Treatment for early MRSA infections in cystic fibrosis patients

STaph Aureus Resistance-Treat Early and Repeat (STAR-TER)

This study is testing a new treatment with antibiotics for people with cystic fibrosis who have recently been diagnosed with MRSA to see if it helps clear the infection.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 2 Years to 45 Years
• Sex: All
• Sponsor: University of North Carolina, Chapel Hill (Academic / other)
• Locations: 9 sites (Denver, Colorado and 8 other locations)
• Trial ID: NCT03489629 on ClinicalTrials.gov

What this trial studies

This interventional trial aims to evaluate the efficacy and safety of a streamlined treatment for early onset methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis. Participants will receive a combination of oral antibiotics and nasal mupirocin over a six-month period, with assessments of MRSA culture status at various intervals. The study will enroll 42 subjects who have recently been diagnosed with MRSA, and the primary endpoint will focus on the proportion of positive MRSA respiratory cultures at Day 28. The trial will also explore the effects of a repeat treatment protocol after a wash-out period.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 2 to 45 years with a confirmed diagnosis of cystic fibrosis and recent MRSA colonization.

Not a fit: Patients who have not been recently diagnosed with MRSA or are outside the age range of 2 to 45 years may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of MRSA infections in cystic fibrosis patients, potentially leading to better respiratory health outcomes.

How similar studies have performed: Previous studies have shown promise in treating MRSA infections in cystic fibrosis patients, but this specific approach is novel.

Eligibility criteria

Inclusion Criteria:

1. Male or female ≥ 2 and ≤ 45 years of age at the Screening Visit.
2. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

   1. sweat chloride ≥ 60 milliequivalents/liter by quantitative pilocarpine iontophoresis test (QPIT)
   2. two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene
   3. abnormal nasal potential difference(NPD) (change in NPD in response to a low chloride solution and isoproteronol of less than -5 mV)
3. First OR early MRSA colonization defined as:

   1. First MRSA colonization: first documented isolation of MRSA from respiratory tract occurred ≤ 6 months prior to screening
   2. Early MRSA colonization: MRSA was previously isolated from the respiratory tract ≤ 2 times over the past 3.5 years, but this was followed by at least 1 year of documented negative cultures for MRSA
4. MRSA is available to the central laboratory - either the incident MRSA isolate from the clinic visit or the subject is MRSA positive at the screening visit
5. Clinically stable with no significant changes in health status within the 14 days prior to screening
6. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

Exclusion Criteria:

1. Received antibiotics with activity against MRSA within 28 days prior to screening
2. Use of an investigational agent within 28 days prior to screening
3. For subjects ≥ 6 years of age: FEV1 at screening \< 25% of predicted for age based on the Wang (males \< 18 years, females \< 16 years) or Hankinson (males ≥ 18 years, females ≥ 16 years) standardized equations
4. MRSA from the screening culture or the most recent clinical care visit within 6 months prior to screening resistant to TMP/SMX
5. History of intolerance to topical chlorhexidine or mupirocin
6. History of intolerance to both TMP/SMX and minocycline
7. \< 8 years of age and allergic or intolerant to TMP/SMX
8. ≥ 8 years of age and allergic or intolerant to TMP/SMX and MRSA isolate (from screening or clinical care visit)is resistant to minocycline
9. For females of child bearing potential: pregnant, breastfeeding, or unwilling to use barrier contraception through Day 42 of the study
10. Subjects with history of abnormal renal function will need screening labs showing normal function Abnormal renal function is defined as estimated creatinine clearance \<50 mL/min using the:

    1. Bedside Schwartz Equation for subjects \<18 years of age, and
    2. Levey Glomerular filtration rate (GFR) Equation for subjects ≥ 18 years of age.
11. Subjects with a history of abnormal liver function will need to have screening labs showing normal transaminases. Liver dysfunction is defined as ≥3x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT) or abnormal synthetic function
12. History of solid organ or hematological transplantation
13. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Where this trial is running

Denver, Colorado and 8 other locations

• National Jewish Health — Denver, Colorado, United States (Recruiting)
• Indiana University — Indianapolis, Indiana, United States (Recruiting)
• University of Michigan Health System — Ann Arbor, Michigan, United States (Recruiting)
• St. Louis Children's Hospital — Saint Louis, Missouri, United States (Recruiting)
• N.C. Memorial Hospital and N.C. Children's Hospital — Chapel Hill, North Carolina, United States (Recruiting)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
• Cook Children's Medical Center — Fort Worth, Texas, United States (Recruiting)
• Texas Children's Hospital, Baylor College of Medicine — Houston, Texas, United States (Recruiting)
• University of Washington Medical Center and Seattle Children's — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Marianne Muhlebach, MD — University of North Carolina, Chapel Hill
• Study coordinator: Marianne Muhlebach, MD

Conditions Cystic Fibrosis; Methicillin-resistant Staphylococcus aureus; Early infection; Treatment; Forced Expiratory Volume in 1 Second