Ignite Creation Date:
2025-12-24 @ 5:05 PM
Ignite Modification Date:
2025-12-30 @ 12:13 PM
Study NCT ID:
NCT01602250
Status:
COMPLETED
Last Update Posted:
2016-12-21
First Post:
2012-02-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Local Anaesthetics Toxicity and Intralipid®
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077554', 'term': 'Levobupivacaine'}, {'id': 'D000077212', 'term': 'Ropivacaine'}, {'id': 'C545823', 'term': 'soybean oil, phospholipid emulsion'}], 'ancestors': [{'id': 'D002045', 'term': 'Bupivacaine'}, {'id': 'D000813', 'term': 'Anilides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000814', 'term': 'Aniline Compounds'}, {'id': 'D000588', 'term': 'Amines'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 16}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2012-11', 'completionDateStruct': {'date': '2013-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-12-20', 'studyFirstSubmitDate': '2012-02-23', 'studyFirstSubmitQcDate': '2012-05-16', 'lastUpdatePostDateStruct': {'date': '2016-12-21', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2012-05-18', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Duration of drug infusion', 'timeFrame': 'less than 15 minutes'}], 'secondaryOutcomes': [{'measure': 'EEG : electroencephalogram', 'timeFrame': '< 15 minutes', 'description': 'Detection of sub-clinical seizure activity'}, {'measure': 'ECG : electrocardiogram', 'timeFrame': '< 15 minutes', 'description': 'Duration of PR, QRs intervals'}, {'measure': 'pharmacokinetics of local anesthetics (Area under the plasma concentration versus time curve (AUC))', 'timeFrame': '8 h', 'description': 'blood concentration of local anesthetics during 8 hours post administration : Area under the plasma concentration versus time curve (AUC)"'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Anesthetics, local', 'Toxicity', 'Adverse effects'], 'conditions': ['Toxicity', 'Adverse Effects']}, 'referencesModule': {'references': [{'pmid': '27404223', 'type': 'RESULT', 'citation': 'Dureau P, Charbit B, Nicolas N, Benhamou D, Mazoit JX. Effect of Intralipid(R) on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study. Anesthesiology. 2016 Sep;125(3):474-83. doi: 10.1097/ALN.0000000000001230.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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".\n\nThe 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.\n\nSixteen volunteers with strictly normal ECG and EEG will participate to the study.\n\nAfter 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.\n\nSixteen 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).\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '40 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Volunteers ASA1\n\nExclusion Criteria:\n\n* Pregnancy'}, 'identificationModule': {'nctId': 'NCT01602250', 'acronym': 'TOXALIP', 'briefTitle': 'Local Anaesthetics Toxicity and Intralipid®', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Prevention of Systemic Toxicity Induced by Levobupivacaine and Ropivacaine by Intralipid®', 'orgStudyIdInfo': {'id': 'P100501'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'levobupivacaine placebo', 'description': 'levobupivacaine placebo', 'interventionNames': ['Drug: placebo']}, {'type': 'EXPERIMENTAL', 'label': 'levobupivacaine Intralipid®', 'description': 'levobupivacaine Intralipid®', 'interventionNames': ['Drug: Intralipid®']}, {'type': 'EXPERIMENTAL', 'label': 'ropivacaine Intralipid®', 'description': 'ropivacaine Intralipid®', 'interventionNames': ['Drug: Intralipid®']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'ropivacaine placebo', 'description': 'ropivacaine placebo', 'interventionNames': ['Drug: placebo']}], 'interventions': [{'name': 'placebo', 'type': 'DRUG', 'otherNames': ['levobupivacaine', 'ropivacaine'], 'description': 'Levobupivacaine 8 mg/min ropivacaine 8 mg/min', 'armGroupLabels': ['levobupivacaine placebo', 'ropivacaine placebo']}, {'name': 'Intralipid®', 'type': 'DRUG', 'description': 'Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min', 'armGroupLabels': ['levobupivacaine Intralipid®', 'ropivacaine Intralipid®']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75013', 'city': 'Paris', 'country': 'France', 'facility': 'CIC plurithématique Paris-Est (CIC-9304)', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}], 'overallOfficials': [{'name': 'Dan Benhamou', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Assistance Publique - Hôpitaux de Paris'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'collaborators': [{'name': 'Institut National de la Santé Et de la Recherche Médicale, France', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'SPONSOR'}}}}