Clinical trial NCT01328808: Metabolism and Toxicity of Acetaminophen
Official title: Metabolism and Toxicity of Acetaminophen in Preterm Infants
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Pain
Keywords: Acetaminophen
Preterm Infants
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
First posted: 2011-04-05
Enrollment: 31
Sex: ALL
Minimum age (years): 22
Maximum age (years): 37
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate how acetaminophen (APAP) is released into the urine and blood; to determine how the blood levels of acetaminophen and its breakdown products affect the preterm infant's health; to decrease adverse drug reactions; and to collect data on how the genetic make-up or characteristics affect how APAP is handled within the preterm infant. By taking several blood and urine samples during the study, we will be able to check the blood levels (called pharmacokinetics) of APAP in preterm babies.

Detailed description: Study procedures: The decision to replace standard intravenous morphine therapy with APAP will be made by the attending neonatologist.

Length of participation: 60 hours. No patient will be prescribed the medication specifically for the study purposes in the study protocol.

Eligibility criteria: Inclusion Criteria:

* Preterm and term neonates of both genders and all races
* a postnatal age of less than 28 days
* GA's of from 22 to less than 37 weeks
* an indwelling (peripheral or umbilical) arterial line
* a clinical indication for intravenous administration of pain relief medication

Exclusion Criteria:

* Neonates with severe asphyxia
* grade III or IV intraventricular hemorrhage, major congenital malformations/facial malformations (e.g., cleft lip and palate),
* neurological disorders
* those receiving continuous or intermittent neuromuscular blockers
* clinical or biochemical evidence of hepatic renal failure (including systemic hypoperfusion)

Primary outcomes:
measure: primary endpoint PK analysis
timeFrame: 48 hours
Secondary outcomes:
measure: Developmental stage
timeFrame: 48 hours
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Childrens Research Institute
state: District of Columbia
Study officials:
affiliation: Children's National Research Institute
name: John N van den Anker, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cook SF, Stockmann C, Samiee-Zafarghandy S, King AD, Deutsch N, Williams EF, Wilkins DG, Sherwin CM, van den Anker JN. Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model. Clin Pharmacokinet. 2016 Nov;55(11):1395-1411. doi: 10.1007/s40262-016-0408-1.
citation: Cook SF, King AD, van den Anker JN, Wilkins DG. Simultaneous quantification of acetaminophen and five acetaminophen metabolites in human plasma and urine by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: Method validation and application to a neonatal pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Dec 15;1007:30-42. doi: 10.1016/j.jchromb.2015.10.013. Epub 2015 Oct 31.
citation: Cook SF, Roberts JK, Samiee-Zafarghandy S, Stockmann C, King AD, Deutsch N, Williams EF, Allegaert K, Wilkins DG, Sherwin CM, van den Anker JN. Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm and Term Neonates: Model Development and External Evaluation. Clin Pharmacokinet. 2016 Jan;55(1):107-19. doi: 10.1007/s40262-015-0301-3.