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Cefadroxil and Cephalexin Drug Levels and Dosing in Pediatric Musculoskeletal Infections

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ClinicalTrials.gov Identifier: NCT03802552
Recruitment Status : Enrolling by invitation
First Posted : January 14, 2019
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
The goal of this study is to figure out the best doses for two antibiotics (called cefadroxil and cephalexin) when they are used to treat bone, joint, or muscle infections in children. In order to do this, the study will collect data about children admitted to Children's Hospital Colorado who have these types of infections. During the study, these patients will receive doses by mouth of each of these antibiotics, in addition to an IV antibiotic (given through a vein) used to treat their infection. After the dose of the first antibiotic, blood samples will be drawn every few hours to measure how much of the drug is still in their body, until it is all gone. After the first antibiotic is out of the patient's body, the same will be done for the second antibiotic. Measurements, in the lab, of how much of these antibiotics are needed to kill the most common bacteria causing these infections, which is a type of "Staph" bacteria called "MSSA", will be taken. Finally, the blood levels of the antibiotics and the information from the lab tests about the Staph bacteria will be used to calculate how much and how often of the antibiotic should be given to children with bone, joint, or muscle infections. Currently, these types of infections are treated with an antibiotic that children have to take four times every day. The goal of this study is to find an antibiotic that children can take only two or three times per day.

Condition or disease Intervention/treatment Phase
Osteomyelitis Septic Arthritis Pyomyositis Drug: Cefadroxil Drug: Cephalexin Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Comparative Pharmacokinetics and Pharmacodynamics (PK/PD) of Cefadroxil and Cephalexin for Pediatric Musculoskeletal (MSK) Infections
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2021


Arm Intervention/treatment
Experimental: Cefadroxil then Cephalexin
Receive cefadroxil first, then receive cephalexin after washout.
Drug: Cefadroxil
oral one-time dose of cefadroxil
Other Name: Duricef

Drug: Cephalexin
oral one-time dose of cephalexin
Other Name: Keflex

Experimental: Cephalexin then Cefadroxil
Receive cephalexin first, then receive cefadroxil after washout.
Drug: Cefadroxil
oral one-time dose of cefadroxil
Other Name: Duricef

Drug: Cephalexin
oral one-time dose of cephalexin
Other Name: Keflex




Primary Outcome Measures :
  1. Time above Minimum Inhibitory Concentration (T > MIC) [ Time Frame: up to 24 hours ]
    As a surrogate of treatment efficacy for cefadroxil and cephalexin, the investigators will measure the time that free serum concentrations (T > MIC) of cefadroxil and cephalexin remain above the minimum inhibitory concentration (MIC) of MSSA. A range of MICs will be directly measured, with an expected range from 0.125 to 4.


Secondary Outcome Measures :
  1. Clearance (CL/F) of cefadroxil and cephalexin [ Time Frame: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil) ]
    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the Clearance, or CL/F (L/h/kg), of both drugs.

  2. Volume of Distribution (V/F) of cefadroxil and cephalexin [ Time Frame: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil) ]
    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the Volume of Distribution, or V/F (L/kg), of both drugs.

  3. Half life (T1/2) of cefadroxil and cephalexin [ Time Frame: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil) ]
    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the half life, or T1/2 (hours), of both drugs.

  4. Area under the curve (AUC) of cefadroxil and cephalexin [ Time Frame: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil) ]
    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the area under the curve, or AUC (h*mg/L), of both drugs.

  5. Peak serum drug concentration (Cmax) of cefadroxil and cephalexin [ Time Frame: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil) ]
    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the peak serum drug concentration, or Cmax (mg/L), of both drugs.

  6. Minimum serum drug concentration (Cmin) of cefadroxil and cephalexin [ Time Frame: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil) ]
    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the minimum serum drug concentration, or Cmin (mg/L), of both drugs.

  7. Time at which maximal drug concentration is achieved (Tmax) of cefadroxil and cephalexin [ Time Frame: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil) ]
    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the time at which maximal drug concentration is achieved, or Tmax (hours), of both drugs.



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Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Children who are admitted to Children's Hospital Colorado and:

  • Are to be treated for a deep musculoskeletal infection (osteomyelitis, septic arthritis, pyomyositis), as determined by their primary medical team
  • Are aged 6 months to 18 years
  • Clinically likely to be admitted for 48-72 hours

Exclusion Criteria:

Patients will be excluded if they:

  • Are less than 6 months of age or greater than 18 years of age
  • Weigh less than 5.5 kg
  • Weigh greater than the 95%ile for age
  • Have underlying current renal disease based on medical history
  • Have an underlying chronic medical condition—examples include cystic fibrosis, sickle cell anemia, inflammatory bowel disease, pancreatitis, hepatitis, immunodeficiency, cancer, spina bifida, chromosomal abnormalities, cerebral palsy, or metabolic disorders.
  • Have a history of significant drug allergy to any beta-lactam antibiotic (e.g. anaphylaxis and/or angioedema)
  • Are on an oral antimicrobial at time of enrollment
  • Are started on an oral antimicrobial during the study

    o Note: If an enrolled patient is started on an oral antimicrobial prior to completion of the study, they will be removed from the study. However, data obtained prior to their receipt of an oral antimicrobial will still be included in the analysis.

  • Are planned to be discharged within 48 hours
  • Are known to be pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03802552


Locations
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United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Andrew Haynes, MD University of Colorado, Denver

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03802552     History of Changes
Other Study ID Numbers: 18-2142
First Posted: January 14, 2019    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Osteomyelitis
Arthritis, Infectious
Pyomyositis
Infection
Arthritis
Joint Diseases
Musculoskeletal Diseases
Bone Diseases, Infectious
Bone Diseases
Suppuration
Myositis
Muscular Diseases
Neuromuscular Diseases
Nervous System Diseases
Cephalexin
Cefadroxil
Anti-Bacterial Agents
Anti-Infective Agents