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| Sponsor: | Duke University |
|---|---|
| Collaborator: |
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
| Information provided by (Responsible Party): | Duke University |
| ClinicalTrials.gov Identifier: | NCT00942084 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Herpes Simplex Virus Neonatal Sepsis |
Drug: Acyclovir |
Phase I |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | An Open Label Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants |
Plasma PK samples will be collected using a sparse sampling approach at the following sampling windows:
Dose 1:
Steady state [doses 5-6 (groups 1 and 2), doses 8-9 (group 3)]:
Last dose:
•15-18 hours after drug administration
| Estimated Enrollment: | 22 |
| Study Start Date: | September 2011 |
| Estimated Study Completion Date: | August 2012 |
| Estimated Primary Completion Date: | March 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Group 1
Gestational Age 23-29 weeks Postnatal Age < 14 days Dosage 10 mg/kg IV q12 Number of Infants 8
|
Drug: Acyclovir
Acyclovir 7mg/ml to be administered IV at 10 mg/kg IV q12 or 20 mg/kg IV q12 or 20 mg/kg IV q8 for a total of 6-9 doses(3 days).
|
|
Active Comparator: Group 2
Gestational Age 23-29 weeks Postnatal Age 14-44 days Dosage 20 mg/kg IV q12 Number of Infants 8
|
Drug: Acyclovir
Acyclovir 7mg/ml to be administered IV at 10 mg/kg IV q12 or 20 mg/kg IV q12 or 20 mg/kg IV q8 for a total of 6-9 doses(3 days).
|
|
Active Comparator: Group 3
Gestational Age 30-34 weeks Postnatal Age <45 days Dosage 20 mg/kg IV q8 Number of Infants 4
|
Drug: Acyclovir
Acyclovir 7mg/ml to be administered IV at 10 mg/kg IV q12 or 20 mg/kg IV q12 or 20 mg/kg IV q8 for a total of 6-9 doses(3 days).
|
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)
Eligibility| Ages Eligible for Study: | up to 45 Days |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
The investigator or other study site personnel will document in the source documents (e.g., the hospital chart) that informed consent was obtained. Laboratory tests or non-pharmacologic treatment procedures that were performed as standard of care within 72 hours prior to first dose of study drug may be used for screening procedures and recorded in the CRF.
Inclusion Criteria
Suspected HSV sepsis OR At least two (2) of the following
Exclusion Criteria
Contacts and Locations| Contact: Phillip B Smith, M.D. | 919-668-8951 | brian.smith@duke.edu |
| Contact: Barrie Harper, MT (ASCP) | 919-668-8291 | barrie.harper@duke.edu |
| United States, Kansas | |
| Wesely Medical Center | Recruiting |
| Wichita, Kansas, United States, 67214-4976 | |
| Contact: Paula Delmore, MSN 316-962-8555 paula.delmore@wesleymc.com | |
| Principal Investigator: Paula Delmore, MSN | |
| United States, Louisiana | |
| Tulane School of Medicine | Not yet recruiting |
| New Orleans, Louisiana, United States, 70112 | |
| Contact: Jane Reynolds, MD 504-988-5315 jreynold@tulane.edu | |
| Principal Investigator: Euming Chong, MD | |
| United States, North Carolina | |
| Duke University | Recruiting |
| Durham, North Carolina, United States, 27713 | |
| Contact: Robert W Lenfestey, M.D. 919-684-9298 lenfe001@mc.duke.edu | |
| Contact: Kim Fisher, PhD. 919-681-4913 kimberley.fisher@duke.edu | |
| Principal Investigator: Robert W Lenfestey, M.D. | |
| Principal Investigator: | Phillip B Smith, M.D. | Duke University |
More Information
| Responsible Party: | Duke University |
| ClinicalTrials.gov Identifier: | NCT00942084 History of Changes |
| Other Study ID Numbers: | Pro00028772 |
| Study First Received: | July 17, 2009 |
| Last Updated: | January 3, 2012 |
| Health Authority: | United States: Food and Drug Administration |
|
HSV Acyclovir Pharmacokinetics |
Neonate Premature Sepsis |
|
Herpes Simplex Sepsis Herpesviridae Infections DNA Virus Infections Virus Diseases Skin Diseases, Viral Skin Diseases, Infectious Skin Diseases Infection |
Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes Acyclovir Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions |
