NebuLar: Neurotoxicity Evaluation of bétalactamines in Intensive Care Unit and Identification of the Risk Factors

• Sponsor: Centre Hospitalier Universitaire, Amiens (Other)
• Overall Status: Completed
• CT.gov ID: NCT03628300
• Collaborator: (none)
• Enrollment: 214
• Actual Duration (Months): 5.9

Study Details

Study Description

Brief Summary

This retrospective cohort study included 53 patients admitted to the intensive care unit (ICU), with an average age of 69 years, without neurologic disorder before initiation of a continuous piperacillin infusion at the standard dose and who underwent piperacillin serum concentration monitoring. Among them, 23 developed a neurologic disorder for which the piperacillin causality was chronologically and semiologically suggestive. A concentration threshold of 157.2 mg/liter independently predicted neurotoxicity with 96.7% specificity and 52.2% sensitivity and may constitute a limitation when targeting less susceptible pathogens.

Condition or Disease	Intervention/Treatment	Phase
Neurotoxicity; Sepsis	Other: piperacillin serum concentration monitoring

Detailed Description

This retrospective cohort study included 53 patients admitted to the intensive care unit (ICU), with an average age of 69 years, without neurologic disorder before initiation of a continuous piperacillin infusion at the standard dose and who underwent piperacillin serum concentration monitoring. The patients included consisted of adults who received continuous intravenous (i.v.) infusion of piperacillin-tazobactam at the standard dose adjusted to the glomerular filtration rate (GFR) estimated by the modification of diet in renal disease (MDRD) formula (12 or 16 g/24 h for an estimated GFR [eGFR] of > 40 ml/liter/min/1.73 m2, 12 g/24 h for an eGFR of > 20 ml/min/1.73 m2, and 8 g/24h for an eGFR of <20 ml/min/1.73 m2) and who underwent monitoring of the piperacillin serum concentration over a 22-month period. The total serum concentration of piperacillin was measured after at least 48 h of treatment by a validated method combining high-performance liquid chromatography with photodiode array detection.

Among them, 23 developed a neurologic disorder for which the piperacillin causality was chronologically and semiologically suggestive. A concentration threshold of 157.2 mg/liter independently predicted neurotoxicity with 96.7% specificity and 52.2% sensitivity and may constitute a limitation when targeting less susceptible pathogens.

Study Design

• Study Type: Observational
• Actual Enrollment: 214 participants
• Observational Model: Case-Only
• Time Perspective: Retrospective
• Official Title: Neurotoxicity Evaluation of bétalactamines in Intensive Care Unit and Identification of the Risk Factors
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Jul 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
piperacillin serum measurement patient that underwent at least one piperacillin serum concentration monitoring	Other: piperacillin serum concentration monitoring; initiation of a continuous piperacillin infusion at the standard dose and who underwent piperacillin serum concentration monitoring.
included for analysis patient that have been included for analysis according to previously described criteria	Other: piperacillin serum concentration monitoring; initiation of a continuous piperacillin infusion at the standard dose and who underwent piperacillin serum concentration monitoring.

Outcome Measures

Primary Outcome Measures

1. Concentration-neurotoxicity relationship of piperacillin administered [22-month]

   The main objective of the study is to measure the incidence of neurological problems attributable to the use of 7 beta-lactams commonly used in intensive care: amoxicillin, piperacillin, cloxacillin, cefepime, cefotaxime, ceftazidime, ceftriaxone and to determine for the molecules studied the serum concentration value as being statistically associated with an increase in neurotoxic risk.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patient

• Social Security Affiliate

• Treated with one of the following 7 betalactamines:

• Amoxicillin

• Cloxacillin

• Piperacillin

• cefepime

• Cefotaxime

• Ceftriaxone

• Ceftazidime

Exclusion Criteria:

• All acute (at admission) or recent (less than 1 month old) neurological disorders present before the introduction of one of the beta-lactams studied will be non-inclusion criteria. These include:

• meningoencephalitis

• convulsions and uncontrolled epilepsy

• head trauma

• neurosurgical intervention

• stroke (stroke)

• tumor or cerebral lymphoma

• neurodegenerative disease and dementia

• acute drug poisoning

• Acute intoxication by narcotics, acute alcoholism

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Centre Hospitalier Universitaire, Amiens

Investigators

• Principal Investigator: Youssef Youssef, MD, CHU AMIENS

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Centre Hospitalier Universitaire, Amiens
• ClinicalTrials.gov Identifier: NCT03628300
• Other Study ID Numbers: PI2017_843_0036
• First Posted: Aug 14, 2018
• Last Update Posted: Aug 14, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Centre Hospitalier Universitaire, Amiens: neurotoxicity
• Additional relevant MeSH terms: Neurotoxicity Syndromes; Piperacillin

Study Results

No Results Posted as of Aug 14, 2018