<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04465149</url>
  </required_header>
  <id_info>
    <org_study_id>SecondUNI-1</org_study_id>
    <nct_id>NCT04465149</nct_id>
  </id_info>
  <brief_title>Efficacy of Differents Anaesthetics in Mandibular Third Molar Germectomy</brief_title>
  <official_title>Comparative Study of the Anaesthetic Efficacy of 4% Articaine Versus 2% Mepivacaine in Mandibular Third Molar Germectomy Using Different Anaesthetic Techniques: a Split-mouth Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Campania &quot;Luigi Vanvitelli&quot;</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Campania &quot;Luigi Vanvitelli&quot;</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aim: To compare the clinical efficacy of local anaesthetics with articaine 4% or mepivacaine&#xD;
      2% (both with epinephrine 1:100.000) using different anaesthetic techniques to perform&#xD;
      germectomy of lower third molars and to assess patients' feelings and pain during surgery.&#xD;
&#xD;
      Methods: 50 patients (ranged 11-16 years) who required germectomy of mandibular third molars&#xD;
      were recruited. Each patient received local anaesthesia on one side with articaine inoculated&#xD;
      with plexus technique while on the other side with mepivacaine using inferior alveolar nerve&#xD;
      block technique. The patients' evaluation was performed on pre and intraoperative&#xD;
      tactile-pressure feelings and intraoperative pain with four levels on the analogic visual&#xD;
      scale (VAS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The surgical extraction of a tooth that exhibits at least a third of its root in formation,&#xD;
      with a periodontal ligament discernible on panoramic x-ray, is defined as germectomy. Early&#xD;
      germectomy is a usefull intervention to avoid problems caused by lower third molar retention&#xD;
      and impaction, and it is often required before or after orthodontic treatment. This surgical&#xD;
      technique would also allow to avoid complications, such as inferior alveolar and lingual&#xD;
      nerve damage.&#xD;
&#xD;
      The control of the patient's pain and anxiety by using local anaesthesia is essential in oral&#xD;
      surgery: these aspects become more important in adolescents, above all in the case of third&#xD;
      molar germectomy. Local anaesthetic (LA) injection is often the only painfull part of the&#xD;
      dental procedure, and the fear associated with this technique is the main reason that leads&#xD;
      patients to avoid dental treatment.&#xD;
&#xD;
      During the execution of dental surgical procedures, anaesthesia of the structures innervated&#xD;
      by the mandibular nerve is necessary, and many local anaesthetic techniques are described in&#xD;
      the literature. Generally, infiltration plexus technique is usually performed for maxillary&#xD;
      procedures while IANB is used for molar mandibular sites with 2% local anaesthetics. Failure&#xD;
      rates for IANB are high, sometimes reaching 80% for the lower incisors with this technique,&#xD;
      and numerous approaches for the implementation of a new technique of IANB have been&#xD;
      described. Among them, the articaine 4% already has been successfully used to achieve local&#xD;
      anesthesia and facial infiltration anaesthetic technique in the mandible showed efficacy with&#xD;
      encouraging result that can be overlapped to the IANB technique. Articaine&#xD;
      (4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester&#xD;
      hydrochloride) contains a thiophene ring instead of benzene and an ester group. The thiophene&#xD;
      ring allows for higher lipid solubility so a greater portion of an administered dose can&#xD;
      enter in neurons. Gazal found that a combination of nerve block anaesthesia, buccal&#xD;
      infiltration and intra-ligamentary injection resulted in more profound anaesthesia (P =0.003)&#xD;
      and higher success rates compared to IANB alone in mandibular first molar pulp anaesthesia.&#xD;
      Other studies reported the use of articaine in implantology interventions in which it was&#xD;
      used with subperiosteal technique on the buccal and vestibular sides.&#xD;
&#xD;
      Thus, the literature showed several conflicting results on the mandibular facial plexus&#xD;
      infiltration technique used with different anesthetics.&#xD;
&#xD;
      Recent studies of this anaesthetic technique found that 1.8 cc of 4% articaine facial&#xD;
      infiltration in the mandible can be effective when the thickness of mandibular facial cortex&#xD;
      is &lt; 2.0-3.0 mm, with 5-10 minutes needed for the adequate anaesthesia.&#xD;
&#xD;
      It was reported that many dental procedures on deciduous molars could be accomplished with&#xD;
      infiltration of articaine alone in the pediatric population.&#xD;
&#xD;
      As above mentioned, the difficulty in achieving reliable anaesthesia in the third mandibular&#xD;
      molars in adults with facial infiltration of local anaesthetic is related to the thickness of&#xD;
      the cortical bone and inability to achieve consistently inferior alveolar nerve.&#xD;
&#xD;
      An ideal local anaesthetic should have the following characteristics:&#xD;
&#xD;
        1. short latency time;&#xD;
&#xD;
        2. strength of the intense effect;&#xD;
&#xD;
        3. duration of prolonged action;&#xD;
&#xD;
        4. lack of harmful local and systemic effects. Currently, mepivacaine is among the most&#xD;
           used and studied anaesthetics in dentistry; however, articaine is nowadays increasingly&#xD;
           used for its manageability, lack of side effects and high anaesthetic potency.&#xD;
           Mepivacaine is an amide-type anaesthetic with fast action from the beginning and 30-120&#xD;
           minutes duration. Its maximum allowed dose is 300 mg with epinephrine or 500 mg alone.&#xD;
           The dose for children is 4-6 mg/kg/dose (maximum: 270 mg) without epinephrine.&#xD;
