Clinical trial NCT02545712: Safe Excipient Exposure in Neonates and Small ChildreN
Official title: Safe Excipient Exposure in Neonates and Small ChildreN - a Retrospective, Descriptive Study Off the Amount of Ethanol, Propylene Glycol, Benzyl Alcohol, Parabens, Acesulfam k, Aspartame, Glycerol, Sorbitol and Polysorbate-80 Exposed to Pediatric Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Excipient Exposure
Neonatal
Pediatric
Keywords: Ethanol
Propylene glycol
Benzyl alcohol
Acesulfam potassium
Aspartame
Glycerin
Sorbitol
Methyl-p-hydroxybenzoate
Propanyl-p-hydroxybenzoate
Patients
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
First posted: 2015-09-10
Enrollment: 630
Sex: ALL
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Neonatal patients and pediatric patients (≤ 5 years) who, at one point, have been/are being treated at the "Neonatalklinikken" (units 5021, 5023, 5024) or "BørneUngeklinikken" (units 5061, 5062, 5054, 4144) of Rigshospitalet, Denmark. To be included in the study, the patients must receive

* 2 or more different drugs if \< 28 days old
* 3 or more different drugs if 28 day ≤ 5 years old

Brief summary: The purpose of this study is to explore the quantity of excipient exposure in neonatal and young pediatric patients in a Danish Hospital. The focus will be on the preservatives ethanol, propyl glycol, benzyl alcohol, methyl-p-hydroxybenzoate and propanyl-p-hydroxybenzoate and the artificial sweeteners acesulfam potassium, aspartame, glycerol and sorbitol.

Detailed description: Studies have previously examined whether or not neonatal nor pediatric patients are exposed to excipients and what excipients they are possibly exposed to. They have shown that practically all neonatal patients receive one or more drug containing an excipient, known to be harmful. This observational study will look at both registered drugs and extemporaneous pharmaceuticals as possible sources of excipients. Based on information provided by the manufacturer (ex. the index-list), the investigator will calculate the amounts of excipients administered to the patient a week after hospitalisation. The investigator will calculate the blood alcohol content when the neonatal patient are exposed to ethanol and/or propylene glycol.

By grouping the patients according to age and subgrouping according to diagnosis/affected organ system and compare the amount of excipient exposure in each group, the study aims at identifying the most vulnerable neonatal and/or pediatric patients in terms of the amount and identity of excipients accumulated in the patient.

The study will use a descriptive, parametric statistic analysis to identify

* an average exposure rate (concentration i mg/l or amount in mg) of each of the listed excipients
* how much the average patient in each age-group is exposed to each excipient
* how much the average patient in each "affected organ system"-subgroup is exposed to each excipient

Eligibility criteria: Inclusion Criteria:

* if \< 28 days: must receive 2 or more prescriptions a day
* if 28 days ≤ 5 years: must receive 3 or more prescriptions a day
* must have been/be submitted and treated at the neonatal department (units 5021, 5023, 5024) or pediatric department (units 5061, 5062, 5054, 4144) of Rigshospitalet

Exclusion Criteria:

* no up-dated weight is listed
* \> 5 years old

Primary outcomes:
measure: Blood alcohol content measured in per mille (grams of ethanol and propylene glycol pr. kilograms of blood) in the patient
timeFrame: Single day
measure: Concentration (mg/kg/day) of benzyl alcohol in the patient
timeFrame: Single day
measure: Concentration (mg/kg/day) of acesulfam potassium in the patient
timeFrame: Single day
measure: Concentration (mg/kg/day) of aspartame in the patient
timeFrame: Single day
measure: Concentration (mg/kg/day) of glycerin in the patient
timeFrame: Single day
measure: Concentration (mg/kg/day) of sorbitol in the patient
timeFrame: Single day
measure: Concentration (mg/l) of methyl-p-hydroxybenzoate in the patient
timeFrame: Single day
measure: Concentration (mg/kg/day) of propyl-p-hydroxybenzoate in the patient
timeFrame: Single day
measure: Concentration (mg/kg/day) of polysorbate-80 in the patient
timeFrame: Single day
Secondary outcomes:
measure: Identification of patient group (according to age-interval) most vulnerable to excipient exposure (measured in number of excipients)
timeFrame: During the participants hospitalization, an expected average of 2 months
measure: Identification of patient group (according to age-interval) most vulnerable to excipient exposure (amounts of each excipient measured in (mg/l))
timeFrame: During the participants hospitalization, an expected average of 2 months
measure: Identification of patient group (according to affected organ system) most vulnerable to excipient exposure (measured in number of excipients)
timeFrame: During the participants hospitalization, an expected average of 2 months
measure: Identification of patient group (according to affected organ system) most vulnerable to excipient exposure (amounts of each excipient measured in (mg/l))
timeFrame: During the participants hospitalization, an expected average of 2 months
measure: Identification of number of patient exposed to ethanol levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to propylene glycol levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to benzyl alcohol levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to methyl-p-hydroxy-benzoate levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to propyl-p-hydroxy-benzoate levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to sodium-propyl-p-hydroxy-benzoate levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to sodium-methyl-p-hydroxy-benzoate levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to acesulfame potassium levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to aspartame levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to glycerol levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to sorbitol levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
measure: Identification of number of patient exposed to polysorbate-80 levels above tolerance levels proposed by international medicines agencies like EMA and FDA
timeFrame: Single day
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital Bispebjerg and Frederiksberg
name: Kristine Svinning Valeur, MS
role: PRINCIPAL_INVESTIGATOR
References:
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