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

Infection, Bacterial Clinical Trial

— MAX-AMOX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04070469
• Other study ID #: RBHP 2019 VIDAL (MAX-AMOX)
• Secondary ID: 2019-002824-34
• Status: Recruiting
• Phase: Phase 4
• Start date: December 4, 2019
• Est. completion date: December 2021

Study information

• Verified date: June 2020
• Source: University Hospital, Clermont-Ferrand
• Contact: Lise LACLAUTRE
• Phone: +334.73.751.195
• Email: drci[@]chu-clermontferrand.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Bacterial Infections
• Infection, Bacterial

Intervention

Drug:
• Amoxicillin
dosage of plasma concentration of amoxicillin

Locations

Country	Name	City	State
France	CHU Clermont-Ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

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