Persistent Methicillin Resistant Staphylococcus Aureus Eradication Protocol (PMEP)
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis
Intervention: Inhaled Vancomycin; Placebo (Sterile Water); Rifampin; Trimethoprim/Sulfamethoxazole (TMP/SMX); Doxycycline; Mupirocin Intranasal Creme; 4% chlorhexidine gluconate liquid skin cleanser
Intervention description: On Days 1-28, subjects will receive nebulized Vancomycin. This will be supplied as a 250 mg solution to be nebulized two times a day for 28 days in 5cc sterile water. Patients will use a Pari Sprint nebulizer and Pari Vios compressor as the delivery system.; On Days 1-28, subjects will receive 5cc of a nebulized Placebo (Sterile water) twice a day. This is a taste (quinine 0.1mg/mL) matched nebulized placebo (sterile water). Patients will use a Pari Sprint nebulizer and Pari Vios compressor as the delivery system.; Oral Rifampin by mouth for 28 days
>45 kg: 600 mg by mouth daily
35-45 kg : 450 mg by mouth daily
25-34.9 kg: 300 mg by mouth daily; Oral trimethoprim/sulfamethoxazole (DS-160/800)
>45 kg: two DS tablets twice a day by mouth (320/1600)
25-45 kg: one DS tablet twice a day by mouth (160/800); If sulfa intolerant or TMP/SMX Resistant, use instead oral doxycycline
>45 kg: 100 mg by mouth twice a day
35-45 kg : 75 mg by mouth twice a day iii. 25-34.9 kg: 50 mg by mouth twice a day; Mupirocin 2% intranasal creme: half of single use tube applied into each nostril twice a day for 5 days.; Hibiclens 15cc liquid skin cleanser packets (4% chlorhexidine gluconate): use three packets once weekly for four weeks in the shower from the neck to toes, with attention on the axilla, groin, and buttocks.
Intervention MeSH terms: Chlorhexidine; Chlorhexidine gluconate; Vancomycin; Doxycycline; Rifampin; Trimethoprim; Sulfamethoxazole; Mupirocin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 29.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Methicillin-resistant Staphylococcus aureus; Vancomycin

Summary:

      The prevalence of methicillin resistant Staphylococcus aureus (MRSA) respiratory infection in
      Cystic Fibrosis (CF) has increased dramatically over the last decade. Evidence suggests that
      persistent infection with MRSA may result in an increased rate of decline in Forced
      Expiratory Volume (FEV)1 and shortened survival. Currently there are no conclusive studies
      demonstrating an effective aggressive treatment protocol for persistent MRSA respiratory
      infection in CF. Data demonstrating an effective and safe method of clearing persistent MRSA
      infection are needed.

      The purpose of this study is to evaluate the safety and efficacy of a 28-day course of
      vancomycin for inhalation, 250 mg twice a day, (in combination with oral antibiotics) in
      eliminating MRSA from the respiratory tract of individuals with CF and persistent MRSA
      infection. Subjects will be assigned in a 1:1 ratio to either vancomycin for inhalation (250
      mg twice a day) or taste matched placebo and will be followed for 3 additional months. In
      addition, both groups will receive oral rifampin, a second oral antibiotic (TMP-SMX or
      doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes.
      Forty patients with persistent respiratory tract MRSA infection will be enrolled in this
      trial.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female ≥ 12 years of age.

          2. Confirmed diagnosis of CF based on the following criteria:

             positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis) and/or a
             genotype with two identifiable mutations consistent with CF or abnormal Nasal
             Potential Difference (NPD), and one or more clinical features consistent with the CF
             phenotype.

          3. 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.

          4. Two positive MRSA respiratory cultures in the last two years at least six months
             apart, plus a positive MRSA respiratory culture at Screening Visit and Run-in (Day
             -14) Visit.

          5. At least 50% of respiratory cultures from the time of the first MRSA culture (in the
             last two years) have been positive for MRSA.

          6. Forced Expiratory Volume (FEV)1 > 40% of predicted normal for age, gender, and height
             at Screening, for subjects 18 years of age or older..

          7. FEV1> 60% of predicted normal for age, gender, and height at Screening, for subjects
             12--17 years of old.

          8. Females of childbearing potential must agree to practice one highly effective method
             of birth control, including abstinence. Note: highly effective methods of birth
             control are those, alone or in combination, that result in a failure rate less than 1%
             per year when used consistently and correctly. Female patients who utilize hormonal
             contraceptives as a birth control method must have used the same method for at least 3
             months before study dosing. If the patient is using a hormonal form of contraception,
             patients will be required to also use barrier contraceptives as rifampin can affect
             the reliability of hormone therapy. Barrier contraceptives such as male condom or
             diaphragm are acceptable if used in combination with spermicides

        Exclusion Criteria:

          1. An acute upper or lower respiratory infection, pulmonary exacerbation, or change in
             routine therapy (including antibiotics) for pulmonary disease within 42 days of the
             Day 1 Visit (2 weeks prior to Screening visit).

          2. Individuals on chronic continuous inhaled antibiotics without interruption who are not
             willing to substitute vancomycin or placebo for their scheduled inhaled antibiotic
             during days 0-28 of the study (every other month inhaled antibiotics are acceptable)

          3. Use of oral or inhaled anti-MRSA drugs within two weeks of the Screening Visit.

          4. History of intolerance to inhaled vancomycin or inhaled albuterol.

          5. History of intolerance to rifampin or both TMP/SMX and doxycycline.

          6. Resistance to rifampin or both TMP/SMX and doxycycline at Screening.

          7. Resistance to vancomycin at Screening.

          8. Abnormal renal function, defined as creatinine clearance < 50 mL/min using the
             Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening.

          9. Abnormal liver function, defined as ≥ 3x upper limit of normal (ULN), of serum
             aspartate transaminase (AST) or serum alanine transaminase (ALT), or known cirrhosis.
             at the time of Screening.

         10. Serum hematology or chemistry results which in the judgment of the investigator would
             interfere with completion of the study.

         11. History of or listed for solid organ or hematological transplantation

         12. History of sputum culture with non-tuberculous Mycobacteria in the last 6 months.

         13. History of sputum culture with Burkholderia Cepacia in the last year.

         14. Planned continuous use of soft contact lenses while taking rifampin and no access to
             glasses.

         15. Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg
             prednisone a day or 20 mg prednisone every other day

         16. Administration of any investigational drug or device within 28 days of Screening or
             within 6 half-lives of the investigational drug (whichever is longer).

         17. Patients on inhaled antibiotics must have been on the same regimen for the 4 months
             prior to screening

         18. Female patients of childbearing potential who are pregnant or lactating, or plan on
             becoming pregnant

         19. Any serious or active medical or psychiatric illness, which in the opinion of the
             investigator, would interfere with patient treatment, assessment, or adherence to the
             protocol.