form. The study will be conducted according to the World
      Medical Association's Declaration of Helsinki and the principles of GCP (Good Clinical
      Practice). Any subsequent protocol amendments will be submitted to ERC and regulatory
      authorities for approval. The trial will be conducted in compliance with regulations,
      particularly specifying pharmaco-vigilance reporting and a copy of final study report will be
      submitted to ERC.

      DATA COLLECTION PROCEDURE:

      First visit: The tooth diagnosed with chronic apical periodontitis will be anesthetized using
      2% lidocaine (with 1:100,000 epinephrine) and isolated with the rubber dam. Access opening
      will be performed using high and low speed round bur. Coronal and radicular necrotic pulp
      will be extirpated using barbed broaches. The root canal will be initially prepared by using
      hand K-files (Endoflex; K-File, Size 8-20, NiTi) with quarter turn and pull motion. A
      23-gauge side vented needle will be used to deliver 1 mL of sodium hypochlorite for
      irrigation after each instrument size. The working length will be established with an apex
      locator and confirmed by the periapical radiographs. Chemo-mechanical preparation will be
      completed using Protaper Next (Dentsply; Sirona, USA) depending on both root anatomy and
      initial diameter of the root canal. The preparation will be completed in the same appointment
      in all cases. After completion of the preparation, the canals will be irrigated with saline
      and dried with paper points. A sterile paper point (size 20; EZ Endo, USA) will be inserted
      to the confirmed working length of the canal, and retained in position for 60 seconds for
      sampling (S1). Afterwards, the paperpoint will be gently removed and placed in an eppendorf
      tube (5 ml) containing Brain Heart Infusion Broth and sent directly to the microbiology
      laboratory for microbial cultivation.

      In Group A, the canal will be medicated with Calcipex (Calcipex®II, Nishika, Yamaguchi,
      Japan) which will be placed by means of lentulo spiral fillers and packed with a cotton
      pellet at the level of canal entrance. Access cavity will be filled with a temporary filling,
      Cavit-G (3M-ESPE, USA). In Group B, the canal will be medicated with Metapex (Meta Biomed,
      Korea) using the same protocol as mentioned above.

      Second visit: Patient will be followed up on seven +/- 3 days, the tooth will be isolated and
      the protocol will be followed the same way as described before. The temporary filling will be
      removed and the paste carried out of the canal by using sterile file and irrigated with
      normal saline to wash out the medicament. A post medication sample will be taken with the
      help of sterile paper point in both groups as described previously (S2). The canals will be
      then obturated with gutta-percha and calcium hydroxide sealer (Sealapex, Kerr Dental, USA) by
      lateral compaction technique. A definitive restoration will be placed subsequently.

      Outcome assessment: It will be done in the microbiology laboratory on the basis of CFU/ml.

      RIGHT OF REFUSAL TO PARTICIPATE AND WITHDRAWAL:

      Participants will be given choice to either participate or refuse to participate in the study

      INCENTIVE:

      No incentive will be given to the patient.
    

Intervention name(s): Calcipex II; Metapex
Intervention type(s): Drug; Drug
Intervention description(s): Water based intracanal medicament; Oil based intracanal medicament
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: First visit: After chemomechanical preparation, irrigation and drying, a sterile paper point (size 20; EZ Endo, USA) will be inserted to the confirmed working length of the canal, and retained in position for 60 seconds for sampling (S1). Afterwards, the paperpoint will be gently removed and placed in an eppendorf tube (5 ml) containing Brain Heart Infusion Broth and sent directly to the microbiology laboratory for microbial cultivation. Respective intracanal medicament will be placed by means of lentulo spiral fillers and packed with a cotton pellet at the level of canal entrance. Access cavity will be filled with a temporary filling, Cavit-G. Second visit after 7 day, medicament will be removed. In case of Metapex (oil based medicament) either Protaper rotary or ultrasonic activation of file will be used for removal and radiograph obtained to ensure removal and sample will be obtained(S2). The canals will be then obturated. A definitive restoration will be placed subsequently.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: intracanal medicament; medicament removal; bacterial culture; efficacy; oil based medicament; colony forming unit