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

Primary Purpose

Systemic Infection

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Antibiotic
Sponsored by
Phillip Brian Smith
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Infection focused on measuring Staphylococcal

Eligibility Criteria

14 Days - 32 Weeks (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of FL
  • UFL Health and Baptist
  • Emory University
  • Indiana University
  • Wesley Medical
  • University of Louisville
  • Tufts Medical Center
  • Kings County Hospital Center
  • Duke University
  • University of Texas Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Ticarcillin-clavulanate antibiotic

Rifampin generic antibiotic

Clindamycin Generic Antibiotic

Arm Description

Cohort Gestational Age (GA) Postnatal Age (PNA) Dose <30 weeks <14 days: 75 mg/kg Q12 hrs x 6 doses <30 weeks ≥14 days-45 days 75 mg/kg Q 8 hours x 6 doses <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.

Cohort GA PNA Dose <32 weeks <14 days 10 mg/kg Q 24 hours x 4 doses <32 weeks ≥14 days-120 days 15 mg/kg Q 24 hours x 4 doses ≥32 weeks <14 days 15 mg/kg Q 24 hours x 4 doses ≥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.

Cohort GA PNA Dose <30 weeks <14 days 10 mg/kg Q 12 hours x 6 doses <30 weeks ≥14 days-45 days 10 mg/kg Q 8 hours x 6 doses <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.

Outcomes

Primary Outcome Measures

Cohort 1: Area under the curve infinity (AUCinfinity) for rifampin
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 rifampin
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 rifampin
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 rifampin
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

Cohort 1: Adverse events for participants receiving rifampin
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 rifampin
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

Full Information

First Posted
November 9, 2012
Last Updated
July 25, 2023
Sponsor
Phillip Brian Smith
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1. Study Identification

Unique Protocol Identification Number
NCT01728363
Brief Title
Pharmacokinetics (PK) of Antistaphylococcal Antibiotics in Infants (NICHD-2012-02-Staph Trio)
Acronym
Staph
Official Title
Pharmacokinetics of Antistaphylococcal Antibiotics in Infants
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Phillip Brian Smith

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Infection
Keywords
Staphylococcal

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ticarcillin-clavulanate antibiotic
Arm Type
Experimental
Arm Description
Cohort Gestational Age (GA) Postnatal Age (PNA) Dose <30 weeks <14 days: 75 mg/kg Q12 hrs x 6 doses <30 weeks ≥14 days-45 days 75 mg/kg Q 8 hours x 6 doses <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.
Arm Title
Rifampin generic antibiotic
Arm Type
Experimental
Arm Description
Cohort GA PNA Dose <32 weeks <14 days 10 mg/kg Q 24 hours x 4 doses <32 weeks ≥14 days-120 days 15 mg/kg Q 24 hours x 4 doses ≥32 weeks <14 days 15 mg/kg Q 24 hours x 4 doses ≥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.
Arm Title
Clindamycin Generic Antibiotic
Arm Type
Experimental
Arm Description
Cohort GA PNA Dose <30 weeks <14 days 10 mg/kg Q 12 hours x 6 doses <30 weeks ≥14 days-45 days 10 mg/kg Q 8 hours x 6 doses <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.
Intervention Type
Drug
Intervention Name(s)
Antibiotic
Other Intervention Name(s)
Ticarcillin-clavulanate generic; Brand Timentin, Rifampin generic; Brand Rifadin, Rimatane, Clindamycin generic; Brand Cleocin
Intervention Description
Ticarcillin-clavulanate/Timentin is an antibiotic used to treat a wide variety of bacterial infections. Rifampin/Rifadin/Rimatane is an antibiotic and first line antituberculotic. Clindamycin/Cleocin is an antibiotic used to treat a wide variety of bacterial infections and serious bacterial infections.
Primary Outcome Measure Information:
Title
Cohort 1: Area under the curve infinity (AUCinfinity) for rifampin
Description
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)
Time Frame
72 hours
Title
Cohort 1: Maximum concentration (Cmax) of rifampin
Description
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)
Time Frame
72 hours
Title
Cohort 1: Clearance (CL) of rifampin
Description
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)
Time Frame
72 hours
Title
Cohort 1: Volume of distribution at steady state (Vss) of rifampin
Description
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)
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
Cohort 1: Adverse events for participants receiving rifampin
Description
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
Time Frame
7 days after last study dose
Title
Cohort 1 participants: serious adverse events for participants receiving rifampin
Description
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
Time Frame
7 days after last study dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Days
Maximum Age & Unit of Time
32 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philip B Smith, MD
Organizational Affiliation
Duke Clinical Research Institute and DUMC
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of FL
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
UFL Health and Baptist
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Wesley Medical
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Kings County Hospital Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
University of Texas Children's Hospital
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28779462
Citation
Maharaj AR, Gonzalez D, Cohen-Wolkowiez M, Hornik CP, Edginton AN. Improving Pediatric Protein Binding Estimates: An Evaluation of alpha1-Acid Glycoprotein Maturation in Healthy and Infected Subjects. Clin Pharmacokinet. 2018 May;57(5):577-589. doi: 10.1007/s40262-017-0576-7.
Results Reference
background
PubMed Identifier
26926644
Citation
Gonzalez D, Delmore P, Bloom BT, Cotten CM, Poindexter BB, McGowan E, Shattuck K, Bradford KK, Smith PB, Cohen-Wolkowiez M, Morris M, Yin W, Benjamin DK Jr, Laughon MM. Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2888-94. doi: 10.1128/AAC.03086-15. Print 2016 May.
Results Reference
result
PubMed Identifier
30910891
Citation
Smith PB, Cotten CM, Hudak ML, Sullivan JE, Poindexter BB, Cohen-Wolkowiez M, Boakye-Agyeman F, Lewandowski A, Anand R, Benjamin DK Jr, Laughon MM; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Rifampin Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother. 2019 May 24;63(6):e00284-19. doi: 10.1128/AAC.00284-19. Print 2019 Jun.
Results Reference
result
PubMed Identifier
30710387
Citation
Watt KM, Hornik CP, Balevic SJ, Mundakel G, Cotten CM, Harper B, Benjamin DK Jr, Anand R, Laughon M, Smith PB, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Pharmacokinetics of ticarcillin-clavulanate in premature infants. Br J Clin Pharmacol. 2019 May;85(5):1021-1027. doi: 10.1111/bcp.13882. Epub 2019 Mar 6.
Results Reference
result
PubMed Identifier
28137820
Citation
Smith MJ, Gonzalez D, Goldman JL, Yogev R, Sullivan JE, Reed MD, Anand R, Martz K, Berezny K, Benjamin DK Jr, Smith PB, Cohen-Wolkowiez M, Watt K; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of Clindamycin in Obese and Nonobese Children. Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02014-16. doi: 10.1128/AAC.02014-16. Print 2017 Apr.
Results Reference
result

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

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