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

• ClinicalTrials.gov Identifier: NCT01728363
• Recruitment Status: Completed
• First Posted: November 19, 2012
• Last Update Posted: January 21, 2020
• Sponsor: Phillip Brian Smith
• Information provided by (Responsible Party): Phillip Brian Smith, Duke University

Study Description

Brief Summary:

Multiple center, open-label, PK study

Condition or disease	Intervention/treatment	Phase
Systemic Infection	Drug: Antibiotic	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 63 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetics of Antistaphylococcal Antibiotics in Infants
• Study Start Date: January 2013
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ticarcillin-clavulanate antibiotic; 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.	Drug: Antibiotic; 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.; Other Names: Ticarcillin-clavulanate generic; Brand Timentin; Rifampin generic; Brand Rifadin, Rimatane; Clindamycin generic; Brand Cleocin
Experimental: Rifampin generic antibiotic; 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.	Drug: Antibiotic; 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.; Other Names: Ticarcillin-clavulanate generic; Brand Timentin; Rifampin generic; Brand Rifadin, Rimatane; Clindamycin generic; Brand Cleocin
Experimental: Clindamycin Generic Antibiotic; 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.	Drug: Antibiotic; 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.; Other Names: Ticarcillin-clavulanate generic; Brand Timentin; Rifampin generic; Brand Rifadin, Rimatane; Clindamycin generic; Brand Cleocin

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetic concentrations in plasma will be measured at a central lab using a validated bioanalytical assay. Plasma samples will be drawn according to specific schedules for each drug [ Time Frame: 24 hours ]
   to determine the Pharmacokinetics of rifampin, ticarcillin-clavulanate, and clindamycin

Secondary Outcome Measures :

1. Safety review will be performed through monitoring of adverse events each day that the infant is on study [ Time Frame: 7 days after last study dose ]
   adverse events, serious adverse events, serious suspected adverse reactions, serious adverse reactions, suspected adverse reaction, adverse reactions will be assessed.

Eligibility Criteria

• Ages Eligible for Study: up to 32 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

University of FL

Gainesville, Florida, United States, 32610

UFL Health and Baptist

Jacksonville, Florida, United States, 32209

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Kansas

Wesley Medical

Wichita, Kansas, United States, 67214

United States, Kentucky

University of Louisville

Louisville, Kentucky, United States, 40202

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

United States, New York

Kings County Hospital Center

Brooklyn, New York, United States, 11203

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27705

United States, Texas

University of Texas Children's Hospital

Galveston, Texas, United States, 77555

Sponsors and Collaborators

Phillip Brian Smith

Investigators

• Principal Investigator: Philip B Smith, MD; Duke Clinical Research Institute and DUMC

More Information

Publications of Results:

Gonzalez D, Melloni C, Yogev R, Poindexter BB, Mendley SR, Delmore P, Sullivan JE, Autmizguine J, Lewandowski A, Harper B, Watt KM, Lewis KC, Capparelli EV, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act - Pediatric Trials Network Administrative Core Committee. Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. Clin Pharmacol Ther. 2014 Oct;96(4):429-37. doi: 10.1038/clpt.2014.134. Epub 2014 Jun 20.

Ericson JE, Arnold C, Cheeseman J, Cho J, Kaneko S, Wilson E, Clark RH, Benjamin DK Jr, Chu V, Smith PB, Hornik CP; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee. Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants. J Pediatr Gastroenterol Nutr. 2015 Sep;61(3):334-9. doi: 10.1097/MPG.0000000000000792.

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.

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). pii: e00284-19. doi: 10.1128/AAC.00284-19. Print 2019 Jun.

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.

Maharaj AR, Gonzalez D, Cohen-Wolkowiez M, Hornik CP, Edginton AN. Improving Pediatric Protein Binding Estimates: An Evaluation of α1-Acid Glycoprotein Maturation in Healthy and Infected Subjects. Clin Pharmacokinet. 2018 May;57(5):577-589. doi: 10.1007/s40262-017-0576-7.

• Responsible Party: Phillip Brian Smith, Principal Investigator, Duke University
• ClinicalTrials.gov Identifier: NCT01728363
• Other Study ID Numbers: Pro00037820
• First Posted: November 19, 2012
• Last Update Posted: January 21, 2020
• Last Verified: January 2020

Keywords provided by Phillip Brian Smith, Duke University:

Staphylococcal

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action; Sepsis; Infection; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Anti-Bacterial Agents; Rifampin; Clindamycin; Clavulanic Acid; Ticarcillin; Anti-Infective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Leprostatic Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; Protein Synthesis Inhibitors; beta-Lactamase Inhibitors