Early Methicillin-resistant Staphylococcus Aureus (MRSA) Therapy in Cystic Fibrosis (CF)

• Status: Terminated
• Trial end date: 2015-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Purpose: There has been a recent, rapid increase in prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) among patients with Cystic Fibrosis (22% across US CF centers in 2009). Some epidemiologic studies suggest possible worse outcomes, a recent analyses showing this with chronic but not intermittent MRSA. Given the chronic difficult to treat lung infections in CF it is unclear how the onset of MRSA should be approached. This randomized, controlled, interventional study seeks to determine if an early eradication protocol is effective for eradication of MRSA and will provide an opportunity to obtain data regarding early clinical impact of new isolation of MRSA.

Participants: Cystic fibrosis patients with new isolation of MRSA from their respiratory culture on a routine clinic visit.

Procedures (methods): Randomized, open-label, multi-center study comparing use of an eradication protocol to an observational group who receives the current standard of care i.e. treatment for MRSA only with pulmonary exacerbations.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Baylor College of Medicine; CF Therapeutics Development Network Coordinating Center; Children's Hospital Medical Center, Cincinnati; Cook Children's Medical Center; Seattle Children's Hospital; St. Louis Children's Hospital; University of Alabama at Birmingham; University of Colorado, Denver; University of Florida; University of Michigan; University of Texas Southwestern Medical Center; University of Washington; Washington University School of Medicine
• Treatments: Chlorhexidine; Chlorhexidine gluconate; Minocycline; Mupirocin; Rifampin; Sulfamethoxazole; Trimethoprim

Criteria

Inclusion Criteria:

1. Male or female ≥ 4 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:

• sweat chloride ≥ 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)

• two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene

• Abnormal nasal potential difference (change in NPD in response to a low chloride solution and isoproteronol of less than -5 mV)

3. First OR early repeat MRSA colonization defined as:

• First MRSA colonization: first documented isolation of MRSA from respiratory tract occurred ≤ 6 months prior to screening

• OR Early repeat MRSA colonization:

MRSA was previously isolated from the respiratory tract (≤ 2 times), but this was followed by at least 1 year of documented negative cultures for MRSA as noted below:

-- At least 2 cultures performed at least 3 months apart to document 1 year of culture negativity. Each of these cultures should be documented to have been collected at least 1 week after end of any antibiotic prescription with MRSA activity.

Patient again recently positive for MRSA from the respiratory tract (within 6 months prior to screening)

4. Clinically stable with no significant changes in health status within the 14 days prior to screening

5. 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

A repeat culture from the respiratory tract is obtained at screening but does not have to be positive to be able to enter the study.

Exclusion Criteria:

1. Received antibiotics with activity against MRSA within 28 days prior to screening (see study manual for list of antibiotics)

2. Use of an investigational agent within 28 days prior to screening

3. For subjects ≥ 6 years of age: FEV1 at screening < 30% 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 resistant to rifampin OR resistant to both TMP/SMX and minocycline

5. History of intolerance to oral rifampin, or topical chlorhexidine or mupirocin

6. History of intolerance to both TMP/SMX and minocycline

7. < 8 years of age and either allergic or intolerant to TMP/SMX or screening MRSA resistant to TMP/SMX

8. ≥ 8 years of age and allergic or intolerant to TMP/SMX and screening MRSA resistant to minocycline

9. ≥ 8 years of age and allergic or intolerant to minocycline and screening MRSA resistant to TMP/SMX

10. For females of child bearing potential: pregnant, breastfeeding, or unwilling to use barrier contraception through Day 15 of the study

11. Abnormal renal function at Screening, defined as estimated creatinine clearance <50 mL/min using the Cockcroft-Gault equation

12. Abnormal liver function at the time of screening, defined as ≥2x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT)

13. History of solid organ or hematological transplantation

14. 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.