Plasma Concentrations of Amoxicillin Administered in High-doses During the First Week of Treatment (MAX-AMOX)

NCT ID: NCT04070469

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-04
• Study Completion Date: 2024-12-19

Brief Summary

Amoxicillin is the most prescribed antibiotic in France. High dose intravenous amoxicillin, (dosage greater than or equal to 150 mg / kg / day or 12 g per day for patients over 80 kg) is used in the treatment, in particular, of infectious streptococcal endocarditis. oral, streptococci gallolyticus and enterococci, infections of the central nervous system with sensitive germs including Streptococcus pneumoniae and Listeria monocytogenes, osteo articular infections. The dose-related adverse effects of this antibiotic are nephrological (crystalluria may lead to acute renal failure) and neurologic. Recently, the number of amoxicillin crystalluria reported to pharmacovigilance centers has increased, having led the National Agency of drug and health products safety (ANSM) to recommend the determination of the residual level of amoxicillin during the first week of treatment of these patients. Nevertheless, there is no precise therapeutic target in patients treated with high dose amoxicillin except in the context of critical care. The authors suggest the interest of a target between 4 and 10 times the minimum inhibitory concentration (MIC) based on in vitro efficacy studies, and retrospective observations of toxicity cases.

Detailed Description

Patients will be followed for 8 days. After inclusion, (day of the introduction of high-dose amoxicillin treatment), the residual amoxicillin plasma concentrations will be determined at Day1, Day4 +/- 1 day and Day7 +/- 1 day of the start of treatment. A urine collection will be performed the same day to search for crystalluria and measure the pH and urinary density.

In case of KDIGO (Kidney Disease Improving Global Outcomes) 2 or 3 stage renal failure or neurological signs compatible with overdose, residual amoxicillin and crystalluria and urinary density and urinary pH will be measured during the day of discovery of renal failure.

In the case of KDIGO stage 1 kidney failure, a residual level of amoxicillin and a crystalluria search and the measurement of urinary density and urinary pH will be carried out the following day, when serum creatinine is checked according to usual practices.

At day 7 the clinical and infectious biological evolution of the patient will be collected.

Conditions

Infection, Bacterial

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patient reveiving amoxycillin

all patient included in this study

Group Type: EXPERIMENTAL

Amoxicillin

Intervention Type: DRUG

dosage of plasma concentration of amoxicillin

Interventions

Amoxicillin

dosage of plasma concentration of amoxicillin

Intervention Type: DRUG

Other Intervention Names

amoxicillin treatment

Eligibility Criteria

Inclusion Criteria

• Major patient, male or female, who has a bacterial infection requiring high dose intravenous amoxicillin antibiotic therapy (greater than or equal to 150 mg / kg / day with a maximum of 12 grams per day or 12 grams per day for patients over 80 kg), according to ANSM recommendations.
• Able to provide informed consent to participate.
• Covered by a Social Security scheme.

Exclusion Criteria

• Pregnant, breastfeeding, or likely to be pregnant women and in the absence of a negative pregnancy test (blood HCG beta).
• Patients under guardianship, curatorship, deprived of liberties or subject to a safeguard of justice.
• Septic shock justifying treatment with pressurized amines.
• Patient under ventilatory or circulatory support.
• Patients on dialysis at Baseline or with a creatinin clearance less than or equal to 30mL / min
• Refusal of participation
• Hypersensitivity to the active substance, to penicillins. History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam (e.g. cephalosporin, carbapenem or monobactam)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Magali VIDAL

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Locations

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Countries

France

Other Identifiers

2019-002824-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RBHP 2019 VIDAL (MAX-AMOX)

Identifier Type: -

Identifier Source: org_study_id