&#xD;
      Articaine, due to its chemical characteristics, is quickly soluble and rapidly released from&#xD;
      adipose/lipid tissue. The ester side chain of articaine is hydrolyzed by plasmaesterases&#xD;
      rendering the molecule inactive. Evidence suggests that it is the local anaesthetic that best&#xD;
      spreads within soft and hard tissues. Then, it has a non-conducive effect on extended&#xD;
      operations having a shorter half-life of 25 minutes compared to approximately 90 minutes of&#xD;
      other amides (115 minutes for mepivacaine) that require hepatic clearance. Accordingly, it&#xD;
      was suggested that articaine does not own any relevant side effects or systemic toxicities.&#xD;
&#xD;
      For this reason, articaine has been used at higher concentrations (4%), associated with&#xD;
      epinephrine, compared to other local dental anesthetics. This higher concentration ensures an&#xD;
      excellent spread both in hard and soft tissues, also promoted by a pKa very similar to the&#xD;
      physiological pH of tissues. Its great liposolubility allows a rapid diffusion in adipose&#xD;
      tissue (spread coefficient = 17,0) and involves a lower adherence to the nerve membranes and,&#xD;
      above all, lower toxicity for the tissues. Moreover, articaine has a high protein-based bond&#xD;
      (94%) which allows a better affinity for the protein-based membrane receptors, and it is a&#xD;
      direct sign of its increased anaesthetic potency.&#xD;
&#xD;
      Dental local anaesthetics are often combined with vasoconstrictors, such as epinephrine, to&#xD;
      increase the depth and duration of analgesia. Clinical experiments, in which articaine&#xD;
      without vasoconstrictor was used, did not show any satisfying results, whereas the use of&#xD;
      articaine combined with low concentrations of vasoconstrictors produced better anaesthetic&#xD;
      effects than other common local anaesthetics such as bupivacaine and mepivacaine. It is well&#xD;
      documented that vasoconstrictors have a safety range if used at low doses, and not directly&#xD;
      injected in the blood vessels, even in particular care patients.&#xD;
&#xD;
      The present study aimed to compare the clinical efficacy of articaine 4% (epinephrine&#xD;
      1:100.000) versus mepivacaine 2% (epinephrine 1:100.000) for the surgical germectomy of&#xD;
      mandibular third molars with two different conventional anaesthetic techniques in young&#xD;
      patients whom jawbone is not completely mineralized yet and more penetrable by the articaine&#xD;
      molecule.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 30, 2018</start_date>
  <completion_date type="Actual">April 20, 2020</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The subjects were children undergoing orthodontic treatment in whom early extraction was indicated to facilitate their treatment in some specific conditions (i.e. posterior crowding, altered second molar eruption, non-extraction approach). For each subject, the first germectomy was scheduled 15 days apart. The same senior operator, assisted by the same practitioner, completed all the surgical procedures. All interventions made with mepivacaine were performed with the same anaesthetic technique routinely used in Oral surgery (IANB). The technique was complemented with anaesthesia of the buccal nerve, as routine for this technique, administering another 1.8 ml of the same anaesthetic used in each intervention. On the other hand, the surgical procedures in articaine cases were made practising a plexus technique, performing a deep buccal injection distally to the second mandibular molar.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Discomfort/Pain felt for anesthetic injection valued by the Patient on a Visual Analogue Scale</measure>
    <time_frame>At the beginning of Surgery</time_frame>
    <description>Once performed the injections, patients were asked to notice on a visual analogue scale, how much discomfort they felt due to the anaesthetic injections, indicating one of the following values:&#xD;
0 absent&#xD;
mild&#xD;
moderate&#xD;
severe</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Test during the Surgery</measure>
    <time_frame>After 10/15 minutes</time_frame>
    <description>The same test was repeated intraoperatively</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Local Anesthetic Efficacy</condition>
  <arm_group>
    <arm_group_label>Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who required germectomy of mandibular third molars. Each patient received local anaesthesia on one side with articaine inoculated with plexus technique while on the other side with mepivacaine using inferior alveolar nerve block technique.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Third Molar Germectomy</intervention_name>
    <description>Surgical extraction of Third Molars that exhibits at least a third of its root in formation, with a periodontal ligament discernible on panoramic x-ray (defined as germectomy).</description>
    <arm_group_label>Patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients requiring bilateral germectomy of mandibular third molars before orthodontic&#xD;
             treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients presenting systemic and oral diseases&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>11 Years</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marco Menditti, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Campania &quot;Luigi Vanvitelli&quot;</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Campania Luigi Vanvitelli</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Perillo L, Vitale M, d'Apuzzo F, Isola G, Nucera R, Matarese G. Interdisciplinary approach for a patient with unilateral cleft lip and palate. Am J Orthod Dentofacial Orthop. 2018 Jun;153(6):883-894. doi: 10.1016/j.ajodo.2016.12.035.</citation>
    <PMID>29853246</PMID>
  </results_reference>
  <results_reference>
