Effect of Irrigation With Antibiotic-containing Solutions on Postoperative Pain and Intra-canal Bacteria

• ClinicalTrials.gov Identifier: NCT04035070
• Recruitment Status: Not yet recruiting
• First Posted: July 29, 2019
• Last Update Posted: July 29, 2019
• Sponsor: Cairo University
• Information provided by (Responsible Party): Michel Karam Eissa Elias, Cairo University

Study Description

Brief Summary:

• The aim of this study is to compare the degree of postoperative pain and the antimicrobial effect in terms of bacterial count reduction after using co-amoxiclav-clindamycin solution versus MTAD and sodium hypochlorite irrigating solutions in patients with necrotic pulp.

Condition or disease	Intervention/treatment	Phase
Necrotic Pulp	Combination Product: co-amoxiclav-clindamycin solution; Combination Product: MTAD; Combination Product: 2.5% sodium hypochlorite	Phase 4

Detailed Description:

• After confirming the diagnosis and making sure that the patient conforms to all eligibility criteria, the principal investigator will enroll the patient in the study.

• The operator will complete treatment of all cases in two visits as follows:

  1. Anesthesia will be achieved using inferior alveolar nerve block for mandibular premolar teeth and infiltration technique for maxillary anterior teeth with local anesthesic solution of 1.8 mL of 2% Mepivacaine HCl with 1:100,000 epinephrine.
  2. Caries and/or coronal restorations will be completely removed with sterile bur and rubber dam will then be applied.
  3. The operative field, including the tooth, the clamp and rubber dam sheet will be cleaned with 30% hydrogen peroxide for 30 seconds, followed by a sterile cotton swab with 5.25% NaOCl for the same period of time and then inactivated with 5% sodium thiosulphate.
  4. Access cavity will be prepared using a sterile round carbide bur size 3 and a sterile Endo-Z bur.
  5. The operative field and the pulp chamber will be cleaned and disinfected once again in the same way mentioned above.
  6. Patency of the root canals will be achieved using #10 or #15 size stainless steel hand K-files. Working length (WL) will be determined using an electronic apex locator then confirmed radiographically to be 1 mm shorter than radiographic apex.
  7. Debridement and mechanical preparation will be performed with the initial file along with 2 mL of 0.9% sterile saline solution and then a pre-instrumentation sample will be collected from the root canal.

  8. The pre-instrumentation sample (S1) will be collected as follows: a sterile paper point will be placed inside the root canal to soak up the fluid in the canal to a level approximately 1 mm short of the tooth apex. The paper point will be left in the canal for 60 seconds. This will be repeated using three sterile paper points. Paper points will then be transferred aseptically to tubes containing 20 mL of sterile thioglycolate broth.

     Microbiological analysis To test for the presence of cultivable bacteria, cultures will be inoculated in thioglycolate broth. For the identification of main anaerobic taxa, the root canal samples will be plated on 5% sheep blood agar, neomycin blood agar and phenyl ethyl alcohol agar with metronidazole (5μg, Oxoid, Basingstoke, UK) disc. Cultures will be incubated at 37°C for 72 hours in an anaerobic chamber . In addition, specimens will also be cultured aerobically on 5% sheep blood agar and MacConkey's agar.

  9. Mechanical preparation will be completed in a crown down technique with Protaper Next rotary files set on an endodontic motor adjusted at a speed of 300 rpm and torque of 2 Ncm. In-and-out motions will be applied with stroke lengths not exceeding 3 mm in the cervical, middle, and apical thirds until attaining the established WL. All root canals will be enlarged to size X4 (40.06). The canal will be irrigated and recapitulated after the use of each instrument according to the allocated group as follows:

     Group 1: Alternate irrigation with 1 mL antibiotic-containing solution followed by 4 mL 2.5% sodium hypochlorite solution between each size instrument and the consequent one. The antibiotic-containing solution will be prepared by mixing equal quantities of 1.2 gm Co-amoxiclav solution and 600 mg Clindamycin solution at a ratio of 1:1 by volume.

     Group 2: Irrigation with 5 mL MTAD irrigating solution for 5 minutes between each size instrument and the consequent one.

     Group 3 (control): Irrigation with 5 mL 2.5% sodium hypochlorite irrigating solution between each size instrument and the consequent one.

