Reversing the Effects of 0.5% Bupivacaine

Reversing the Effects of 0.5% Bupivacaine: A Randomized Controlled Trial

Clinical trials have shown phentolamine mesylate (PM), brand name OraVerse, to be effective at reducing the amount of time to reversal of local anesthesia with different dental anesthetics. However, to date no study investigated the efficacy of phentolamine mesylate to reverse anesthesia induced with the use of Bupivacaine.

The objective of the proposed research is to conduct a pilot-scale randomized clinical trial evaluating the difference in time required for the return of normal soft-tissue sensation and function in participants who have received 0.5% Bupivacaine HCl, 1:200,000 epinephrine, followed by an injection with either 1) OraVerse (phentolamine mesylate) or 2) sterile physiological water (control).

Study Overview

• Status: Completed
• Conditions: Anesthesia, Local
• Intervention / Treatment: Drug: Saline Water (Control); Drug: OraVerse

Detailed Description

Dental procedures often require the use of local anesthesia. The most common local anesthetic used is 2% Lidocaine 1:100,000 epinephrine. This local anesthetic can achieve soft tissue anesthesia for 180-300 minutes and pulpal anesthesia for 60 minutes. Unfortunately, for longer treatments this relatively short duration can lead to the loss of anesthetic effect before the end of the interventions. Time-demanding dental appointments include oral and periodontal surgeries, extensive restorative treatments, and even minor treatments when completed by dental students. Unfortunately, if a short acting anesthetic such as Lidocaine is being used during long lasting procedures, once the patients start feeling pain again, it may be difficult to reestablish deep pulpal anesthesia with a repeated injection due to tachyphylaxis. To avoid this situation long-acting local anesthetics could be selected instead. The only long-acting anesthetic available in dentistry is 0.5% Bupivacaine HCl, 1:200,000 epinephrine. Bupivacaine can produce soft tissue anesthesia for up to 12 hours (commonly 4 to 9 hours) and pulpal anesthesia for up to 7 hours (commonly 1.5 to 3 hours). Unfortunately, Bupivacaine is not often used for non-surgical procedures due to its very long soft tissue anesthesia that outlast treatments by several hours.

The effects of soft tissue anesthesia linger for some time after the administration of long acting local anesthetics such as Bupivacaine. This can lead to discomfort and occasionally injury from lip/tongue biting. Clinical trials have shown phentolamine mesylate (PM), brand name OraVerse, to be effective at reducing the amount of time to reversal of local anesthesia with different dental anesthetics. However, to date no study investigated the efficacy of phentolamine mesylate to reverse anesthesia induced with the use of Bupivacaine.

The objective of the proposed research is to conduct a pilot-scale randomized clinical trial evaluating the difference in time required for the return of normal soft-tissue sensation and function in participants who have received 0.5% Bupivacaine HCl, 1:200,000 epinephrine, followed by an injection with either 1) OraVerse (phentolamine mesylate) or 2) sterile physiological water (control). This will further advance our knowledge of both Bupivacaine and phentolamine mesylate as there are no current studies evaluating reversing the effect of Bupivacaine with PM.

It is hypothesized that phentolamine mesylate will reduce the duration of soft tissue anesthesia by 2.5 hours when compared with a control injection of saline water. It is anticipated that this study will determine the feasibility and sample size needed to conduct a full-scale multi-centre trial.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 4R2
      • Dalhousie University Faculty of Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age or older
• capable of providing informed consent

Exclusion Criteria:

• contra-indications for regular dental treatment
• medical history that contraindicates the use of epinephrine
• participant taken an opioid or an opioid like analgesic within 24 hours
• pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; 1.7ml saline water	Drug: Saline Water (Control); 1.7ml saline water will be injected once after the participants are found to be well anesthetized following an injection of 1.8ml Bupivacaine 0.5% (inferior alveolar nerve block). The water will be injected at the same site Bupivacaine was injected.; Other Names: Placebo
Experimental: OraVerse; 1.7ml OraVerse	Drug: OraVerse; 1.7ml OraVerse (0.4 mg phentolamine mesylate) will be injected once after the participants are found to be well anesthetized following an injection of 1.8ml Bupivacaine 0.5% (inferior alveolar nerve block). Oraverse will be injected at the same site Bupivacaine was injected.; Other Names: phentolamine mesylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to reversal of local anesthesia	8 hours

Collaborators and Investigators

• Sponsor: Dalhousie University
• Investigators: Principal Investigator: Pierre-Luc Michaud, DMD, MSc, FRCDC, Dalhousie University

Publications and helpful links

Helpful Links

• Dalhousie University Faculty of Dentistry Web Site

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2017
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): September 15, 2019

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 15, 2016
• First Posted (Estimate): December 16, 2016

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 27, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-Antagonists; Phentolamine
• Other Study ID Numbers: 2016-4014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Aggregate data to be published in peer reviewed journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No