    <citation>Raucci G, Pacheco-Pereira C, Elyasi M, d'Apuzzo F, Flores-Mir C, Perillo L. Short- and long-term evaluation of mandibular dental arch dimensional changes in patients treated with a lip bumper during mixed dentition followed by fixed appliances. Angle Orthod. 2016 Sep;86(5):753-60. doi: 10.2319/073015-519.1. Epub 2016 Jan 15.</citation>
    <PMID>26771718</PMID>
  </results_reference>
  <results_reference>
    <citation>Chiapasco M, Crescentini M, Romanoni G. [The extraction of the lower third molars: germectomy or late avulsion?]. Minerva Stomatol. 1994 May;43(5):191-8. Italian.</citation>
    <PMID>8072466</PMID>
  </results_reference>
  <results_reference>
    <citation>Rayati F, Noruziha A, Jabbarian R. Efficacy of buccal infiltration anaesthesia with articaine for extraction of mandibular molars: a clinical trial. Br J Oral Maxillofac Surg. 2018 Sep;56(7):607-610. doi: 10.1016/j.bjoms.2018.06.012. Epub 2018 Jul 3.</citation>
    <PMID>29980352</PMID>
  </results_reference>
  <results_reference>
    <citation>Almpani K, Kolokitha OE. Role of third molars in orthodontics. World J Clin Cases. 2015 Feb 16;3(2):132-40. doi: 10.12998/wjcc.v3.i2.132.</citation>
    <PMID>25685759</PMID>
  </results_reference>
  <results_reference>
    <citation>Bjornland T, Haanaes HR, Lind PO, Zachrisson B. Removal of third molar germs. Study of complications. Int J Oral Maxillofac Surg. 1987 Aug;16(4):385-90. doi: 10.1016/s0901-5027(87)80072-3.</citation>
    <PMID>3117908</PMID>
  </results_reference>
  <results_reference>
    <citation>Eccleston C. Role of psychology in pain management. Br J Anaesth. 2001 Jul;87(1):144-52. doi: 10.1093/bja/87.1.144.</citation>
    <PMID>11460803</PMID>
  </results_reference>
  <results_reference>
    <citation>Gunter JB. Benefit and risks of local anesthetics in infants and children. Paediatr Drugs. 2002;4(10):649-72. doi: 10.2165/00128072-200204100-00003.</citation>
    <PMID>12269841</PMID>
  </results_reference>
  <results_reference>
    <citation>Milgrom P, Coldwell SE, Getz T, Weinstein P, Ramsay DS. Four dimensions of fear of dental injections. J Am Dent Assoc. 1997 Jun;128(6):756-66. doi: 10.14219/jada.archive.1997.0301.</citation>
    <PMID>9188235</PMID>
  </results_reference>
  <results_reference>
    <citation>Kaufman E, Epstein JB, Naveh E, Gorsky M, Gross A, Cohen G. A survey of pain, pressure, and discomfort induced by commonly used oral local anesthesia injections. Anesth Prog. 2005 Winter;52(4):122-7. doi: 10.2344/0003-3006(2005)52[122:ASP]2.0.CO;2.</citation>
    <PMID>16596910</PMID>
  </results_reference>
  <results_reference>
    <citation>Khoury J, Townsend G. Neural blockade anaesthesia of the mandibular nerve and its terminal branches: rationale for different anaesthetic techniques including their advantages and disadvantages. Anesthesiol Res Pract. 2011;2011:307423. doi: 10.1155/2011/307423. Epub 2011 May 25.</citation>
    <PMID>21716730</PMID>
  </results_reference>
  <results_reference>
    <citation>Flanagan DF. The effectiveness of articaine in mandibular facial infiltrations. Local Reg Anesth. 2015 Dec 18;9:1-6. doi: 10.2147/LRA.S94647. eCollection 2016.</citation>
    <PMID>26730209</PMID>
  </results_reference>
  <results_reference>
    <citation>Saxena P, Gupta SK, Newaskar V, Chandra A. Advances in dental local anesthesia techniques and devices: An update. Natl J Maxillofac Surg. 2013 Jan;4(1):19-24. doi: 10.4103/0975-5950.117873.</citation>
    <PMID>24163548</PMID>
  </results_reference>
  <results_reference>
    <citation>Meechan JG. The use of the mandibular infiltration anesthetic technique in adults. J Am Dent Assoc. 2011 Sep;142 Suppl 3:19S-24S. doi: 10.14219/jada.archive.2011.0343.</citation>
    <PMID>21881058</PMID>
  </results_reference>
  <results_reference>
    <citation>Malamed SF. Is the mandibular nerve block passe? J Am Dent Assoc. 2011 Sep;142 Suppl 3:3S-7S. doi: 10.14219/jada.archive.2011.0340.</citation>
    <PMID>21881055</PMID>
  </results_reference>
  <results_reference>
    <citation>Gazal G, Fareed WM, Zafar MS. Role of intraseptal anesthesia for pain-free dental treatment. Saudi J Anaesth. 2016 Jan-Mar;10(1):81-6. doi: 10.4103/1658-354X.169482.</citation>
    <PMID>26955316</PMID>
  </results_reference>
  <results_reference>
    <citation>Heller AA, Shankland WE 2nd. Alternative to the inferior alveolar nerve block anesthesia when placing mandibular dental implants posterior to the mental foramen. J Oral Implantol. 2001;27(3):127-33. doi: 10.1563/1548-1336(2001)0272.3.CO;2.</citation>
    <PMID>12500871</PMID>
  </results_reference>
  <results_reference>
    <citation>Leith R, Lynch K, O'Connell AC. Articaine use in children: a review. Eur Arch Paediatr Dent. 2012 Dec;13(6):293-6. doi: 10.1007/BF03320829.</citation>
    <PMID>23235128</PMID>
  </results_reference>
  <results_reference>
    <citation>Gazal G. Comparison of speed of action and injection discomfort of 4% articaine and 2% mepivacaine for pulpal anesthesia in mandibular teeth: A randomized, double-blind cross-over trial. Eur J Dent. 2015 Apr-Jun;9(2):201-206. doi: 10.4103/1305-7456.156811.</citation>
    <PMID>26038650</PMID>
  </results_reference>
  <results_reference>
    <citation>Cowan A. Clinical assessment of a new local anesthetic agent-carticaine. Oral Surg Oral Med Oral Pathol. 1977 Feb;43(2):174-80. doi: 10.1016/0030-4220(77)90153-0.</citation>
    <PMID>264643</PMID>
  </results_reference>
  <results_reference>
    <citation>Srisurang S, Narit L, Prisana P. Clinical efficacy of lidocaine, mepivacaine, and articaine for local infiltration. J Investig Clin Dent. 2011 Feb;2(1):23-8. doi: 10.1111/j.2041-1626.2010.00035.x. Epub 2010 Nov 8.</citation>
    <PMID>25427324</PMID>
  </results_reference>
  <results_reference>
    <citation>Vree TB, Gielen MJ. Clinical pharmacology and the use of articaine for local and regional anaesthesia. Best Pract Res Clin Anaesthesiol. 2005 Jun;19(2):293-308. doi: 10.1016/j.bpa.2004.12.006.</citation>
    <PMID>15966499</PMID>
  </results_reference>
  <results_reference>