  10. The root canal will be thoroughly irrigated with the allocated irrigant using a plastic disposable syringe with a gauge 30 side-vented needle reaching 1 mm short of the WL. The canal will then be dried using sterile paper points.
  11. Canals irrigated with NaOCl (groups 1 and 3) will be flushed with 5 mL of 5% sodium thiosulfate to inactivate the NaOCl followed by 5 mL 0.9% sterile saline solution. Canals irrigated with MTAD (group 2) will be flushed with 5 mL 0.9% sterile saline solution.
  12. A post-instrumentation sample (S2) will be taken as previously described and then the cavity will be sealed with a sterile cotton pellet and a temporary filling material .
  13. The patient will be instructed to record their pain level on NRS at 24 and 48 hours postoperatively and will be recalled after 72 hours. The patient will be prescribed Ibuprofen (400 mg) to be taken in case of intolerable pain.
  14. In the recall appointment, the root canal will be accessed under sterile conditions and will be flushed with 1mL sterile saline solution before a third sample (S3) is taken as previously described.
  15. Master cone fit radiograph will be taken and then the root canal will be dried using sterile paper points and filled with gutta percha points and resin-based sealer using cold lateral condensation technique.
  16. Access cavity will be sealed with a temporary filling material and the final restoration will be placed within one week.
  17. The patient will be asked to report any swelling, in such case, he/she will be appointed for clinical examination to assess the severity by a blinded assessor and to determine if systemic antibiotics/drainage will be needed.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Irrigation With Antibiotic-containing Solutions Versus Sodium Hypochlorite on Postoperative Pain and Intra-canal Bacteria in Teeth With Necrotic Pulps (a Randomized Double-blind Clinical Trial)
• Estimated Study Start Date: May 2020
• Estimated Primary Completion Date: January 2021
• Estimated Study Completion Date: May 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Root canal irrigation with co-amoxiclav-clindamycin solution; Alternate irrigation with 1 mL antibiotic-containing solution followed by 4 mL 2.5% sodium hypochlorite solution between each size instrument and the consequent one. The antibiotic-containing solution will be prepared by mixing equal quantities of 1.2 gm Co-amoxiclav solution and 600 mg Clindamycin solution at a ratio of 1:1 by volume.	Combination Product: co-amoxiclav-clindamycin solution; antibiotic-containing solution will be prepared by mixing equal quantities of 1.2gm Co-amoxiclav solution and 600mg Clindamycin solution at a ratio of 1:1 by volume to be used as a root canal irrigating solution
Experimental: Root canal irrigation with MTAD; Irrigation with 5 mL MTAD irrigating solution for 5 minutes between each size instrument and the consequent one.	Combination Product: MTAD; mixture of 3% doxycycline hyclate, 4.25% citric acid and detergent (Tween 80) to be used as a root canal irrigating solution; Other Name: BioPure MTAD
Active Comparator: Root canal irrigation with 2.5% sodium hypochlorite; Irrigation with 5 mL 2.5% sodium hypochlorite irrigating solution between each size instrument and the consequent one.	Combination Product: 2.5% sodium hypochlorite; It will be prepared by adding 10mL of sterile distilled water to 10mL of 5.25% sodium hypochlorite solution to be used as a root canal irrigating solution

Outcome Measures

Primary Outcome Measures :

1. postoperative pain: numerical rating scale [ Time Frame: up to 48 hours after the first visit ]
   intensity of pain by numerical rating scale from 0 to 10

Secondary Outcome Measures :

1. intra-canal bacterial count [ Time Frame: 72 hours after root canal preparation ]
   pre and post-instrumentation samples to count intra-canal bacteria (CFU/mL)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Maxillary/mandibular single-rooted permanent teeth:

  • Diagnosed clinically with pulp necrosis.
  • Absence of spontaneous pain.
  • Normal/slight widening in the periodontal membrane space (PMS).
• Patients' acceptance to participate in the trial.
• Patients who can understand numerical rating scale (NRS) and can sign the informed consent.

Exclusion Criteria:

• Medically compromised patients: Pain levels and healing following treatment would be compromised as these patients show higher incidence of pain and lower healing rate.
• Patients with known allergy to penicillin or penicillin derivatives.
• Pregnant females: Avoid radiation exposure, anesthesia, and medication.
• If analgesics or antibiotics have been administrated by the patient during the past 24 hours preoperatively: Might alter their pain perception.
• Patients reporting bruxism or clenching: Avoid further pressure on an already inflamed tooth inducing subsequent irritation and inflammation.
• Teeth that show association with acute periapical abscess and swelling: Need special treatment steps which could involve additional visits with incision and drainage. Also, it could influence initiation and progression of postoperative pain.
• Greater than grade I mobility or pocket depth greater than 5mm. Need special surgical and/or periodontal therapy.
• Non-restorable teeth.
• Immature teeth.
• Radiographic evidence of periapical radiolucency, external or internal root resorption, vertical root fracture, perforation or calcification.

Contacts and Locations

Contacts

Contact: Michel K Elias, M.Sc.; +2 0122 553 5090; michel.karam.5@gmail.com

Contact: Heba El-Asfouri, Ph.D.; +2 0100 527 6232; heba.elasfouri@dentistry.cu.edu.eg

Locations

Egypt

Endodontic Department - Faculty of Dentistry - Cairo University

Cairo, Egypt

Sponsors and Collaborators

Cairo University

Investigators

• Principal Investigator: Michel K Elias, M.Sc.; faculty of dentistry Cairo university
• Study Director: Maged M Negm, Ph.D.; faculty of dentistry Cairo university
• Study Chair: Heba El-Asfouri, Ph.D.; faculty of dentistry Cairo university

More Information

Publications:

Pak JG, White SN. Pain prevalence and severity before, during, and after root canal treatment: a systematic review. J Endod. 2011 Apr;37(4):429-38. doi: 10.1016/j.joen.2010.12.016. Review.

El Mubarak AH, Abu-bakr NH, Ibrahim YE. Postoperative pain in multiple-visit and single-visit root canal treatment. J Endod. 2010 Jan;36(1):36-9. doi: 10.1016/j.joen.2009.09.003.

Kovac J, Kovac D. Effect of irrigating solutions in endodontic therapy. Bratisl Lek Listy. 2011;112(7):410-5. Review.

Saleh IM, Ruyter IE, Haapasalo M, Ørstavik D. Survival of Enterococcus faecalis in infected dentinal tubules after root canal filling with different root canal sealers in vitro. Int Endod J. 2004 Mar;37(3):193-8.

Estrela C, Estrela CR, Barbin EL, Spanó JC, Marchesan MA, Pécora JD. Mechanism of action of sodium hypochlorite. Braz Dent J. 2002;13(2):113-7.

Siqueira JF Jr, Machado AG, Silveira RM, Lopes HP, de Uzeda M. Evaluation of the effectiveness of sodium hypochlorite used with three irrigation methods in the elimination of Enterococcus faecalis from the root canal, in vitro. Int Endod J. 1997 Jul;30(4):279-82.

Siqueira JF Jr, Rôças IN, Favieri A, Lima KC. Chemomechanical reduction of the bacterial population in the root canal after instrumentation and irrigation with 1%, 2.5%, and 5.25% sodium hypochlorite. J Endod. 2000 Jun;26(6):331-4.

McComb D, Smith DC. A preliminary scanning electron microscopic study of root canals after endodontic procedures. J Endod. 1975 Jul;1(7):238-42.

Grigoratos D, Knowles J, Ng YL, Gulabivala K. Effect of exposing dentine to sodium hypochlorite and calcium hydroxide on its flexural strength and elastic modulus. Int Endod J. 2001 Mar;34(2):113-9.

Sim TP, Knowles JC, Ng YL, Shelton J, Gulabivala K. Effect of sodium hypochlorite on mechanical properties of dentine and tooth surface strain. Int Endod J. 2001 Mar;34(2):120-32.

Mohammadi Z, Abbott PV. Antimicrobial substantivity of root canal irrigants and medicaments: a review. Aust Endod J. 2009 Dec;35(3):131-9. doi: 10.1111/j.1747-4477.2009.00164.x. Review.

Torabinejad M, Cho Y, Khademi AA, Bakland LK, Shabahang S. The effect of various concentrations of sodium hypochlorite on the ability of MTAD to remove the smear layer. J Endod. 2003 Apr;29(4):233-9. Erratum in: J Endod. 2003 Jun;29(6):424.

Shabahang S, Torabinejad M. Effect of MTAD on Enterococcus faecalis-contaminated root canals of extracted human teeth. J Endod. 2003 Sep;29(9):576-9.

Zhang W, Torabinejad M, Li Y. Evaluation of cytotoxicity of MTAD using the MTT-tetrazolium method. J Endod. 2003 Oct;29(10):654-7.

Machnick TK, Torabinejad M, Munoz CA, Shabahang S. Effect of MTAD on flexural strength and modulus of elasticity of dentin. J Endod. 2003 Nov;29(11):747-50.

Pinheiro ET, Gomes BP, Drucker DB, Zaia AA, Ferraz CC, Souza-Filho FJ. Antimicrobial susceptibility of Enterococcus faecalis isolated from canals of root filled teeth with periapical lesions. Int Endod J. 2004 Nov;37(11):756-63.

Misuriya A, Bhardwaj A, Bhardwaj A, Aggrawal S, Kumar PP, Gajjarepu S. A comparative antimicrobial analysis of various root canal irrigating solutions on endodontic pathogens: an in vitro study. J Contemp Dent Pract. 2014 Mar 1;15(2):153-60.

Shailaja S, Bhat SS, Hegde SK. Comparison between the antibacterial efficacies of three root canal irrigating solutions: antibiotic containing irrigant, Chlorhexidine and Chlorhexidine + Cetrimide. Oral Health Dent Manag. 2013 Dec;12(4):295-9.

Garlapati R, Venigalla BS, Surakanti JR, Thumu J, Chennamaneni KC, Kalluru RS. Comparison of the Antimicrobial Efficacy of Two Antibiotics Sparfloxacin and Augmentin as Experimental Root Canal Irrigating Solutions against Enterococcus faecalis - An Invitro Study. J Clin Diagn Res. 2016 Mar;10(3):ZC57-60. doi: 10.7860/JCDR/2016/17199.7470. Epub 2016 Mar 1.

Kamberi B, Bajrami D, Stavileci M, Omeragiq S, Dragidella F, Koçani F. The Antibacterial Efficacy of Biopure MTAD in Root Canal Contaminated with Enterococcus faecalis. ISRN Dent. 2012;2012:390526. Epub 2012 Aug 1.

Agrawal V, Rao MR, Dhingra K, Gopal VR, Mohapatra A, Mohapatra A. An in vitro comparison of antimicrobial effcacy of three root canal irrigants-BioPure MTAD, 2% chlorhexidine gluconate and 5.25% sodium hypochlorite as a final rinse against E. faecalis. J Contemp Dent Pract. 2013 Sep 1;14(5):842-7.

Mohammadi Z, Shalavi S, Giardino L, Palazzi F, Mashouf RY, Soltanian A. Antimicrobial effect of three new and two established root canal irrigation solutions. Gen Dent. 2012 Nov-Dec;60(6):534-7; quiz p.538-9.

Torabinejad M, Shabahang S, Bahjri K. Effect of MTAD on postoperative discomfort: a randomized clinical trial. J Endod. 2005 Mar;31(3):171-6.

Jain P, Yeluri R, Garg N, Mayall S, Rallan M, Gupta S, Pathivada L. A Comparative Evaluation of the Effectiveness of Three Different Irrigating Solution on Microorganisms in the Root Canal: An Invivo Study. J Clin Diagn Res. 2015 Dec;9(12):ZC39-42. doi: 10.7860/JCDR/2015/13133.6991. Epub 2015 Dec 1.

Tulsani SG, Chikkanarasaiah N, Bethur S. An in vivo comparison of antimicrobial efficacy of sodium hypochlorite and Biopure MTAD™ against enterococcus faecalis in primary teeth: A qPCR study. J Clin Pediatr Dent. 2014 Fall;39(1):30-4.

Siqueira JF Jr, Rôças IN, Favieri A, Machado AG, Gahyva SM, Oliveira JC, Abad EC. Incidence of postoperative pain after intracanal procedures based on an antimicrobial strategy. J Endod. 2002 Jun;28(6):457-60.

Almeida G, Marques E, De Martin AS, da Silveira Bueno CE, Nowakowski A, Cunha RS. Influence of irrigating solution on postoperative pain following single-visit endodontic treatment: randomized clinical trial. J Can Dent Assoc. 2012;78:c84.

• Responsible Party: Michel Karam Eissa Elias, Assistant lecturer at endodontic department - School of dentistry - New Giza University, Cairo University
• ClinicalTrials.gov Identifier: NCT04035070
• Other Study ID Numbers: CEBC-CU-2019-10-145
• First Posted: July 29, 2019
• Last Update Posted: July 29, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Michel Karam Eissa Elias, Cairo University:

antibiotic-containg solution; co-amoxiclav-clindamycin solution; MTAD; sodium hypochlorite; postoperative pain; antimicrobial efficacy; root canal irrigation

Additional relevant MeSH terms:

Dental Pulp Necrosis; Pain, Postoperative; Necrosis; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Signs and Symptoms; Dental Pulp Diseases; Tooth Diseases; Stomatognathic Diseases; Anti-Bacterial Agents; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Amoxicillin-Potassium Clavulanate Combination; Antibiotics, Antitubercular; Sodium Hypochlorite; Eusol; Pharmaceutical Solutions; Anti-Infective Agents; Antitubercular Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Disinfectants; beta-Lactamase Inhibitors