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OsteomyelitisPhase 1NCT03802552

Cefadroxil and Cephalexin Drug Levels and Dosing in Pediatric Musculoskeletal Infections

A Phase 1 study testing Cefadroxil and Cephalexin in people with Osteomyelitis and Septic Arthritis, run by University of Colorado, Denver at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months to 18 years
Conditions the study is for
Osteomyelitis, Septic Arthritis, Pyomyositis
What is being tested?
Cefadroxil and Cephalexin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
1 May 2019to 30 Apr 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 11Show fewer
  • Have a history of significant drug allergy to any beta-lactam antibiotic (e.g. anaphylaxis and/or angioedema)
  • Are on an oral cephalosporin at time of enrollment
  • Are started on an oral cephalosporin during the study
  • o Note: If an enrolled patient is started on an oral cephalosporin prior to completion of the study, they will be removed from the study. However, data obtained prior to their receipt of an oral cephalosporin will still be included in the analysis.
  • Are known to be pregnant

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Children's Hospital Colorado

    Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: Comparative Pharmacokinetics and Pharmacodynamics (PK/PD) of Cefadroxil and Cephalexin for Pediatric Musculoskeletal (MSK) Infections

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.

Read the detailed description

This study aims to shift the current treatment paradigm for the use of oral first-generation cephalosporins in pediatric musculoskeletal (MSK) infections. Optimizing treatment for MSK infections is particularly important, as osteomyelitis is one of the most common severe infections affecting children. Treatment for these infections has markedly improved over the last few decades, but significant morbidity is still seen, including the possibility of permanent disability due to pathologic fracture, growth arrest, and joint destruction. To avoid these long term sequelae and recrudescent infection, early diagnosis, appropriate therapy, and prolonged treatment courses (typically 4-6 weeks, or longer) are essential.

The most commonly used antibiotic for MSK infections is cephalexin, a first-generation cephalosporin. It is well tolerated, provides good tissue penetration, and has a preferred spectrum of activity for typical MSK pathogens, including methicillin susceptible Staphylococcus aureus (MSSA). Despite cephalexin's widespread use, its most significant disadvantage is its short plasma half-life. Because of this, cephalexin is traditionally dosed four times daily (QID) for serious infections like osteomyelitis. However, this dosing frequency, especially for prolonged treatment courses, proves difficult for both patients and their families. Concern about poor adherence drives some providers to prolong IV therapy or dose cephalexin three times daily (TID), though there are insufficient pharmacokinetic/pharmacodynamic (PK/PD) or outcome data to support TID dosing.

Cefadroxil, another first-generation cephalosporin, is an appealing alternative to cephalexin due to its longer half-life. Because of this, the investigators hypothesize that cefadroxil could be used effectively in pediatric patients with MSK infections with a more convenient dosing schedule than cephalexin. While cephalexin is typically dosed 3-4 times per day, cefadroxil could likely be dosed 2-3 times per day, even for serious infections like osteomyelitis. However, cefadroxil is rarely prescribed to children due to a lack of pediatric PK/PD data to guide dosing. Our study aims to address this unmet need and help physicians use these existing drugs in smarter and more effective ways in pediatric MSK infections.

The specific aims of this study are to:

  1. Use a Population PK approach to define comparative PK parameters of cefadroxil and cephalexin in pediatric patients with MSK infections (osteomyelitis, septic arthritis, pyomyositis).
  2. Establish reference MIC ranges for both cefadroxil and cephalexin against MSSA isolates.
  3. Perform pharmacodynamic modeling (Monte Carlo simulation) based on the above PK parameters and MIC data to evaluate the expected PK/PD target attainment of cefadroxil and cephalexin at different dosing intervals: cephalexin given as 3 vs. 4 divided doses per day; cefadroxil given as 2 vs. 3 doses against a range of MICs.

To answer these questions, patients with MSK infections admitted to Children's Hospital Colorado (CHCO) will be enrolled in this study and sequentially given doses of both cefadroxil and cephalexin. After each oral dose, serum levels of the antibiotic will be measured at set time points until the drug is expected to be fully cleared. They will then receive the second antibiotic after a 24-hour washout period. MIC ranges will be measured based on banked MSSA isolates. Based on these study-derived PK and MIC data, adequacy of the studied cephalexin and cefadroxil dosing regimens will be analyzed.

If the study is able to confirm a favorable PK/PD profile for twice daily (BID) and/or three times daily (TID) cefadroxil dosing in children, even for severe infections, it could have an immediate impact on prescribing habits. Less frequent dosing would be an improvement over the current standard of care, allowing for easier medication administration, improved adherence, and increased provider confidence for early transition to oral therapy, which are all essential for optimal treatment of pediatric MSK infections.

Being tested
Cefadroxil, Cephalexin
Medical subject headings
Osteomyelitis, Arthritis, Infectious, Pyomyositis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CefadroxilDrug

    Also called Duricef

    oral one-time dose of cefadroxil

  • CephalexinDrug

    Also called Keflex

    oral one-time dose of cephalexin

Study groups in NCT03802552
Study groupRoleWhat they receive
Cefadroxil then CephalexinExperimentalReceive cefadroxil first, then receive cephalexin after washout.
Receives: Drug: Cefadroxil; Drug: Cephalexin
Cephalexin then CefadroxilExperimentalReceive cephalexin first, then receive cefadroxil after washout.
Receives: Drug: Cefadroxil; Drug: Cephalexin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time above Minimum Inhibitory Concentration (T > MIC)

    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.

    Measured: up to 24 hours

Secondary outcomes (7)
  1. Clearance (CL/F) of cefadroxil and cephalexin

    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the Clearance, or CL/F (L/h/kg), of both drugs.

    Measured: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

  2. Volume of Distribution (V/F) of cefadroxil and cephalexin

    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.

    Measured: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

  3. Half life (T1/2) of cefadroxil and cephalexin

    In defining pharmacokinetic parameters for both cephalexin and cefadroxil, the investigators will assess the half life, or T1/2 (hours), of both drugs.

    Measured: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

  4. Area under the curve (AUC) of cefadroxil and cephalexin

    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.

    Measured: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

  5. Peak serum drug concentration (Cmax) of cefadroxil and cephalexin

    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.

    Measured: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

  6. Minimum serum drug concentration (Cmin) of cefadroxil and cephalexin

    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.

    Measured: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

  7. Time at which maximal drug concentration is achieved (Tmax) of cefadroxil and cephalexin

    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.

    Measured: Serum drug levels obtained at: 1, 2, 6, 8 hours (cephalexin); and 1, 2, 6, 8, 12 hours (cefadroxil)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2019
  2. Study start1 May 2019
  3. Primary completion30 Apr 2021
  4. Study completion30 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03802552
Sponsor's protocol ID
18-2142
Status last verified
May 2021
First submitted
26 Dec 2018
Last updated
2 Jun 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cefadroxil and Cephalexin in people with Osteomyelitis and Septic Arthritis, run by University of Colorado, Denver at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time above Minimum Inhibitory Concentration (T > MIC) (time frame: up to 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.

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