Local Anaesthetics Toxicity and Intralipid® (TOXALIP)

This study has been completed.
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01602250
First received: February 23, 2012
Last updated: November 13, 2013
Last verified: November 2012
  Purpose

The systemic toxicity of local anaesthetics may be treated using lipid emulsions ("lipid rescue"). However, there is no evidence-based proof of the efficacy of the treatment. The aim of the intended protocol is to study the effect of the emulsion Intralipid® on the toxicity prodromes in volunteers receiving either levobupivacaine or ropivacaine. After a sensitization session with lidocaine, subjects will receive in a double blind, crossover manner an i.v. infusion of levobupivacaine or ropivacaine followed by a rapid infusion of Intralipid®. The primary outcome will be the time of appearance of early neurologic signs of toxicity. In addition, the EEG and ECG will be monitored and blood sampling will be performed in order to evaluate the changes in pharmacokinetics induced by the emulsion.


Condition Intervention Phase
Toxicity
Adverse Effects
Drug: placebo
Drug: Intralipid®
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prevention of Systemic Toxicity Induced by Levobupivacaine and Ropivacaine by Intralipid®

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Duration of drug infusion [ Time Frame: less than 15 minutes ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • EEG : electroencephalogram [ Time Frame: < 15 minutes ] [ Designated as safety issue: Yes ]
    Detection of sub-clinical seizure activity

  • ECG : electrocardiogram [ Time Frame: < 15 minutes ] [ Designated as safety issue: Yes ]
    Duration of PR, QRs intervals

  • pharmacokinetics of local anesthetics (Area under the plasma concentration versus time curve (AUC)) [ Time Frame: 8 h ] [ Designated as safety issue: No ]
    blood concentration of local anesthetics during 8 hours post administration : Area under the plasma concentration versus time curve (AUC)"


Enrollment: 16
Study Start Date: January 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: levobupivacaine placebo
levobupivacaine placebo
Drug: placebo
Levobupivacaine 8 mg/min ropivacaine 8 mg/min
Other Names:
  • levobupivacaine
  • ropivacaine
Experimental: levobupivacaine Intralipid®
levobupivacaine Intralipid®
Drug: Intralipid®
Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min
Other Name: Intralipid®
Experimental: ropivacaine Intralipid®
ropivacaine Intralipid®
Drug: Intralipid®
Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min
Other Name: Intralipid®
Placebo Comparator: ropivacaine placebo
ropivacaine placebo
Drug: placebo
Levobupivacaine 8 mg/min ropivacaine 8 mg/min
Other Names:
  • levobupivacaine
  • ropivacaine

Detailed Description:

Regional anaesthesia may induce toxic neurologic and cardiac reactions related to inadvertent intravenous injection or rapid absorption of local anaesthetics. Despite the appearance of the less toxic agents ropivacaine and levobupivacaine, the problem remains. Recently, a new therapeutics called "lipid rescue" emerged. This rapid injection of a lipid emulsion is supposed to act as a lipid sink, thus delaying the release of the toxic molecules to the target organs. Animal studies as well as clinical reports seem to favour this treatment. However, there is no evidence-based proof of the efficacy of this "lipid rescue".

The aim of the study is 1) to verify the efficacy of a lipid emulsion (Intralipid® 20%) on the toxicity induced by the local anaesthetics ropivacaine and levobupivacaine and 2) to compare the effect of the emulsion on the two agents.

Sixteen volunteers with strictly normal ECG and EEG will participate to the study.

After a sensitization session with lidocaine, the subjects will receive levobupivacaine or ropivacaine i.v. at a rate of 8 mg/min (max 120 mg) followed two minutes after the beginning of infusion by a bolus injection of Intralipid® 20% or of saline 120 mL in 1 minute. The infusion of local anaesthetics will be stopped immediately at the appearance of the early signs of toxicity. In addition to the recognition of the signs by the subject (trained by the sensitization session), an anaesthesiologist will ask if the subject has any symptom. A continuous monitoring of the EEG and of the ECG will be performed.

Sixteen subjects completing the study have been considered necessary to achieve a power of 90 % with an alpha risk of 5 %. A mean time to first signs of 3.8 ± 1.2 min has been considered in the placebo groups. A 45 % difference in the primary outcome has been considered. The study will be double blind crossover as a Latin square (four treatments, four sessions, four replications).

The investigators will consider the time between infusion initiation and appearance of the early signs of toxicity as primary outcome. The secondary outcomes will be the changes in ECG and EEG variables and the pharmacokinetic parameters observed. For that purpose, blood will be sampled until the 8th hour after the beginning of local anaesthetic infusion.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Volunteers ASA1

Exclusion Criteria:

  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01602250

Locations
France
CIC plurithématique Paris-Est (CIC-9304)
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Principal Investigator: Dan Benhamou Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01602250     History of Changes
Other Study ID Numbers: P100501
Study First Received: February 23, 2012
Last Updated: November 13, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Anesthetics, local
Toxicity
Adverse effects

Additional relevant MeSH terms:
Anesthetics
Ropivacaine
Levobupivacaine
Bupivacaine
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Local
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014