    <citation>Jastak JT, Yagiela JA. Vasoconstrictors and local anesthesia: a review and rationale for use. J Am Dent Assoc. 1983 Oct;107(4):623-30. doi: 10.14219/jada.archive.1983.0307. No abstract available.</citation>
    <PMID>6355236</PMID>
  </results_reference>
  <results_reference>
    <citation>Leuschner J, Leblanc D. Studies on the toxicological profile of the local anaesthetic articaine. Arzneimittelforschung. 1999 Feb;49(2):126-32. doi: 10.1055/s-0031-1300372.</citation>
    <PMID>10083981</PMID>
  </results_reference>
  <results_reference>
    <citation>Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A Comparison of Different Volumes of Articaine for Inferior Alveolar Nerve Block for Molar Teeth with Symptomatic Irreversible Pulpitis. J Endod. 2015 Sep;41(9):1408-11. doi: 10.1016/j.joen.2015.05.015. Epub 2015 Jul 3.</citation>
    <PMID>26149210</PMID>
  </results_reference>
  <results_reference>
    <citation>Mittal M, Sharma S, Kumar A, Chopra R, Srivastava D. Comparison of Anesthetic Efficacy of Articaine and Lidocaine During Primary Maxillary Molar Extractions in Children. Pediatr Dent. 2015 Nov-Dec;37(7):520-4.</citation>
    <PMID>26883609</PMID>
  </results_reference>
  <results_reference>
    <citation>Corbett IP, Kanaa MD, Whitworth JM, Meechan JG. Articaine infiltration for anesthesia of mandibular first molars. J Endod. 2008 May;34(5):514-8. doi: 10.1016/j.joen.2008.02.042.</citation>
    <PMID>18436027</PMID>
  </results_reference>
  <results_reference>
    <citation>Pellicer-Chover H, Cervera-Ballester J, Sanchis-Bielsa JM, Penarrocha-Diago MA, Penarrocha-Diago M, Garcia-Mira B. Comparative split-mouth study of the anesthetic efficacy of 4% articaine versus 0.5% bupivacaine in impacted mandibular third molar extraction. J Clin Exp Dent. 2013 Apr 1;5(2):e66-71. doi: 10.4317/jced.50869. eCollection 2013 Apr 1.</citation>
    <PMID>24455059</PMID>
  </results_reference>
  <results_reference>
    <citation>Ram D, Peretz B. Administering local anaesthesia to paediatric dental patients -- current status and prospects for the future. Int J Paediatr Dent. 2002 Mar;12(2):80-9. doi: 10.1046/j.1365-263x.2002.00343.x.</citation>
    <PMID>11966886</PMID>
  </results_reference>
  <results_reference>
    <citation>Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth Prog. 2012 Summer;59(2):90-101; quiz 102-3. doi: 10.2344/0003-3006-59.2.90.</citation>
    <PMID>22822998</PMID>
  </results_reference>
  <results_reference>
    <citation>Vigen EC, Lasse A. Articaine hydrochloride: is it the solution? Dent Update. 2015 Jun;42(5):493. doi: 10.12968/denu.2015.42.5.493. No abstract available.</citation>
    <PMID>26964452</PMID>
  </results_reference>
  <results_reference>
    <citation>Kammerer PW, Palarie V, Daublander M, Bicer C, Shabazfar N, Brullmann D, Al-Nawas B. Comparison of 4% articaine with epinephrine (1:100,000) and without epinephrine in inferior alveolar block for tooth extraction: double-blind randomized clinical trial of anesthetic efficacy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Apr;113(4):495-9. doi: 10.1016/j.tripleo.2011.04.037. Epub 2011 Aug 6.</citation>
    <PMID>22676931</PMID>
  </results_reference>
  <results_reference>
    <citation>Pabst L, Nusstein J, Drum M, Reader A, Beck M. The efficacy of a repeated buccal infiltration of articaine in prolonging duration of pulpal anesthesia in the mandibular first molar. Anesth Prog. 2009 Winter;56(4):128-34. doi: 10.2344/0003-3006-56.4.128.</citation>
    <PMID>20020793</PMID>
  </results_reference>
  <results_reference>
    <citation>Dudkiewicz A, Schwartz S, Laliberte R. Effectiveness of mandibular infiltration in children using the local anesthetic Ultracaine (articaine hydrochloride). J Can Dent Assoc. 1987 Jan;53(1):29-31. No abstract available.</citation>
    <PMID>3545399</PMID>
  </results_reference>
  <results_reference>
    <citation>Tofoli GR, Ramacciato JC, de Oliveira PC, Volpato MC, Groppo FC, Ranali J. Comparison of effectiveness of 4% articaine associated with 1: 100,000 or 1: 200,000 epinephrine in inferior alveolar nerve block. Anesth Prog. 2003;50(4):164-8.</citation>
    <PMID>14959904</PMID>
  </results_reference>
  <results_reference>
    <citation>Sierra Rebolledo A, Delgado Molina E, Berini Aytis L, Gay Escoda C. Comparative study of the anesthetic efficacy of 4% articaine versus 2% lidocaine in inferior alveolar nerve block during surgical extraction of impacted lower third molars. Med Oral Patol Oral Cir Bucal. 2007 Mar 1;12(2):E139-44.</citation>
    <PMID>17322803</PMID>
  </results_reference>
  <results_reference>
    <citation>Wright GZ, Weinberger SJ, Marti R, Plotzke O. The effectiveness of infiltration anesthesia in the mandibular primary molar region. Pediatr Dent. 1991 Sep-Oct;13(5):278-83.</citation>
    <PMID>1815200</PMID>
  </results_reference>
  <results_reference>
    <citation>Ramadurai N, Gurunathan D, Samuel AV, Subramanian E, Rodrigues SJL. Effectiveness of 2% Articaine as an anesthetic agent in children: randomized controlled trial. Clin Oral Investig. 2019 Sep;23(9):3543-3550. doi: 10.1007/s00784-018-2775-5. Epub 2018 Dec 14.</citation>
    <PMID>30552590</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>May 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Campania &quot;Luigi Vanvitelli&quot;</investigator_affiliation>
    <investigator_full_name>Alfredo De Rosa</investigator_full_name>
    <investigator_title>Associated Professor</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 20, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/49/NCT04465149/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04465149
org study id: SecondUNI-1
nct id: NCT04465149
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Aim: To compare the clinical efficacy of local anaesthetics with articaine 4% or mepivacaine
      2% (both with epinephrine 1:100.000) using different anaesthetic techniques to perform
      germectomy of lower third molars and to assess patients' feelings and pain during surgery.

