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