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

June 9, 2020 updated by: University Hospital, Clermont-Ferrand

Plasma Concentrations of Amoxicillin Administered in High-doses During the First Week of Treatment : Intra- and Inter-individual Variability, Factors Associated With Overdose and Adverse Events

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clermont-Ferrand, France, 63000
        • Recruiting
        • CHU Clermont-Ferrand
        • Sub-Investigator:
          • Bertrand SOUWEINE
        • Principal Investigator:
          • Magali Vidal
        • Contact:
        • Sub-Investigator:
          • Henri Laurichesse
        • Sub-Investigator:
          • Olivier Lesens
        • Sub-Investigator:
          • Marc André
        • Sub-Investigator:
          • Guillaume Clerfond
        • Sub-Investigator:
          • Clémence Deville
        • Sub-Investigator:
          • Marc Ruivard
        • Sub-Investigator:
          • Martin SOUBRIER

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patient reveiving amoxycillin
all patient included in this study
Drug: Amoxicillin
dosage of plasma concentration of amoxicillin
Other Names:
  • amoxicillin treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Residual plasma concentrations of administered in high doses amoxicillin
Time Frame: Day 7
research of Residual plasma concentrations of amoxicillin
Day 7
Residual plasma concentrations of administered in high doses amoxicillin
Time Frame: Day 4
research of Residual plasma concentrations of amoxicillin
Day 4
Residual plasma concentrations of administered in high doses amoxicillin
Time Frame: Day 1
research of Residual plasma concentrations of amoxicillin
Day 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
Time Frame: Day 7
research in fresh morning urine sample, examined by microscope then infrared spectroscopy in case of crystalluria
Day 7
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
Time Frame: Day 4
research in fresh morning urine sample, examined by microscope then infrared spectroscopy in case of crystalluria
Day 4
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
Time Frame: Day 1
research in fresh morning urine sample, examined by microscope then infrared spectroscopy in case of crystalluria
Day 1
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
Time Frame: day 7
plasma concentrations on blood sample
day 7
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
Time Frame: day 4
plasma concentrations on blood sample
day 4
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
Time Frame: day 1
plasma concentrations on blood sample
day 1
density of urines in g/mL
Time Frame: Day 7
research in fresh morning urine sample
Day 7
pH of urines
Time Frame: Day 7
research in fresh morning urine sample
Day 7
density of urines in g/mL
Time Frame: Day 4
research in fresh morning urine sample
Day 4
pH of urines
Time Frame: Day 4
research in fresh morning urine sample
Day 4
density of urines in g/mL
Time Frame: Day 1
research in fresh morning urine sample
Day 1
pH of urines
Time Frame: Day 1
research in fresh morning urine sample
Day 1
confusional state
Time Frame: Day 1
Glasgow coma scale
Day 1
confusional state
Time Frame: Day 4
Glasgow coma scale
Day 4
confusional state
Time Frame: Day 7
Glasgow coma scale
Day 7
encephalitic signs
Time Frame: Day 1
focal neurological signs
Day 1
encephalitic signs
Time Frame: Day 4
focal neurological signs
Day 4
encephalitic signs
Time Frame: Day 7
focal neurological signs
Day 7
epilepsy
Time Frame: Day 1
abnormal movement disorders, seizures and status epilepticus
Day 1
epilepsy
Time Frame: Day 4
abnormal movement disorders, seizures and status epilepticus
Day 4
epilepsy
Time Frame: Day 7
abnormal movement disorders, seizures and status epilepticus
Day 7
age associated with evolution of amoxicillin plasma concentrations
Time Frame: Day 0
in years
Day 0
body mass index associated with evolution of amoxicillin plasma concentrations
Time Frame: Day 0
weight in kg and height in meters will be combined to report BMI in kg/m^2
Day 0
renal function at treatment initiation associated with evolution of amoxicillin plasma concentrations
Time Frame: Day 0
CKD EPI clearance, based on serum creatinine in µmol/L
Day 0
renal function impairment during treatment
Time Frame: Day 1
stage of acute kidney injury (based on KDIGO guidelines using variation of serum creatinine in µmol/L compared with baseline, and measure of urine output)
Day 1
renal function impairment during treatment
Time Frame: Day 4
stage of acute kidney injury (based on KDIGO guidelines using variation of serum creatinine in µmol/L compared with baseline, and measure of urine output)
Day 4
renal function impairment during treatment
Time Frame: Day 7
stage of acute kidney injury (based on KDIGO guidelines using variation of serum creatinine in µmol/L compared with baseline, and measure of urine output)
Day 7
germ involved
Time Frame: Day 0
full name of bacteria
Day 0
MIC of germ
Time Frame: Day 0
MIC in mg/L
Day 0
site of infection
Time Frame: Day 0
infected organs
Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Clermont-Ferrand

Investigators

  • Principal Investigator: Magali VIDAL, University Hospital, Clermont-Ferrand

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2019

Primary Completion (Anticipated)

December 1, 2021

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

July 26, 2019

First Submitted That Met QC Criteria

August 26, 2019

First Posted (Actual)

August 28, 2019

Study Record Updates

Last Update Posted (Actual)

June 11, 2020

Last Update Submitted That Met QC Criteria

June 9, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RBHP 2019 VIDAL (MAX-AMOX)
  • 2019-002824-34 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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