Persistent Methicillin Resistant Staphylococcus Aureus Eradication Protocol (PMEP)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01594827
• Date of registration: 07/05/2012
• Prospective Registration: Yes
• Primary sponsor: Johns Hopkins University
• Public title: Persistent Methicillin Resistant Staphylococcus Aureus Eradication Protocol (PMEP) PMEP
• Scientific title: Persistent MRSA Eradication Protocol (PMEP)
• Date of first enrolment: October 2012
• Target sample size: 29
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01594827
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: James Chmiel, MD
• Affiliation: Case Western University

• Name: Michael P Boyle, MD
• Affiliation: Johns Hopkins School of Medicine

Key inclusion & exclusion 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.



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Placebo (Sterile Water)

Drug: Trimethoprim/Sulfamethoxazole (TMP/SMX)

Drug: Doxycycline

Drug: 4% chlorhexidine gluconate liquid skin cleanser

Drug: Inhaled Vancomycin

Drug: Mupirocin Intranasal Creme

Drug: Rifampin

Primary Outcome(s)

Number of Patients MRSA Free by Induced Sputum Respiratory Tract Culture [Time Frame: Day 58 (Visit 5), approximately 1 month after completion of the MRSA treatment protocol]

Secondary Outcome(s)

Change if FEV1% Predicted From Screening [Time Frame: Days 29, 58, and 118]

Time to First CF Exacerbation [Time Frame: Day 1 to Day 118]

Time to First Anti-MRSA Antibiotics (After Treatment Period) [Time Frame: Completion of Study Drug to Day 118]

Total Number of Pulmonary Exacerbations [Time Frame: Days 58 and 118]

Change in Forced Expiratory Volume (FEV1)% Predicted From Baseline to Day 58 [Time Frame: Baseline, Day 58]

Development of Antibiotic Resistance [Time Frame: Day 58 (Visit 5)]

Change in Patient Reported Quality of Life (CFQ-R)(Respiratory) [Time Frame: Days 29 and 58]

Percentage of Patients MRSA Free by Induced Sputum Respiratory Tract Culture [Time Frame: Day 29]

Secondary ID(s)

NA_00017536

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Cystic Fibrosis Foundation

Case Western Reserve University

Results

• Results available: Yes
• Date Posted: 20/11/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01594827