Persistent Methicillin Resistant Staphylococcus Aureus Eradication Protocol (PMEP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Johns Hopkins University
Sponsor:
Collaborators:
Case Western Reserve University
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Michael Boyle, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01594827
First received: May 7, 2012
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Drug: 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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Persistent MRSA Eradication Protocol (PMEP)

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Percentage 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 ] [ Designated as safety issue: No ]
    The hypothesis for our primary outcome is that the aggressive treatment arm will result in significantly greater eradication of persistent MRSA from the respiratory tract of CF adolescents and adults on day 58 (1 month after completion of therapy) compared to the placebo/standard treatment arm. Our primary outcome will be comparing the proportion of CF patients in the treatment arm who have a negative induced sputum MRSA culture at Day 58 to the proportion of patients in the placebo arm who have a negative induced sputum MRSA culture at Day 58.


Secondary Outcome Measures:
  • Percentage of patients MRSA free by induced sputum respiratory tract culture [ Time Frame: Days 29 and 118 ] [ Designated as safety issue: No ]
    Percentage of patients MRSA free by induced sputum respiratory tract culture one day after completion of four-week eradication protocol (Day 29) and 3 months after completion of intervention (Day 118) in intervention arm vs standard treatment arm

  • Change in FEV1% predicted from baseline [ Time Frame: Days 29, 58, and 118 ] [ Designated as safety issue: No ]
    Change in FEV1% predicted from baseline at Days 29, 58, and 118 in treatment vs. standard care group

  • Time to First CF Exacerbation [ Time Frame: Day 1 to Day 118 ] [ Designated as safety issue: No ]
    Time to First CF Exacerbation using a standardized exacerbation definition from Day 1 to Day 118

  • Total Number of Pulmonary Exacerbations [ Time Frame: Days 58 and 118 ] [ Designated as safety issue: No ]
    Total Number of Pulmonary Exacerbations using a standardized exacerbation definition at Days 58 and Days 118 in treatment vs. standard care group

  • Change if FEV1% Predicted from Screening [ Time Frame: Days 29, 58, and 118 ] [ Designated as safety issue: No ]
    Change in FEV1% predicted from Screening at Days 29, 58, and 118 in treatment vs. standard care group

  • Change in Patient Reported Quality of Life (CFQ-R)(respiratory) [ Time Frame: Days 14, 29, 58 and 118 ] [ Designated as safety issue: No ]
    Change in Patient Reported Quality of Life (CFQ-R)(respiratory)from baseline to Days 14, 29,58, and 118

  • Development of Antibiotic Resistance [ Time Frame: Day 58 (Visit 5) ] [ Designated as safety issue: No ]
    Number of patients with newly developed MRSA resistance to vancomycin, TMP/SMX, doxycycline, or rifampin.


Estimated Enrollment: 40
Study Start Date: October 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inhaled Vancomycin and Oral Antibiotics
In the experimental arm CF participants are randomized to 28 days of inhaled sterile vancomycin (250 mg twice a day) as well as 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP-SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
Drug: Inhaled Vancomycin
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.
Drug: Rifampin

Oral Rifampin by mouth for 28 days

  1. >45 kg: 600 mg by mouth daily
  2. 35-45 kg : 450 mg by mouth daily
  3. 25-34.9 kg: 300 mg by mouth daily
Other Name: Rifadin
Drug: Trimethoprim/Sulfamethoxazole (TMP/SMX)

Oral trimethoprim/sulfamethoxazole (DS-160/800)

  1. >45 kg: two DS tablets twice a day by mouth (320/1600)
  2. 25-45 kg: one DS tablet twice a day by mouth (160/800)
Other Names:
  • Bactrim
  • Septra
Drug: Doxycycline

If sulfa intolerant or TMP/SMX Resistant, use instead oral doxycycline

  1. >45 kg: 100 mg by mouth twice a day
  2. 35-45 kg : 75 mg by mouth twice a day iii. 25-34.9 kg: 50 mg by mouth twice a day
Other Names:
  • Vibramycin
  • Adoxa
Drug: Mupirocin Nasal Ointment
Mupirocin 2% intranasal ointment: half of single use tube applied into each nostril twice a day for 5 days.
Other Name: Bactroban
Drug: 4% chlorhexidine gluconate liquid skin cleanser
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.
Other Name: Hibiclens
Active Comparator: Inhaled Placebo (Sterile Water) and Oral Antibiotics
In the active comparator arm CF participants are randomized to 28 days of inhaled sterile placebo (saline) and are treated with 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP-SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
Drug: Placebo (Sterile Water)
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.
Drug: Rifampin

Oral Rifampin by mouth for 28 days

  1. >45 kg: 600 mg by mouth daily
  2. 35-45 kg : 450 mg by mouth daily
  3. 25-34.9 kg: 300 mg by mouth daily
Other Name: Rifadin
Drug: Trimethoprim/Sulfamethoxazole (TMP/SMX)

Oral trimethoprim/sulfamethoxazole (DS-160/800)

  1. >45 kg: two DS tablets twice a day by mouth (320/1600)
  2. 25-45 kg: one DS tablet twice a day by mouth (160/800)
Other Names:
  • Bactrim
  • Septra
Drug: Doxycycline

If sulfa intolerant or TMP/SMX Resistant, use instead oral doxycycline

  1. >45 kg: 100 mg by mouth twice a day
  2. 35-45 kg : 75 mg by mouth twice a day iii. 25-34.9 kg: 50 mg by mouth twice a day
Other Names:
  • Vibramycin
  • Adoxa
Drug: Mupirocin Nasal Ointment
Mupirocin 2% intranasal ointment: half of single use tube applied into each nostril twice a day for 5 days.
Other Name: Bactroban
Drug: 4% chlorhexidine gluconate liquid skin cleanser
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.
Other Name: Hibiclens

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

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594827

Contacts
Contact: Karen A Callahan, RN, MS, CCRP 443-287-8983 kcallah1@jhmi.edu
Contact: David Weaver, BSN, RN 216-844-3267 david.weaver@uhhospitals.org

Locations
United States, Maryland
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21205
Contact: Erin Felling, BSN, RN    410-955-1167    efellin1@jhmi.edu   
Contact: Karen Callahan, BSN, RN    410-955-1167    kcallah1@jhmi.edu   
Principal Investigator: Michael P Boyle, M.D.         
United States, Ohio
Rainbow Babies and Children's Hospital Recruiting
Cleveland, Ohio, United States, 44106
Contact: David Weaver, BSN RN    216-844-3267    david.weaver@uhhospitals.org   
Contact: Elliott Dasenbrook, MD, MHS    216-844-3267    ecd28@case.edu   
Principal Investigator: Elliott Dasenbrook, M.D, MHS         
Sponsors and Collaborators
Michael Boyle
Case Western Reserve University
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Michael P Boyle, MD Johns Hopkins School of Medicine
Principal Investigator: Elliott Dasenbrook, MD, MHS Case Western University
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael Boyle, Associate Professor of Medicine, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01594827     History of Changes
Other Study ID Numbers: PMEP
Study First Received: May 7, 2012
Last Updated: March 11, 2014
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Methicillin-resistant Staphylococcus aureus
Vancomycin

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Staphylococcal Infections
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Doxycycline
Methicillin
Rifampin
Vancomycin
Mupirocin
Chlorhexidine
Chlorhexidine gluconate
Sulfamethoxazole
Trimethoprim
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Local
Disinfectants
Dermatologic Agents
Antimalarials
Antiprotozoal Agents

ClinicalTrials.gov processed this record on August 18, 2014