Comparison of the Efficacy and Safety of Two Homologous Active Principles for Local Dental Anesthesia
Condition: Drug Effect; Tooth Extraction
Study type: Interventional
Phase: Phase 4

Summary: 
      In the complexity of the Dental care the third molar surgery is one of the most common
      procedures, it is indicated for multiple reasons like infections in root canal, prosthetics
      or even esthetical purposes. This surgery can be safely performed with the help of local
      anesthetics, due to their quick action, and reversibility to control pain, reducing possible
      complications during and after the surgeries.

      Among the different types of local anesthetics used in dentistry, the articaine bears
      characteristics that provide some advantages compared to similar anesthetics like Lidocaine,
      being one of the most used anesthetics worldwide. Different authors have concluded that it is
      a safe when used in patients at different ages and it is effective as a local anesthetic in
      the majority of procedures. It is important for dentists to know the differences or
      similarities of anesthetics in terms of their effects, safety, dosages required in patients
      undergoing surgical removal of teeth, as well as the mechanism of action and pharmacological
      properties, in order to take advantage of its benefits and minimize risks.

      This study aims to test the efficacy and safety of an anesthetic solution, based on the same
      active molecule, articaine, manufactured by two different commercial houses, one domestic and
      one international, in order to gather scientific evidence and to show that they are not
      different. This will provide scientific results to help in the selection of any of these
      brands to be used with confidence in the dental practice. This will strengthen the
      collaboration between the academy and the companies, which would allow them to improve the
      quality of their products.

      Locally there are no studies available comparing the articaine-type anesthetic with
      epinephrine at the same concentration, manufactured locally by a national company, to a
      foreign one, which is an important opportunity to expand the knowledge and create scientific
      reports, about what a local anesthetic is and what it does.

      Finally, this study would contribute to the need to guarantee the quality of medicines in
      Colombia, by means of compliance with the legal provisions contemplated in resolution 1890 of
      November 2001 and 1400 of August 2001, issued by the Ministry of Health of Colombia :
      "Requirements to demonstrate the therapeutic effectiveness, through studies of
      Bioavailability and Bioequivalence of medicines for a special group of them.
    

Detailed description: 
      Local anesthetic:

      Local anesthetics are widely used in dentistry for different procedures and are chemical
      substances that block nerve conduction, temporarily and irreversibly in order to avoid pain
      and are placed in specific sites of the body, for example in oral tissues.

      Pharmacology of local anesthetics related to effectiveness and safety

      Latency time It is defined as the time that elapses between the infiltration of the
      anesthetic substance in the tissue until the first signs of insensibility are felt. It is
      influenced by the distance of the route the anesthetic must travel, with the ability to cross
      the membrane of the nerve cells.

      Duration of the anesthetic effect Also known as the duration of the action, related to the
      capacity of fixation of the anesthetic substance to the nerve cell proteins and with lipid
      solubility.

      pH of anesthetics It is one of the factors that influence the action of blocking nerve
      conduction, and is the factor that conditions the movement of the anesthetic from the site
      where it is administered to the nerve fiber, that is why the tissues that are infected make
      the effectiveness is decreased, since the pH would turn acidic. In addition, the pH varies
      according to whether or not it has a vasoconstrictor.

      Power Anesthetic capacity to pass the lipids of the nerve membranes, the greater the
      liposolubility, the greater the anesthetic power, depending on how the power is the
      classification of the action time, low power with short action, intermediate power with
      action medium and high power with long action.

      Diffusion It is related to the minimum concentration required to inhibit nerve conduction,
      given by the transfer of molecules or ions from an anesthetic solution from the point where
      it infiltrates to the membrane of the nerve cell.

      Articaine

      Articaine is a short-acting local anesthetic, belonging to the group of amides, it has an
      additional ester group that is rapidly hydrolyzed by plasma esterases, which exhibits a lower
      toxicity compared to other drugs of the same family. This dissolves better than other amides
      in the soft tissues and bone, for this reason, it is especially indicated for dental use.

      Articaine is introduced in 1972 in the market of local anesthetics. Prepared for the first
      time by Rusching et al in 1969, it changed its generic name to articaine when it began to be
      used in clinical practice in Germany in 1976. Its use gradually expanded, until it entered
      the market of the United States and Canada, in 1983 and in the United Kingdom in 1998.

      Articaine with vasoconstrictor (epinephrine) is administered submucosally. The onset of
      anesthetic effects is observed between 1 to 6 minutes and the duration of anesthesia is
      approximately one hour and is recommended for long procedures. After administration, maximum
      concentrations are reached after 20 minutes, approximately between 60 and 80% bind plasma
      proteins, in particular albumin and gamma globulins, and are easily distributed in soft
      tissues.

      Its main metabolite is the articainic acid, which is metabolized by the isoenzymes of the
      cytochrome P450, between 5 and 10% of the articainic acid; this causes the increase of the
      elimination, half-life to 90 minutes. The drug is eliminated in the urine as articainic acid,
      as glucuronide of the articainic acid and as articaine without metabolizing.

      The administration of vasoconstrictors such as epinephrine, together with an anesthetic,
      could cause increases in blood pressure or heart rate due to higher plasma levels, however,
      these adverse effects are uncommon.

      Patients receiving local anesthesia for dental treatments may experience side effects at the
      level of the Central Nervous System (CNS), in case of receiving an intra-arterial injection
      with reflux into the cerebral circulation. Patients with peripheral vascular diseases and
      hypertension may experience an exaggerated response when treated with articaine-epinephrine
      due to the vasoconstrictive effects of epinephrine, which can be especially intense in the
      elderly.

      Because of its bisulfite content (as a preservative of epinephrine), the preparations of
      articaine-epinephrine are contraindicated in patients with hypersensitivity to bisulfite. In
      addition, patients with asthma are usually more susceptible than others to this
      hypersensitivity.

      There are few studies evaluating the pharmacokinetics of articaine in the elderly or in
      patients with renal or hepatic insufficiency, although caution is advised when administering
      articaine-epinephrine to patients with liver diseases, as these patients are more susceptible
      to the drug's potential toxicity and Dose reductions may be necessary. It should also be
      administered with caution in patients with a history of drug abuse because the adverse
      reactions are dose-related and in elderly patients should be dosed with the minimum effective
      dose.
    

Intervention name(s): Articaine / EPINEPHrine Cartridge
Intervention type(s): Drug
Intervention description(s): The day scheduled for the surgery, vital signs (pulse, blood pressure and oxygen saturation) will be recorded prior the administration of the anesthesia. A volume of 1.8 ml of 4% articaine and epinephrine 1: 100000 solution of either the test product or the reference product will be deposited slowly to proceed to the inferior alveolar nerve block (IANB), according to the table of allocation of treatments in each period. The vital signs will continue to be monitored during the procedure, and once the procedure has been completed. If the volunteer needs more anesthetic, this will be recorded and will be administrated according to the maximum permitted doses (7 mg / kg (up to 500 mg) 5 mg / kg in children 7), and immediately after the administration, the vital signs will be taken again.
Intervention MeSH terms: Epinephrine; Carticaine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Open, randomized, double blind, controlled, phase 4 crossover, randomized clinical trial will be conducted to compare the efficacy and clinical safety of two homologous active principles, articaine HCl with 1: 100,000 epinephrine (test) against the reference formulation 4% articaine HCl with 1: 100,000 of epinephrine, used intraorally in extraction of retained third molars (18), and will be carried out in the Faculty of Dentistry of the University of Antioquia
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Health Services Research
Keywords: Articaine; IANB; Third molar surgery; Non-inferiority; Local anesthesia