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Persistent Methicillin Resistant Staphylococcus Aureus Eradication Protocol (PMEP)

Information source: Johns Hopkins University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Cystic Fibrosis

Intervention: Inhaled Vancomycin (Drug); Placebo (Sterile Water) (Drug); Rifampin (Drug); Trimethoprim/Sulfamethoxazole (TMP/SMX) (Drug); Doxycycline (Drug); Mupirocin Nasal Ointment (Drug); 4% chlorhexidine gluconate liquid skin cleanser (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Michael Boyle

Official(s) and/or principal investigator(s):
Michael P Boyle, MD, Principal Investigator, Affiliation: Johns Hopkins School of Medicine
Elliott Dasenbrook, MD, MHS, Principal Investigator, Affiliation: Case Western University

Overall contact:
Mary Rykiel, Phone: 410-614-1409, Email: mrykiel1@jhmi.edu


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 FEV1 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.

Clinical Details

Official title: Persistent MRSA Eradication Protocol (PMEP)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Percentage of patients MRSA free by induced sputum respiratory tract culture

Secondary outcome:

Percentage of patients MRSA free by induced sputum respiratory tract culture

Change in FEV1% predicted from baseline

Time to First CF Exacerbation

Total Number of Pulmonary Exacerbations

Change if FEV1% Predicted from Screening

Change in Patient Reported Quality of Life (CFQ-R)(respiratory)

Development of Antibiotic Resistance

Time to first anti-MRSA antibiotics (after treatment period)

Detailed description: Primary Objectives The primary objectives of this trial are to: 1. Determine the efficacy of an aggressive treatment protocol in eradicating persistent MRSA infection in individuals with CF. 2. Determine the safety of an aggressive treatment protocol in eradicating persistent MRSA infection in individuals with CF. Secondary Objectives The secondary objectives of this trial are to: 1. Determine the efficacy of an aggressive treatment protocol in improving FEV1, time to exacerbation, and quality of life in individuals with CF and persistent MRSA infection. 2. Determine if there is benefit to adding nebulized vancomycin to an aggressive oral antibiotic treatment protocol in eradicating persistent MRSA infection in individuals with CF.


Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.


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 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. FEV1 > 30% of predicted normal for age, gender, and height at Screening. 7. 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. Taking voriconazole and unable to discontinue its use from Run-in Visit to Day 29 End of Treatment Visit. 17. Administration of any investigational drug or device within 28 days of Screening or within 6 half-lives of the investigational drug (whichever is longer). 18. Patients on inhaled antibiotics must have been on the same regimen for the 4 months prior to screening 19. Female patients of childbearing potential who are pregnant or lactating, or plan on becoming pregnant 20. 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.

Locations and Contacts

Mary Rykiel, Phone: 410-614-1409, Email: mrykiel1@jhmi.edu

Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States; Recruiting
Mary Rykiel, BSN, RN, Phone: 410-614-1409, Email: mrykiel1@jhmi.edu
Kathie Deinlein, Phone: 410-502-7044, Email: kbukowsk@jhmi.edu
Michael P Boyle, M.D., Principal Investigator

Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, United States; Recruiting
David Weaver, BSN RN, Phone: 216-844-3267, Email: david.weaver@uhhospitals.org
Elliott Dasenbrook, MD, MHS, Phone: 216-844-3267, Email: ecd28@case.edu
Elliott Dasenbrook, M.D, MHS, Principal Investigator

Additional Information

Cystic Fibrosis Foundation website

Johns Hopkins Cystic Fibrosis Center website

Related publications:

Dasenbrook EC, Checkley W, Merlo CA, Konstan MW, Lechtzin N, Boyle MP. Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis. JAMA. 2010 Jun 16;303(23):2386-92. doi: 10.1001/jama.2010.791.

Dasenbrook EC, Merlo CA, Diener-West M, Lechtzin N, Boyle MP. Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis. Am J Respir Crit Care Med. 2008 Oct 15;178(8):814-21. doi: 10.1164/rccm.200802-327OC. Epub 2008 Jul 31.

Jennings MT, Boyle MP, Weaver D, Callahan KA, Dasenbrook EC. Eradication strategy for persistent methicillin-resistant Staphylococcus aureus infection in individuals with cystic fibrosis--the PMEP trial: study protocol for a randomized controlled trial. Trials. 2014 Jun 12;15:223. doi: 10.1186/1745-6215-15-223.

Starting date: October 2012
Last updated: March 30, 2015

Page last updated: August 23, 2015

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