Non-interventional post-authorization study on effectiveness of reversal of local anaesthesia and on the occurrence of local reactions and cardiovascular adverse events in patients treated with OraVerse® versus patients not treated with OraVerse® (control group) in Germany (ORAPAES)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Prospective, post-authorization study

Study drug and medical condition

• Name of medicine, other:
  OraVerse
• Medical condition to be studied:
  Cardiovascular disorder

Population studied

• Short description of the study population:
  Patients treated with OraVerse® and not treated with OraVerse® (control group) after local anaesthetic procedures in routine clinical practice.; ; Patients eligible for ORAPAES were those; 1. who underwent local anesthesia by intraoral, submucosal injection of a local anesthetic containing a catecholamine vasoconstrictor, such as epinephrine (adrenaline) (dilution 1:100,000 or 1:200,000), after a routine dental procedure such as teeth cleaning, calculus removal, scaling and root planing, and restoration; preparation including crown preparation;; 2. Who were at least 6 years old and weighed at least 15 kilograms (33.1 pounds);; 3. For whom the dentist had made a decision to administer PM independent of the participation in the study;; 4. who had signed an informed consent form; ; Patients eligible for ORANIS were patients; 1. who received local anesthesia by intraoral submucosal injection of a local anesthetic solution containing a catecholamine vasoconstrictor, such as epinephrine; (dilution 1:100,000 or 1:200,000), after a routine dental procedure (teeth cleaning, scaling and root planing, restoration preparation, or preparation for crowns);; 2. who were at least 18 years old; -those for whom the dentist had made a decision to administer PM independent of this documentation;; 3. who had signed an informed consent, and were included consecutively, if eligible.
• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  672

Study design details

• Main study objective:
  -To compare time to recovery of normal sensation in the lip/tongue among patients treated with OraVerse® and not treated with OraVerse® (control group) after local anaesthetic procedures in routine clinical practice; -To compare time to recovery of normal function (eating, drinking and speaking) among patients treated with OraVerse® and not treated with OraVerse® (control group) after local anaesthetic procedures in routine clinical practice
• Outcomes:
  •Primary outcomes: Effectiveness. The primary outcomes will be the sensory and functional assessment measured by the patient the day of OraVerse® administration and collected the day after OraVerse® administration. •the patient reported time to recovery to normal:•sensation of upper lip, lower lip and tongue•functionality (speaking, drinking, eating), ; •Secondary outcomes: Safety. The secondary outcomes of the study will be the frequency of local reactions (post-procedural pain, injection site pain, injection site reaction) and cardiovascular acute events (bradycardia, tachycardia, hypertension, hypotension, cardiac arrhythmia) which will be collected by the dentist prior to discharge and during a phone call to the patient the day following the dental procedure.
• Data analysis plan:
  •Primary objective: estimated median and corresponding 95% confidence interval of the time to recovery of normal sensation of the lip and tongue and of the time to recovery of functionality for each group (OraVerse® and control) will be calculated using the Kaplan-Meier method. (Stratified) log-rank-tests will be used to compare the survival curves of the 2 treatment groups. A Cox model with treatment group and potential confounders will be used to estimate the hazard ratio (HR) of outcome of interest using the control group as reference.; •Secondary objective: estimated frequency and corresponding 95% confidence interval of local reactions, cardiovascular events and cardiovascular events leading to healthcare consultation will be described for each group (OraVerse® and control). Logistic regression model will be used to estimate odds ratios (OR) to compare the frequency of local reactions between treatments groups after adjustment on potential confounders.