      Methods: 50 patients (ranged 11-16 years) who required germectomy of mandibular third molars
      were recruited. Each patient received local anaesthesia on one side with articaine inoculated
      with plexus technique while on the other side with mepivacaine using inferior alveolar nerve
      block technique. The patients' evaluation was performed on pre and intraoperative
      tactile-pressure feelings and intraoperative pain with four levels on the analogic visual
      scale (VAS).
The surgical extraction of a tooth that exhibits at least a third of its root in formation,
      with a periodontal ligament discernible on panoramic x-ray, is defined as germectomy. Early
      germectomy is a usefull intervention to avoid problems caused by lower third molar retention
      and impaction, and it is often required before or after orthodontic treatment. This surgical
      technique would also allow to avoid complications, such as inferior alveolar and lingual
      nerve damage.

      The control of the patient's pain and anxiety by using local anaesthesia is essential in oral
      surgery: these aspects become more important in adolescents, above all in the case of third
      molar germectomy. Local anaesthetic (LA) injection is often the only painfull part of the
      dental procedure, and the fear associated with this technique is the main reason that leads
      patients to avoid dental treatment.

      During the execution of dental surgical procedures, anaesthesia of the structures innervated
      by the mandibular nerve is necessary, and many local anaesthetic techniques are described in
      the literature. Generally, infiltration plexus technique is usually performed for maxillary
      procedures while IANB is used for molar mandibular sites with 2% local anaesthetics. Failure
      rates for IANB are high, sometimes reaching 80% for the lower incisors with this technique,
      and numerous approaches for the implementation of a new technique of IANB have been
      described. Among them, the articaine 4% already has been successfully used to achieve local
      anesthesia and facial infiltration anaesthetic technique in the mandible showed efficacy with
      encouraging result that can be overlapped to the IANB technique. Articaine
      (4-methyl-3-[2-(propylamino)-propionamido]-2-thiophene-carboxylic acid, methyl ester
      hydrochloride) contains a thiophene ring instead of benzene and an ester group. The thiophene
      ring allows for higher lipid solubility so a greater portion of an administered dose can
      enter in neurons. Gazal found that a combination of nerve block anaesthesia, buccal
      infiltration and intra-ligamentary injection resulted in more profound anaesthesia (P =0.003)
      and higher success rates compared to IANB alone in mandibular first molar pulp anaesthesia.
      Other studies reported the use of articaine in implantology interventions in which it was
      used with subperiosteal technique on the buccal and vestibular sides.

