Metabolism and Toxicity of Acetaminophen

Pain Clinical Trial

Official title:

Metabolism and Toxicity of Acetaminophen in Preterm Infants

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01328808
• Other study ID #: 4839 - APAP
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: October 2011
• Est. completion date: December 2022

Study information

• Verified date: December 2021
• Source: Children's National Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: December 2022
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Weeks to 37 Weeks

Eligibility

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)

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Acetaminophen/APAP
In preterm and term neonates with a GA of 28 weeks or more a 15 mg/kg dose of APAP will be given every 8 hrs by an intravenous infusion over 30-minute. In preterm and term neonates with a GA of less than 28 weeks a 15 mg/kg dose of APAP will be given every 8 hrs by an intravenous infusion over 30-minute

Locations

Country	Name	City	State
United States	Children's National Medical Center	Washington	District of Columbia
United States	Childrens Research Institute	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
John van den Anker

Country where clinical trial is conducted

United States, 

References & Publications (3)

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 va — View 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 Deve — View 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 Pha — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	primary endpoint PK analysis	Blood and urine levels of APAP and metabolites	48 hours
Secondary	Developmental stage	To assess both the magnitude and statistical significance of any evidence of relationship between developmental stage and toxicity-associated metabolite levels.; The analyses will also hold constant APAP dose, BID or TID and possible confounding variables such as birth order, maternal smoking status, and maternal age. We will plot the relationship between stage of development and measures of APAP Metabolism, taken at different gestational and postnatal ages. A hierarchical, cross sectional time series models will be used.	48 hours