Safe Excipient Exposure in Neonates and Small ChildreN

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Excipient Exposure, Neonatal, Pediatric

Intervention / Treatment
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* Other: Exposure to ethanol
* Other: Exposure to propylene glycol
* Other: Exposure to benzyl alcohol
* Other: Exposure to acesulfam potassium
* Other: Exposure to aspartame
* Other: Exposure to glycerol
* Other: Exposure to sorbitol
* Other: Exposure to methyl-p-hydroxybenzoate
* Other: Exposure to propanyl-p-hydroxybenzoate
* Other: Exposure to polysorbate-80


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Neonatal patients<br>Receiving 2 or more drugs at one day during their hospitalisation. For each drug, it is listed whether it is an extemporaneous, registered, the preparation, dosis, amount, interval, formulation and route of administration. It is noted if the drug contains ethanol, propylene glycol, benzyl alcohol, methyl-p-hydroxybenzoate, propanyl-p-hydroxybenzoate, acesulfam potassium, aspartame, glycerin and/or sorbitol. | Other: Exposure to ethanol<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: Ethyl achohol;Other: Exposure to propylene glycol<br>* The drug source(s) and amount administered daily are noted.<br>Other: Exposure to benzyl alcohol<br>* The drug source(s) and amount administered daily are noted.<br>Other: Exposure to acesulfam potassium<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: Acesulfame-K;Other: Exposure to aspartame<br>* The drug source(s) and amount administered daily are noted.<br>Other: Exposure to glycerol<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: Glycerol;Other: Exposure to sorbitol<br>* The drug source(s) and amount administered daily are noted.<br>Other: Exposure to methyl-p-hydroxybenzoate<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: including sodium-methyl-p-hydroxybenzoate;Other: Exposure to propanyl-p-hydroxybenzoate<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: including sodium-propanyl-p-hydroxybenzoate;Other: Exposure to polysorbate-80<br>* The drug source(s) and amount administered daily are noted.<br>|
| Pediatric patients (28 days ≤ 5 years)<br>Receiving 3 or more drugs at one day during their hospitalisation. For each drug, it is listed whether it is an extemporaneous, registered, the preparation, dosis, amount, interval, formulation and route of administration. It is noted if the drug contains ethanol, propylene glycol, benzyl alcohol, methyl-p-hydroxybenzoate, propanyl-p-hydroxybenzoate, acesulfam potassium, aspartame, glycerin and/or sorbitol. | Other: Exposure to ethanol<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: Ethyl achohol;Other: Exposure to propylene glycol<br>* The drug source(s) and amount administered daily are noted.<br>Other: Exposure to benzyl alcohol<br>* The drug source(s) and amount administered daily are noted.<br>Other: Exposure to acesulfam potassium<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: Acesulfame-K;Other: Exposure to aspartame<br>* The drug source(s) and amount administered daily are noted.<br>Other: Exposure to glycerol<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: Glycerol;Other: Exposure to sorbitol<br>* The drug source(s) and amount administered daily are noted.<br>Other: Exposure to methyl-p-hydroxybenzoate<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: including sodium-methyl-p-hydroxybenzoate;Other: Exposure to propanyl-p-hydroxybenzoate<br>* The drug source(s) and amount administered daily are noted.<br>* Other names: including sodium-propanyl-p-hydroxybenzoate;Other: Exposure to polysorbate-80<br>* The drug source(s) and amount administered daily are noted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood alcohol content measured in per mille (grams of ethanol and propylene glycol pr. kilograms of blood) in the patient | Both concentrations of ethanol and propylene glycol are included in the calculations. with propylene glycol 1/3 as intoxicating as ethanol. | Single day | 
| Concentration (mg/kg/day) of benzyl alcohol in the patient |  | Single day | 
| Concentration (mg/kg/day) of acesulfam potassium in the patient |  | Single day | 
| Concentration (mg/kg/day) of aspartame in the patient |  | Single day | 
| Concentration (mg/kg/day) of glycerin in the patient |  | Single day | 
| Concentration (mg/kg/day) of sorbitol in the patient |  | Single day | 
| Concentration (mg/l) of methyl-p-hydroxybenzoate in the patient |  | Single day | 
| Concentration (mg/kg/day) of propyl-p-hydroxybenzoate in the patient |  | Single day | 
