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Pharmacokinetics (PK) of Antistaphylococcal Antibiotics in Infants (NICHD-2012-02-Staph Trio)

Phase 1
Completed
Conditions
Systemic Infection
Interventions
Registration Number
NCT01728363
Lead Sponsor
Phillip Brian Smith
Brief Summary

Multiple center, open-label, PK study

Detailed Description

Pharmacokinetics of rifampin, ticarcillin-clavulanate, and clindamycin antibiotics in hospitalized infants with suspected systemic infection or receiving one of the study drugs per local standard of care. Number of participants are 16-32 evaluable per each study drug of rifampin, ticarcillin-clavulanate, and clindamycin antibiotics.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
63
Inclusion Criteria
  • Sufficient intravascular access
  • Suspected systemic infection or receiving 1 of the study drugs per standard of care
  • informed consent from legal guardian
Exclusion Criteria
  • history of allergic reaction to study drugs
  • urine output <0.5 mL/hr/kg over the prior 24 hours
  • serum creatinine >1.7 mg/dl
  • Any condition in investigator judgment precludes participation because it could affect participant safety

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Ticarcillin-clavulanate antibioticAntibioticCohort Gestational Age (GA) Postnatal Age (PNA) Dose 1. \<30 weeks \<14 days: 75 mg/kg Q12 hrs x 6 doses 2. \<30 weeks ≥14 days-45 days 75 mg/kg Q 8 hours x 6 doses 3. \<30 weeks \>45 days-90 days 75 mg/kg Q 6 hours x 6 doses Brand name is Timentin. This drug is an antibiotic used to treat a wide variety of bacterial infections. It is a combination of two drugs \& both treat bacterial infections. Ticarcillin is a penicillin-type antibiotic that stops bacterial growth \& clavulanate potassium is an enzyme inhibitor that helps the ticarcillin work better.
Rifampin generic antibioticAntibioticCohort GA PNA Dose 1. \<32 weeks \<14 days 10 mg/kg Q 24 hours x 4 doses 2. \<32 weeks ≥14 days-120 days 15 mg/kg Q 24 hours x 4 doses 3. ≥32 weeks \<14 days 15 mg/kg Q 24 hours x 4 doses 4. ≥32 weeks ≥14 days-120 days 20 mg/kg Q 24 hours x 4 doses The brand name is Rifadin, Rimatane. This drug is an antibiotic and a first line antituberculotic and unlabeled use for infections caused by staphylococcus aureus \& staphylococcus epidermis.
Clindamycin Generic AntibioticAntibioticCohort GA PNA Dose 1. \<30 weeks \<14 days 10 mg/kg Q 12 hours x 6 doses 2. \<30 weeks ≥14 days-45 days 10 mg/kg Q 8 hours x 6 doses 3. \<30 weeks \>45 days-120 days 10 mg/kg Q 6 hours x 6 doses The brand name is Cleocin. This drug is an antibiotic used to treat a wide variety of bacterial infections and serious infections.
Primary Outcome Measures
NameTimeMethod
Cohort 1: Area under the curve infinity (AUCinfinity) for rifampin72 hours

Pharmacometric analysis of area under the curve at steady state for cohort 1 participants who were dosed with rifampin 10mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \< 14 days)

Cohort 1: Maximum concentration (Cmax) of rifampin72 hours

Pharmacometric analysis of maximum concentration after first dose for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \< 14 days)

Cohort 1: Clearance (CL) of rifampin72 hours

Pharmacometric analysis of the clearance for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \< 14 days)

Cohort 1: Volume of distribution at steady state (Vss) of rifampin72 hours

Pharmacometric analysis of volume of distribution at steady state for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \< 14 days)

Secondary Outcome Measures
NameTimeMethod
Cohort 1: Adverse events for participants receiving rifampin7 days after last study dose

Adverse events experienced by cohort 1 participants receiving rifampin 10 mg/kg Q 24 hours x 4 doses (GA \< 32 weeks, PNA \> 14 days). An adverse event is any untoward medical occurrence in humans, whether or not considered drug-related, that occurs during the conduct of a clinical trial. Any change in clinical status (routine labs, physical examinations, etc.) that is considered clinically significant

Cohort 1 participants: serious adverse events for participants receiving rifampin7 days after last study dose

Serious adverse events experienced by cohort 1 participants receiving rifampin 10 mg/kg Q 24 hours x 4 doses(GA \< 32 weeks, PNA \> 14 days)Any event that results in any of the following outcomes: death, life-threatening adverse vent, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, inpatient hospitalization or prolongation of existing hospitalization, or important medical event that may jeopardize the health of the study participant or require medical or surgical intervention to prevent another outcome listed above

Trial Locations

Locations (10)

University of Louisville

🇺🇸

Louisville, Kentucky, United States

Duke University

🇺🇸

Durham, North Carolina, United States

Kings County Hospital Center

🇺🇸

Brooklyn, New York, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

University of FL

🇺🇸

Gainesville, Florida, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

University of Texas Children's Hospital

🇺🇸

Galveston, Texas, United States

UFL Health and Baptist

🇺🇸

Jacksonville, Florida, United States

Wesley Medical

🇺🇸

Wichita, Kansas, United States

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