      Thus, the literature showed several conflicting results on the mandibular facial plexus
      infiltration technique used with different anesthetics.

      Recent studies of this anaesthetic technique found that 1.8 cc of 4% articaine facial
      infiltration in the mandible can be effective when the thickness of mandibular facial cortex
      is < 2.0-3.0 mm, with 5-10 minutes needed for the adequate anaesthesia.

      It was reported that many dental procedures on deciduous molars could be accomplished with
      infiltration of articaine alone in the pediatric population.

      As above mentioned, the difficulty in achieving reliable anaesthesia in the third mandibular
      molars in adults with facial infiltration of local anaesthetic is related to the thickness of
      the cortical bone and inability to achieve consistently inferior alveolar nerve.

      An ideal local anaesthetic should have the following characteristics:

        1. short latency time;

        2. strength of the intense effect;

        3. duration of prolonged action;

        4. lack of harmful local and systemic effects. Currently, mepivacaine is among the most
           used and studied anaesthetics in dentistry; however, articaine is nowadays increasingly
           used for its manageability, lack of side effects and high anaesthetic potency.
           Mepivacaine is an amide-type anaesthetic with fast action from the beginning and 30-120
           minutes duration. Its maximum allowed dose is 300 mg with epinephrine or 500 mg alone.
           The dose for children is 4-6 mg/kg/dose (maximum: 270 mg) without epinephrine.

      Articaine, due to its chemical characteristics, is quickly soluble and rapidly released from
      adipose/lipid tissue. The ester side chain of articaine is hydrolyzed by plasmaesterases
      rendering the molecule inactive. Evidence suggests that it is the local anaesthetic that best
      spreads within soft and hard tissues. Then, it has a non-conducive effect on extended
      operations having a shorter half-life of 25 minutes compared to approximately 90 minutes of
      other amides (115 minutes for mepivacaine) that require hepatic clearance. Accordingly, it
      was suggested that articaine does not own any relevant side effects or systemic toxicities.

      For this reason, articaine has been used at higher concentrations (4%), associated with
      epinephrine, compared to other local dental anesthetics. This higher concentration ensures an
      excellent spread both in hard and soft tissues, also promoted by a pKa very similar to the
      physiological pH of tissues. Its great liposolubility allows a rapid diffusion in adipose
      tissue (spread coefficient = 17,0) and involves a lower adherence to the nerve membranes and,
      above all, lower toxicity for the tissues. Moreover, articaine has a high protein-based bond
      (94%) which allows a better affinity for the protein-based membrane receptors, and it is a
      direct sign of its increased anaesthetic potency.

      Dental local anaesthetics are often combined with vasoconstrictors, such as epinephrine, to
      increase the depth and duration of analgesia. Clinical experiments, in which articaine
      without vasoconstrictor was used, did not show any satisfying results, whereas the use of
      articaine combined with low concentrations of vasoconstrictors produced better anaesthetic
      effects than other common local anaesthetics such as bupivacaine and mepivacaine. It is well
      documented that vasoconstrictors have a safety range if used at low doses, and not directly
      injected in the blood vessels, even in particular care patients.

