ToxicityPhase 2TOXALIPNCT01602250
Local Anaesthetics Toxicity and Intralipid®
A Phase 2 study testing Intralipid® in people with Toxicity and Adverse Effects, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Toxicity, Adverse Effects
- What is being tested?
- Intralipid®
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2011to Aug 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Volunteers ASA1
Who cannot join
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prevention of Systemic Toxicity Induced by Levobupivacaine and Ropivacaine by Intralipid®
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.
Read the 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.
- Conditions
- Toxicity, Adverse Effects
- Being tested
- placebo, Intralipid®
- Keywords
- Anesthetics, local, Toxicity, Adverse effects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboDrug
Also called levobupivacaine, ropivacaine
Levobupivacaine 8 mg/min ropivacaine 8 mg/min
Intralipid®Drug
Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min
| Study group | Role | What they receive |
|---|---|---|
| levobupivacaine placebo | Placebo comparator | levobupivacaine placebo Receives: Drug: placebo |
| levobupivacaine Intralipid® | Experimental | levobupivacaine Intralipid® Receives: Drug: Intralipid® |
| ropivacaine Intralipid® | Experimental | ropivacaine Intralipid® Receives: Drug: Intralipid® |
| ropivacaine placebo | Placebo comparator | ropivacaine placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of drug infusion
Measured: less than 15 minutes
Secondary outcomes (3)
EEG : electroencephalogram
Detection of sub-clinical seizure activity
Measured: < 15 minutes
ECG : electrocardiogram
Duration of PR, QRs intervals
Measured: < 15 minutes
pharmacokinetics of local anesthetics (Area under the plasma concentration versus time curve (AUC))
blood concentration of local anesthetics during 8 hours post administration : Area under the plasma concentration versus time curve (AUC)"
Measured: 8 h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2012 (estimated)
- Study startJan 2011
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ToxicityStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dan Benhamou, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01602250
- Sponsor's protocol ID
- P100501
- Acronym
- TOXALIP
- Status last verified
- Nov 2012
- First submitted
- 23 Feb 2012
- Last updated
- 21 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27404223
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Systemic Toxicity Induced by Levobupivacaine and Ropivacaine by Intralipid®
- ClinicalTrials.gov ID
- NCT01602250
- Acronym / sponsor ID
- TOXALIP / P100501
- Conditions
- Toxicity, Adverse Effects
- Keywords
- Anesthetics, local, Toxicity, Adverse effects
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- Jan 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 18 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| levobupivacaine placebo | Placebo comparator | Drug: placebolevobupivacaine placebo |
| levobupivacaine Intralipid® | Experimental | Drug: Intralipid®levobupivacaine Intralipid® |
| ropivacaine Intralipid® | Experimental | Drug: Intralipid®ropivacaine Intralipid® |
| ropivacaine placebo | Placebo comparator | Drug: placeboropivacaine placebo |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Volunteers ASA1
Key exclusion criteria (1 listed)
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placeboAlso: levobupivacaine, ropivacaineLevobupivacaine 8 mg/min ropivacaine 8 mg/min | Drug | levobupivacaine placebo, ropivacaine placebo |
| Intralipid®Levobupivacaine 8 mg/min ropivacaine 8 mg/min Intralipid® 120 ml in one min | Drug | levobupivacaine Intralipid®, ropivacaine Intralipid® |
Primary outcome
Duration of drug infusion
Time frame: less than 15 minutes
3 secondary outcomes
EEG : electroencephalogram
Time frame: < 15 minutes
ECG : electrocardiogram
Time frame: < 15 minutes
pharmacokinetics of local anesthetics (Area under the plasma concentration versus time curve (AUC))
Time frame: 8 h
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2016.
- Results publication: PubMed 27404223Dureau 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dan Benhamou principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intralipid® in people with Toxicity and Adverse Effects, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of drug infusion (time frame: less than 15 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01602250, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2016.