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Hemodynamic and Electrocardiographic Effects of Hyaluronidase Associated With Local Anaesthetics

This study has been completed.
Sponsor:
Collaborator:
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Information provided by (Responsible Party):
Mauricio Jose Tornelli, University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT01719978
First received: October 3, 2012
Last updated: October 31, 2012
Last verified: October 2012
  Purpose

Among the adjuvants to local anaesthetics (LA), the enzyme hyaluronidase is most often used as a diffuser agent of the LA in ophthalmic anaesthesia. It serves to improve clinical efficacy and prolong anaesthesia as an alternative to long-lasting and potentially more dangerous LA, especially in patients with increased cardiovascular risk. There is scarce clinical data about the safety of the use of hyaluronidase in dental procedures.

This study aimed to compare hemodynamic and electrocardiographic variables during a dental surgical procedure using a local anaesthetic associated with hyaluronidase or placebo in healthy subjects.


Condition Intervention Phase
Cardiac Arrhythmias
Drug: 3.6mL 2% Mepivacaine with 1:100,000 epinephrine
Procedure: Lower Third Molar Extraction
Drug: Hyaluronidase
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Hemodynamic and Electrocardiographic Effects of Hyaluronidase Associated With Local Anaesthetics: a Double-blind "Split-mouth" Controlled Trial.

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:
  • Arrhythmia [ Time Frame: 5min before anaesthesia ] [ Designated as safety issue: Yes ]
    Atrial or ventricular arrhythmias: isolated, paired or clustered extrasystoles, tachycardia, bradycardia and fibrillation.


Secondary Outcome Measures:
  • PR segment [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    • Duration of the PR segment, in milliseconds.

  • QRS complex [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    • Duration of the QRS complex, in milliseconds.

  • Change from baseline Heart rate [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    • Change from baseline Heart rate (evaluated period - baseline), in beats per minute. Values will be expressed as the absolute difference and the percentage of change.

  • Corrected QT [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    • Duration of the calculated corrected QT segment (QTc) in milliseconds.

  • Heart rate (absolute values) [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    • Heart rate, (absolute values) in beats per minute.


Other Outcome Measures:
  • Systolic Pressure (absolute values) [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    Systolic Blood Pressure (absolute values), in mmHg.

  • Diastolic Pressure (absolute values) [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    Diastolic Blood Pressure, in mmHg.

  • Mean Blood Pressure (absolute values) [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    Mean Blood Pressure, in mmHg.

  • Change from baseline Diastolic Pressure [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    • Change from baseline Diastolic Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.

  • Change from baseline Systolic Pressure [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    • Change from baseline Systolic Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.

  • Change from baseline Mean Arterial Blood Pressure [ Time Frame: 5min before anaesthesia; During anaesthetic injection; 5min after anaesthesia; Incision; Syndesmotomy; Luxation; Avulsion; Curetage; Suture; 1 hour after the end of surgery (At Patient discharge) and in the 7th postoperative day ] [ Designated as safety issue: Yes ]
    • Change from baseline Mean Arterial Blood Pressure (evaluated period - baseline), in mmHg. Values will be expressed as the absolute difference and the percentage of change.


Enrollment: 20
Study Start Date: October 2007
Study Completion Date: December 2011
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hyaluronidase
Lower Third Molar Extraction -- 3.6mL 2% Mepivacaine with 1:100,000 epinephrine + Hyaluronidase
Drug: 3.6mL 2% Mepivacaine with 1:100,000 epinephrine
Local anesthetic with vasoconstrictor
Other Name: Mepivacaine with epinephrine
Procedure: Lower Third Molar Extraction
Lower Third Molar Extraction with LA + hyaluronidase (or placebo)
Other Name: Molar surgery
Drug: Hyaluronidase
75RTU Hyaluronidase administration concomitant to the local anesthetic
Other Name: hyaluronidase
Placebo Comparator: Placebo
Lower Third Molar Extraction -- Anesthetic: 3.6 mL of the LA 2% HCl mepivacaine with 1:100,000 epinephrine + Placebo (0.9% saline)
Drug: 3.6mL 2% Mepivacaine with 1:100,000 epinephrine
Local anesthetic with vasoconstrictor
Other Name: Mepivacaine with epinephrine
Procedure: Lower Third Molar Extraction
Lower Third Molar Extraction with LA + hyaluronidase (or placebo)
Other Name: Molar surgery
Drug: Placebo
1mL 0.9% saline administration concomitant to the local anesthetic
Other Names:
  • Placebo
  • Saline
  • 0.9% NaCl

Detailed Description:

This double-blind crossover "split-mouth" trial evaluated the cardiovascular effects induced by 3.6 mL of the LA 2% HCl mepivacaine with 1:100,000 epinephrine, concomitantly with 75 TRU/mL hyaluronidase or placebo in inferior alveolar nerve block, for the performance of bilateral and symmetrical third molar surgery in 20 outpatients. Cardiovascular parameters, including systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR), were monitored using oscillometric and photoplethysmographic methods in 10 clinical stages. Electrocardiographic records (ECG) of 12 leads were obtained in four steps. Hyaluronidase injected concomitantly with LA did not induce changes in SBP, DBP and HR compared to placebo. There were no instances of ST segment depression, ST segment elevation, wide QRS complex extrasystoles, or narrow QRS complex extrasystoles.

To date, few studies in dentistry have investigated the effects of local anaesthetic efficacy in hyaluronidase, and even fewer have studied the relation to systemic effects induced by this interaction.

The use of LA injected concomitantly with 75 TRU/mL of hyaluronidase is safe when using this dose and route of administration.

Clinical Relevance: In dentistry, few studies have investigated the effects of hyaluronidase on local anaesthetic efficacy, and even fewer have examined the possible systemic effects induced by this interaction.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients should present bilateral lower third molars (teeth 38 and 48) for extraction and identical anatomical arrangement;
  • Absence of significant clinical morbidities, ASA I (American Society of Anesthesiologists, 1963);
  • Aged over 18 years.

Exclusion Criteria:

  • Women during pregnancy or lactation;
  • Smokers;
  • History of sensitivity to any drug used in the research;
  • Presence or history of cancer or an infectious lesion;
  • Individuals who used any medication in the last 15 days (except oral contraceptives);
  • Presence of abscess or pericoronitis in the region to be operated;
  • Patients who required supplemental anaesthesia upon anaesthetic block of the inferior alveolar nerve (post-randomisation exclusion).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01719978

Locations
Brazil
Stomatology Department, FOUSP
Sao Paulo, Brazil, 05508-000
Sponsors and Collaborators
Mauricio Jose Tornelli
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Investigators
Study Chair: Gustavo F Prado, PhD FMUSP
Study Director: Maria A Borsatti, PhD FOUSP
Study Director: Rodney G Rocha, PhD FOUSP
Study Chair: Helena R Tornelli, MD, S FOUSP
Study Chair: Renata MS Prado, MS, S FOUSP
  More Information

No publications provided

Responsible Party: Mauricio Jose Tornelli, PhD, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT01719978     History of Changes
Other Study ID Numbers: MTornelli
Study First Received: October 3, 2012
Last Updated: October 31, 2012
Health Authority: Brazil: Ethics Committee

Keywords provided by University of Sao Paulo:
Local Anaesthetics
Mepivacaine
hyaluronoglucosaminidase
Hemodynamic
Electrocardiography and Dentistry.

Additional relevant MeSH terms:
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Anesthetics
Anesthetics, Local
Epinephrine
Epinephryl borate
Mepivacaine
Racepinephrine
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Mydriatics
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sensory System Agents
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014