      The present study aimed to compare the clinical efficacy of articaine 4% (epinephrine
      1:100.000) versus mepivacaine 2% (epinephrine 1:100.000) for the surgical germectomy of
      mandibular third molars with two different conventional anaesthetic techniques in young
      patients whom jawbone is not completely mineralized yet and more penetrable by the articaine
      molecule.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The subjects were children undergoing orthodontic treatment in whom early extraction was indicated to facilitate their treatment in some specific conditions (i.e. posterior crowding, altered second molar eruption, non-extraction approach). For each subject, the first germectomy was scheduled 15 days apart. The same senior operator, assisted by the same practitioner, completed all the surgical procedures. All interventions made with mepivacaine were performed with the same anaesthetic technique routinely used in Oral surgery (IANB). The technique was complemented with anaesthesia of the buccal nerve, as routine for this technique, administering another 1.8 ml of the same anaesthetic used in each intervention. On the other hand, the surgical procedures in articaine cases were made practising a plexus technique, performing a deep buccal injection distally to the second mandibular molar.
primary purpose: Supportive Care
masking: None (Open Label)
measure: Discomfort/Pain felt for anesthetic injection valued by the Patient on a Visual Analogue Scale
time frame: At the beginning of Surgery
description: Once performed the injections, patients were asked to notice on a visual analogue scale, how much discomfort they felt due to the anaesthetic injections, indicating one of the following values:
0 absent
mild
moderate
severe
measure: Test during the Surgery
time frame: After 10/15 minutes
description: The same test was repeated intraoperatively
arm group label: Patients
arm group type: Experimental
description: Patients who required germectomy of mandibular third molars. Each patient received local anaesthesia on one side with articaine inoculated with plexus technique while on the other side with mepivacaine using inferior alveolar nerve block technique.
intervention type: Procedure
intervention name: Third Molar Germectomy
description: Surgical extraction of Third Molars that exhibits at least a third of its root in formation, with a periodontal ligament discernible on panoramic x-ray (defined as germectomy).
arm group label: Patients
criteria: 
gender: All
minimum age: 11 Years
maximum age: 16 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marco Menditti, Doctor
role: Principal Investigator
affiliation: University of Campania "Luigi Vanvitelli"
facility: 
country: Italy
citation: Perillo L, Vitale M, d'Apuzzo F, Isola G, Nucera R, Matarese G. Interdisciplinary approach for a patient with unilateral cleft lip and palate. Am J Orthod Dentofacial Orthop. 2018 Jun;153(6):883-894. doi: 10.1016/j.ajodo.2016.12.035.
PMID: 29853246
citation: Raucci G, Pacheco-Pereira C, Elyasi M, d'Apuzzo F, Flores-Mir C, Perillo L. Short- and long-term evaluation of mandibular dental arch dimensional changes in patients treated with a lip bumper during mixed dentition followed by fixed appliances. Angle Orthod. 2016 Sep;86(5):753-60. doi: 10.2319/073015-519.1. Epub 2016 Jan 15.
PMID: 26771718
citation: Chiapasco M, Crescentini M, Romanoni G. [The extraction of the lower third molars: germectomy or late avulsion?]. Minerva Stomatol. 1994 May;43(5):191-8. Italian.
PMID: 8072466
citation: Rayati F, Noruziha A, Jabbarian R. Efficacy of buccal infiltration anaesthesia with articaine for extraction of mandibular molars: a clinical trial. Br J Oral Maxillofac Surg. 2018 Sep;56(7):607-610. doi: 10.1016/j.bjoms.2018.06.012. Epub 2018 Jul 3.
PMID: 29980352
citation: Almpani K, Kolokitha OE. Role of third molars in orthodontics. World J Clin Cases. 2015 Feb 16;3(2):132-40. doi: 10.12998/wjcc.v3.i2.132.
PMID: 25685759
citation: Bjornland T, Haanaes HR, Lind PO, Zachrisson B. Removal of third molar germs. Study of complications. Int J Oral Maxillofac Surg. 1987 Aug;16(4):385-90. doi: 10.1016/s0901-5027(87)80072-3.
PMID: 3117908
citation: Eccleston C. Role of psychology in pain management. Br J Anaesth. 2001 Jul;87(1):144-52. doi: 10.1093/bja/87.1.144.
PMID: 11460803
citation: Gunter JB. Benefit and risks of local anesthetics in infants and children. Paediatr Drugs. 2002;4(10):649-72. doi: 10.2165/00128072-200204100-00003.
PMID: 12269841
citation: Milgrom P, Coldwell SE, Getz T, Weinstein P, Ramsay DS. Four dimensions of fear of dental injections. J Am Dent Assoc. 1997 Jun;128(6):756-66. doi: 10.14219/jada.archive.1997.0301.
PMID: 9188235
citation: Kaufman E, Epstein JB, Naveh E, Gorsky M, Gross A, Cohen G. A survey of pain, pressure, and discomfort induced by commonly used oral local anesthesia injections. Anesth Prog. 2005 Winter;52(4):122-7. doi: 10.2344/0003-3006(2005)52[122:ASP]2.0.CO;2.
PMID: 16596910
citation: Khoury J, Townsend G. Neural blockade anaesthesia of the mandibular nerve and its terminal branches: rationale for different anaesthetic techniques including their advantages and disadvantages. Anesthesiol Res Pract. 2011;2011:307423. doi: 10.1155/2011/307423. Epub 2011 May 25.
PMID: 21716730
citation: Flanagan DF. The effectiveness of articaine in mandibular facial infiltrations. Local Reg Anesth. 2015 Dec 18;9:1-6. doi: 10.2147/LRA.S94647. eCollection 2016.
PMID: 26730209
citation: Saxena P, Gupta SK, Newaskar V, Chandra A. Advances in dental local anesthesia techniques and devices: An update. Natl J Maxillofac Surg. 2013 Jan;4(1):19-24. doi: 10.4103/0975-5950.117873.
PMID: 24163548
citation: Meechan JG. The use of the mandibular infiltration anesthetic technique in adults. J Am Dent Assoc. 2011 Sep;142 Suppl 3:19S-24S. doi: 10.14219/jada.archive.2011.0343.
PMID: 21881058
