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Trial record 8 of 113 for:    acyclovir

A Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants (PTN_Acyclo)

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ClinicalTrials.gov Identifier: NCT00942084
Recruitment Status : Completed
First Posted : July 20, 2009
Results First Posted : January 8, 2014
Last Update Posted : January 8, 2019
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Phillip Brian Smith, Duke University

Tracking Information
First Submitted Date  ICMJE July 17, 2009
First Posted Date  ICMJE July 20, 2009
Results First Submitted Date  ICMJE August 27, 2013
Results First Posted Date  ICMJE January 8, 2014
Last Update Posted Date January 8, 2019
Study Start Date  ICMJE September 2011
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
  • Clearance (CL) [ Time Frame: 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 dose
  • Volume of Distribution (V) [ Time Frame: up to 3 days of study drug administration and 10 days of safety monitoring ]
  • Half-life (T1/2) [ Time Frame: up to 3 days of study drug administration and 10 days of safety monitoring ]
  • Maximum Steady State Concentration (Cmaxss) [ Time Frame: up to 3 dasy of study drug administration and 10 days of safety monitoring ]
  • Steady State Concentration at 50% of the Dosing Interval (C50ss) [ Time Frame: up to 3 days of study drug administration and 10 days of safety monitoring ]
  • Minimum Steady State Concentration (Cminss) [ Time Frame: up to 3 days of study drug administration and 10 days of safety monitoring ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2009)
The appropriate non-compartmental pharmacokinetic parameters will be computed, including AUC, Cmax, CL, Vss, t1/2. Pharmacokinetic parameters will be summarized by patient weight. [ Time Frame: We will draw levels at 1, 2-4, and 6-8 hours after the initial dose. We will also draw levels immediately prior to, and at 1, 2-4, and 6-8 hours after a steady state dose. ]
Change History Complete list of historical versions of study NCT00942084 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants (PTN_Acyclo)
Official Title  ICMJE An Open Label Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants
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)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Herpes Simplex Virus
  • Neonatal Sepsis
Intervention  ICMJE Drug: Acyclovir

Protocol V2 & up: 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).

Protocol V1: Acyclovir 5 mg/mL to be administered IV at 500 mg/m2 IV q8h for a total of approximately 15 doses (10 days).

Study Arms  ICMJE
  • Active Comparator: Protocol V2&up-Grp1-Acyclo10 mg/kg IVq12
    Gestational Age 23-29 weeks Postnatal Age < 14 days Dosage 10 mg/kg IV q12 Number of Infants 8
    Intervention: Drug: Acyclovir
  • Active Comparator: Protocol V2&up-Grp2_Acyclo20 mg/kg IVq12
    Gestational Age 23-29 weeks Postnatal Age 14-44 days Dosage 20 mg/kg IV q12 Number of Infants 8
    Intervention: Drug: Acyclovir
  • Active Comparator: Protocol V2&up-Grp3-Acyclo20 mg/kg IVq8
    Gestational Age 30-34 weeks Postnatal Age <45 days Dosage 20 mg/kg IV q8 Number of Infants 4
    Intervention: Drug: Acyclovir
  • Protocol V1-Grps1-4-Acyclo 500 mg/m2 IVq8h
    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
    Intervention: Drug: Acyclovir
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 17, 2009)
32
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

  1. < 45 days of age at the time of initial study drug administration.
  2. Sufficient venous access to permit administration of study medication.
  3. Availability and willingness of the parent/legal guardian to provide written informed consent.
  4. Suspected HSV sepsis OR At least two (2) of the following

    • Signs of sepsis AND negative blood cultures for >24 hours7
    • Respiratory distress8
    • Lethargy8
    • Fever ≥ 38.0°C7
    • Skin lesions7,8
    • Seizures (clinical OR EEG confirmed)7
    • Irritability7
    • AST OR ALT >2 X upper limit of normal7,8
    • >20 WBCs/µL or >500 RBCs/µL7

Exclusion Criteria

  1. History of anaphylaxis attributed to acyclovir.
  2. Serum creatinine >1.7 mg/dL.
  3. Urine output <0.5 mL/kg/hour over the previous 12 hours
  4. Previous participation in the study.
  5. Concomitant condition, which in the opinion of the investigator would preclude a participant's participation in the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 45 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00942084
Other Study ID Numbers  ICMJE Pro00028772
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Phillip Brian Smith, Duke University
Study Sponsor  ICMJE Phillip Brian Smith
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: Phillip B Smith, M.D. Duke University
PRS Account Duke University
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP