A Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants (PTN_Acyclo)
- Registration Number
- NCT00942084
- Lead Sponsor
- Phillip Brian Smith
- Brief Summary
Acyclovir is a drug used to treat herpes simplex virus (HSV) infections in babies. Appropriate dosing of acyclovir is known for adults and children but acyclovir has not been adequately studied in full-term or premature neonates. HSV is a very serious infection in babies \<6 months of age and often results in death or profound mental retardation. HSV leads to profound mental retardation in young infants because the virus attacks the central nervous system.
The investigators hypothesize that the currently recommended dose of acyclovir is inadequate to produce adequate blood levels to combat herpes simplex infection. The investigators propose to study acyclovir levels in the blood of babies who are placed on acyclovir to treat a suspected HSV infection. This will allow them to determine the appropriate dose in premature infants. This is an unmet public health need because it is likely that the drug behaves differently in premature infants than it does in term infants and older children. Premature babies have more body water and less body tissue. Their kidneys are more immature and do not function as well as full term infants. Premature neonates are also at the greatest risk from herpes infection because they have poorly functioning immature immune systems. Early and appropriate treatment with acyclovir has resulted in improved outcome in term infants.
- Detailed Description
Neonatal herpes infection carries a major risk of death if untreated. Prognosis is related to disease extent and timing of therapy, making early diagnosis crucial. Mortality in the pre-antiviral era was 90% for disseminated disease and 50% for central nervous system (CNS) disease. Institution of high-dose (60 mg/kg/day) antiviral therapy with acyclovir has reduced mortality to 31% for disseminated disease and 6% for CNS disease.1 Although acyclovir has reduced mortality dramatically, morbidity remains high.
Study population: Infants \< 45 days postnatal age, suspected to have a systemic infection divided into groups by gestational and postnatal age:
Group-1: 23-29 weeks gestational age, \<14 days postnatal age Group-2: 23-29 weeks gestational age, 14-44 days postnatal age Group-3: 30-34 weeks gestational age, \<45 days postnatal age
Intravenous acyclovir will be administered for 3 days.
Timing of PK sample collection will be with respect to the end of each IV infusion. Timed PK sampling will be drawn at doses 1, and doses 5, 6, 7, 8, or 9.
Dose 1:
0-15 minutes after completion of the 1st dose; Within 30 minutes prior to administration of 2nd dose
Steady state \[doses 5 or 6 (groups 1 and 2), doses 8 or 9 (group 3)\]:
Within 30 minutes prior to dose; 0-15 minutes after completion of the dose; 2-3 hours after completion of the dose; Within 30 minutes prior to administration of the next dose
Last dose:
6-7 hours after the last dose (groups 1 and 2)and 10-11 hours after the last dose (group 3)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Protocol V2&up-Grp1-Acyclo10 mg/kg IVq12 Acyclovir Gestational Age 23-29 weeks Postnatal Age \< 14 days Dosage 10 mg/kg IV q12 Number of Infants 8 Protocol V2&up-Grp2_Acyclo20 mg/kg IVq12 Acyclovir Gestational Age 23-29 weeks Postnatal Age 14-44 days Dosage 20 mg/kg IV q12 Number of Infants 8 Protocol V2&up-Grp3-Acyclo20 mg/kg IVq8 Acyclovir Gestational Age 30-34 weeks Postnatal Age \<45 days Dosage 20 mg/kg IV q8 Number of Infants 4 Protocol V1-Grps1-4-Acyclo 500 mg/m2 IVq8h Acyclovir All patients in protocol V1 were to be dosed with 500 mg/m2 IV q8h. Protocol V1 Group 1: Gestational Age: 23-29 Weeks; PNA: \<14 days; Protocol V1 Group 2: Gestational Age: 30-42 Weeks; PNA: \<14 days; Protocol V1 Group 3: Gestational Age: 23-29 Weeks; PNA: 14-60 days; Protocol V1 Group 4: Gestational Age: 30-42 Weeks; PNA: 14-60 days
- Primary Outcome Measures
Name Time Method Clearance (CL) V1:0-5 min,2-4 hrs,6-8 hrs post Doses 1&5-15;prior to doses 5-15; V2:0-15 min post doses 1&5-15; within 30 min prior to doses 2&5-15; 2-3 hrs post doses 5-15; 15-18 hrs post last dose Timeframe:
Version 1:0-5 min,2-4 hrs,6-8 hrs post doses 1 and 5-15; prior to doses 5-15 Version 2:0-15 min post doses 1 and 5-15; within 30 min prior to doses 2 and 5-15; 2-3 hrs post doses 5-15; 15-18 hrs post last doseSteady State Concentration at 50% of the Dosing Interval (C50ss) up to 3 days of study drug administration and 10 days of safety monitoring Volume of Distribution (V) up to 3 days of study drug administration and 10 days of safety monitoring Half-life (T1/2) up to 3 days of study drug administration and 10 days of safety monitoring Maximum Steady State Concentration (Cmaxss) up to 3 dasy of study drug administration and 10 days of safety monitoring Minimum Steady State Concentration (Cminss) up to 3 days of study drug administration and 10 days of safety monitoring
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (3)
Tulane School of Medicine
🇺🇸New Orleans, Louisiana, United States
Wesely Medical Center
🇺🇸Wichita, Kansas, United States
Duke University
🇺🇸Durham, North Carolina, United States