| Concentration (mg/kg/day) of polysorbate-80 in the patient |  | Single day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of patient group (according to age-interval) most vulnerable to excipient exposure (measured in number of excipients) | The excipients (ethanol, propylene glycol, benzyl alcohol, methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, acesulfam potassium, aspartame, glycerol, polysorbate-80 and sorbitol) will be ranked according to which excipient is most often present in the medicine administered to the patients. | During the participants hospitalization, an expected average of 2 months | 
| Identification of patient group (according to age-interval) most vulnerable to excipient exposure (amounts of each excipient measured in (mg/l)) | The excipients (ethanol, propylene glycol, benzyl alcohol, methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, acesulfam potassium, aspartame, glycerol, polysorbate-80 and sorbitol) will be ranked according to which excipient is most often present in the medicine administered to the patients. | During the participants hospitalization, an expected average of 2 months | 
| Identification of patient group (according to affected organ system) most vulnerable to excipient exposure (measured in number of excipients) | The excipients (ethanol, propylene glycol, benzyl alcohol, methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, acesulfam potassium, aspartame, glycerol, polysorbate-80 and sorbitol) will be ranked according to which excipient is most often present in the medicine administered to the patients. | During the participants hospitalization, an expected average of 2 months | 
| Identification of patient group (according to affected organ system) most vulnerable to excipient exposure (amounts of each excipient measured in (mg/l)) | The excipients (ethanol, propylene glycol, benzyl alcohol, methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, acesulfam potassium, aspartame, glycerol, polysorbate-80 and sorbitol) will be ranked according to which excipient is most often present in the medicine administered to the patients. | During the participants hospitalization, an expected average of 2 months | 
| Identification of number of patient exposed to ethanol levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of ethanol to daily tolerance limit | Single day | 
| Identification of number of patient exposed to propylene glycol levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of proplyene glycol to daily tolerance limit | Single day | 
| Identification of number of patient exposed to benzyl alcohol levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of benzyl alcohol to daily tolerance limit | Single day | 
| Identification of number of patient exposed to methyl-p-hydroxy-benzoate levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of methyl-p-hydroxy-benzoate to daily tolerance limit | Single day | 
| Identification of number of patient exposed to propyl-p-hydroxy-benzoate levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of propyl-p-hydroxy-benzoate to daily tolerance limit | Single day | 
| 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 | Comparison of each patient daily exposure rate of sodium-propyl-p-hydroxy-benzoate to daily tolerance limit | Single day | 
| 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 | Comparison of each patient daily exposure rate of sodium-methyl-p-hydroxy-benzoate to daily tolerance limit | Single day | 
| Identification of number of patient exposed to acesulfame potassium levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of acesulfame potassium to daily tolerance limit | Single day | 
| Identification of number of patient exposed to aspartame levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of aspartame to daily tolerance limit | Single day | 
| Identification of number of patient exposed to glycerol levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of glycerol to daily tolerance limit | Single day | 
| Identification of number of patient exposed to sorbitol levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of sorbitol to daily tolerance limit | Single day | 
| Identification of number of patient exposed to polysorbate-80 levels above tolerance levels proposed by international medicines agencies like EMA and FDA | Comparison of each patient daily exposure rate of polysorbate-80 to daily tolerance limit | Single day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ethanol, Propylene glycol, Benzyl alcohol, Acesulfam potassium, Aspartame, Glycerin, Sorbitol, Methyl-p-hydroxybenzoate, Propanyl-p-hydroxybenzoate, Patients