citation: Malamed SF. Is the mandibular nerve block passe? J Am Dent Assoc. 2011 Sep;142 Suppl 3:3S-7S. doi: 10.14219/jada.archive.2011.0340.
PMID: 21881055
citation: Gazal G, Fareed WM, Zafar MS. Role of intraseptal anesthesia for pain-free dental treatment. Saudi J Anaesth. 2016 Jan-Mar;10(1):81-6. doi: 10.4103/1658-354X.169482.
PMID: 26955316
citation: Heller AA, Shankland WE 2nd. Alternative to the inferior alveolar nerve block anesthesia when placing mandibular dental implants posterior to the mental foramen. J Oral Implantol. 2001;27(3):127-33. doi: 10.1563/1548-1336(2001)0272.3.CO;2.
PMID: 12500871
citation: Leith R, Lynch K, O'Connell AC. Articaine use in children: a review. Eur Arch Paediatr Dent. 2012 Dec;13(6):293-6. doi: 10.1007/BF03320829.
PMID: 23235128
citation: Gazal G. Comparison of speed of action and injection discomfort of 4% articaine and 2% mepivacaine for pulpal anesthesia in mandibular teeth: A randomized, double-blind cross-over trial. Eur J Dent. 2015 Apr-Jun;9(2):201-206. doi: 10.4103/1305-7456.156811.
PMID: 26038650
citation: Cowan A. Clinical assessment of a new local anesthetic agent-carticaine. Oral Surg Oral Med Oral Pathol. 1977 Feb;43(2):174-80. doi: 10.1016/0030-4220(77)90153-0.
PMID: 264643
citation: Srisurang S, Narit L, Prisana P. Clinical efficacy of lidocaine, mepivacaine, and articaine for local infiltration. J Investig Clin Dent. 2011 Feb;2(1):23-8. doi: 10.1111/j.2041-1626.2010.00035.x. Epub 2010 Nov 8.
PMID: 25427324
citation: Vree TB, Gielen MJ. Clinical pharmacology and the use of articaine for local and regional anaesthesia. Best Pract Res Clin Anaesthesiol. 2005 Jun;19(2):293-308. doi: 10.1016/j.bpa.2004.12.006.
PMID: 15966499
citation: Jastak JT, Yagiela JA. Vasoconstrictors and local anesthesia: a review and rationale for use. J Am Dent Assoc. 1983 Oct;107(4):623-30. doi: 10.14219/jada.archive.1983.0307. No abstract available.
PMID: 6355236
citation: Leuschner J, Leblanc D. Studies on the toxicological profile of the local anaesthetic articaine. Arzneimittelforschung. 1999 Feb;49(2):126-32. doi: 10.1055/s-0031-1300372.
PMID: 10083981
citation: Abazarpoor R, Parirokh M, Nakhaee N, Abbott PV. A Comparison of Different Volumes of Articaine for Inferior Alveolar Nerve Block for Molar Teeth with Symptomatic Irreversible Pulpitis. J Endod. 2015 Sep;41(9):1408-11. doi: 10.1016/j.joen.2015.05.015. Epub 2015 Jul 3.
PMID: 26149210
citation: Mittal M, Sharma S, Kumar A, Chopra R, Srivastava D. Comparison of Anesthetic Efficacy of Articaine and Lidocaine During Primary Maxillary Molar Extractions in Children. Pediatr Dent. 2015 Nov-Dec;37(7):520-4.
PMID: 26883609
citation: Corbett IP, Kanaa MD, Whitworth JM, Meechan JG. Articaine infiltration for anesthesia of mandibular first molars. J Endod. 2008 May;34(5):514-8. doi: 10.1016/j.joen.2008.02.042.
PMID: 18436027
citation: Pellicer-Chover H, Cervera-Ballester J, Sanchis-Bielsa JM, Penarrocha-Diago MA, Penarrocha-Diago M, Garcia-Mira B. Comparative split-mouth study of the anesthetic efficacy of 4% articaine versus 0.5% bupivacaine in impacted mandibular third molar extraction. J Clin Exp Dent. 2013 Apr 1;5(2):e66-71. doi: 10.4317/jced.50869. eCollection 2013 Apr 1.
PMID: 24455059
citation: Ram D, Peretz B. Administering local anaesthesia to paediatric dental patients -- current status and prospects for the future. Int J Paediatr Dent. 2002 Mar;12(2):80-9. doi: 10.1046/j.1365-263x.2002.00343.x.
PMID: 11966886
citation: Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth Prog. 2012 Summer;59(2):90-101; quiz 102-3. doi: 10.2344/0003-3006-59.2.90.
PMID: 22822998
citation: Vigen EC, Lasse A. Articaine hydrochloride: is it the solution? Dent Update. 2015 Jun;42(5):493. doi: 10.12968/denu.2015.42.5.493. No abstract available.
PMID: 26964452
citation: Kammerer PW, Palarie V, Daublander M, Bicer C, Shabazfar N, Brullmann D, Al-Nawas B. Comparison of 4% articaine with epinephrine (1:100,000) and without epinephrine in inferior alveolar block for tooth extraction: double-blind randomized clinical trial of anesthetic efficacy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Apr;113(4):495-9. doi: 10.1016/j.tripleo.2011.04.037. Epub 2011 Aug 6.
PMID: 22676931
citation: Pabst L, Nusstein J, Drum M, Reader A, Beck M. The efficacy of a repeated buccal infiltration of articaine in prolonging duration of pulpal anesthesia in the mandibular first molar. Anesth Prog. 2009 Winter;56(4):128-34. doi: 10.2344/0003-3006-56.4.128.
PMID: 20020793
citation: Dudkiewicz A, Schwartz S, Laliberte R. Effectiveness of mandibular infiltration in children using the local anesthetic Ultracaine (articaine hydrochloride). J Can Dent Assoc. 1987 Jan;53(1):29-31. No abstract available.
PMID: 3545399
citation: Tofoli GR, Ramacciato JC, de Oliveira PC, Volpato MC, Groppo FC, Ranali J. Comparison of effectiveness of 4% articaine associated with 1: 100,000 or 1: 200,000 epinephrine in inferior alveolar nerve block. Anesth Prog. 2003;50(4):164-8.
PMID: 14959904
citation: Sierra Rebolledo A, Delgado Molina E, Berini Aytis L, Gay Escoda C. Comparative study of the anesthetic efficacy of 4% articaine versus 2% lidocaine in inferior alveolar nerve block during surgical extraction of impacted lower third molars. Med Oral Patol Oral Cir Bucal. 2007 Mar 1;12(2):E139-44.
PMID: 17322803
citation: Wright GZ, Weinberger SJ, Marti R, Plotzke O. The effectiveness of infiltration anesthesia in the mandibular primary molar region. Pediatr Dent. 1991 Sep-Oct;13(5):278-83.
PMID: 1815200
citation: Ramadurai N, Gurunathan D, Samuel AV, Subramanian E, Rodrigues SJL. Effectiveness of 2% Articaine as an anesthetic agent in children: randomized controlled trial. Clin Oral Investig. 2019 Sep;23(9):3543-3550. doi: 10.1007/s00784-018-2775-5. Epub 2018 Dec 14.
PMID: 30552590
responsible party type: Principal Investigator
investigator affiliation: University of Campania "Luigi Vanvitelli"
investigator full name: Alfredo De Rosa
investigator title: Associated Professor
sharing ipd: No
provided document: 