Persistent Methicillin Resistant Staphylococcus Aureus Eradication Protocol (PMEP)

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01594827
• Collaborator: Case Western Reserve University (Other), Cystic Fibrosis Foundation (Other)
• Enrollment: 29
• Locations: 2
• Arms: 2
• Actual Duration (Months): 62.9
• Patients Per Site: 14.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Inhaled Vancomycin; Drug: Placebo (Sterile Water); Drug: Rifampin; Drug: Trimethoprim/Sulfamethoxazole (TMP/SMX); Drug: Doxycycline; Drug: Mupirocin Intranasal Creme; Drug: 4% chlorhexidine gluconate liquid skin cleanser	Phase 2

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 Forced Expiratory Volume (FEV)1, 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Persistent MRSA Eradication Protocol (PMEP)
• Actual Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Dec 30, 2017
• Actual Study Completion Date: Dec 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inhaled Vanc and Oral Abx 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.; Other Names: Vanc ; Drug: Rifampin; 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; Other Names: Rifadin ; Drug: Trimethoprim/Sulfamethoxazole (TMP/SMX); 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); Other Names: Bactrim Septra ; Drug: Doxycycline; 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; Other Names: Vibramycin Adoxa ; Drug: Mupirocin Intranasal Creme; Mupirocin 2% intranasal creme: half of single use tube applied into each nostril twice a day for 5 days.; Other Names: 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 Names: Hibiclens
Active Comparator: Inhaled Placebo and Oral Abx 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.; Other Names: Placebo ; Drug: Rifampin; 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; Other Names: Rifadin ; Drug: Trimethoprim/Sulfamethoxazole (TMP/SMX); 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); Other Names: Bactrim Septra ; Drug: Doxycycline; 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; Other Names: Vibramycin Adoxa ; Drug: Mupirocin Intranasal Creme; Mupirocin 2% intranasal creme: half of single use tube applied into each nostril twice a day for 5 days.; Other Names: 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 Names: Hibiclens

Outcome Measures

Primary Outcome Measures

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

   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

1. Percentage of Patients MRSA Free by Induced Sputum Respiratory Tract Culture [Day 29]

   Percentage of patients MRSA free by induced sputum respiratory tract culture one day after completion of four-week eradication protocol (Day 29) in intervention arm vs standard treatment arm

2. Change in Forced Expiratory Volume (FEV1)% Predicted From Baseline to Day 58 [Baseline, Day 58]

   Change in Forced Expiratory Volume (FEV1)% predicted from baseline to day number 58

3. Time to First CF Exacerbation [Day 1 to Day 118]

   Time to First CF Exacerbation using a standardized exacerbation definition from Day 1 to Day 118

4. Total Number of Pulmonary Exacerbations [Days 58 and 118]

   Total Number of Pulmonary Exacerbations using a standardized exacerbation definition at Days 58 and Days 118 in treatment vs. standard care group

5. Change if FEV1% Predicted From Screening [Days 29, 58, and 118]

   Change in FEV1% predicted from Screening at Days 29, 58, and 118 in treatment vs. standard care group

6. Change in Patient Reported Quality of Life (CFQ-R)(Respiratory) [Days 29 and 58]

   Change in Patient Reported Quality of Life (CFQ-R)(respiratory) from baseline to Days 29 and 58. CFQ-R stands for Cystic Fibrosis Quality of Life Measure, Respiratory Domain. Overall range of absolute score 0 to +80. Higher score means better quality of life. Positive change in score means improvement in quality of life. Minimally clinically significant difference: +/- 4.0 units.

7. Development of Antibiotic Resistance [Day 58 (Visit 5)]

   Number of patients with newly developed MRSA resistance to vancomycin, TMP/SMX, doxycycline, or rifampin.

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

   Time between completion of Study Drug and need for anti-MRSA antibiotics to control or treat symptoms

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

2. 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.

3. At least 50% of respiratory cultures from the time of the first MRSA culture (in the last two years) have been positive for MRSA.

4. Forced Expiratory Volume (FEV)1 > 40% of predicted normal for age, gender, and height at Screening, for subjects 18 years of age or older..

5. FEV1> 60% of predicted normal for age, gender, and height at Screening, for subjects 12--17 years of old.

6. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21205
2	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• Johns Hopkins University
• Case Western Reserve University
• Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Michael P Boyle, MD, Johns Hopkins School of Medicine
• Principal Investigator: James Chmiel, MD, Case Western University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 25, 2015

More Information

Additional Information:

• Cystic Fibrosis Foundation website
• Johns Hopkins Cystic Fibrosis Center website

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.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01594827
• Other Study ID Numbers: NA_00017536
• First Posted: May 9, 2012
• Last Update Posted: Feb 26, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Johns Hopkins University: Methicillin-resistant Staphylococcus aureus; Vancomycin
• Additional relevant MeSH terms: Cystic Fibrosis; Chlorhexidine; Chlorhexidine gluconate; Vancomycin; Doxycycline; Rifampin; Trimethoprim; Sulfamethoxazole; Mupirocin

Study Results

Participant Flow

Recruitment Details	The Persistent MRSA Eradication Protocol (PMEP) was a double-blind, randomized, placebo-controlled study performed at two CF centers (Johns Hopkins Hospital, Baltimore, MD; and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, Ohio.) The study was conducted from October 2012 through March 2017.
Pre-assignment Detail	After qualifying for and enrolling in the study based on inclusion criteria, participants were required to again demonstrate MRSA positive respiratory culture at the run-in visit (day -14) in order to be randomized to treatment arms. 39 participants were assessed for eligibility but only 29 matched inclusion criteria and were randomized.

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	In the experimental arm CF participants were 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 were followed for 3 months after completion of the treatment protocol.	In the active comparator arm CF participants were randomized to 28 days of inhaled sterile placebo (saline) and 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 were followed for 3 months after completion of the treatment protocol.
Period Title: Overall Study
STARTED	14	15
COMPLETED	10	15
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	14	15	29
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	25.5	25.0	25.0
Sex: Female, Male (Count of Participants)
Female	6 42.9%	8 53.3%	14 48.3%
Male	8 57.1%	7 46.7%	15 51.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	14 100%	15 100%	29 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 13.3%	2 6.9%
White	14 100%	13 86.7%	27 93.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%	15 100%	29 100%
MRSA positive at baseline (Count of Participants)
Count of Participants [Participants]	14 100%	14 93.3%	28 96.6%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	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.	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.
Measure Participants	10	15
Count of Participants [Participants]	2 14.3%	3 20%

2. Secondary Outcome

Title	Percentage of Patients MRSA Free by Induced Sputum Respiratory Tract Culture
Description	Percentage of patients MRSA free by induced sputum respiratory tract culture one day after completion of four-week eradication protocol (Day 29) in intervention arm vs standard treatment arm
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	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.	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.
Measure Participants	10	15
Count of Participants [Participants]	5 35.7%	6 40%

3. Secondary Outcome

Title	Change in Forced Expiratory Volume (FEV1)% Predicted From Baseline to Day 58
Description	Change in Forced Expiratory Volume (FEV1)% predicted from baseline to day number 58
Time Frame	Baseline, Day 58

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	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.	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.
Measure Participants	10	15
Median (Inter-Quartile Range) [% predicted FEV1]	-2.5	1.0

4. Secondary Outcome

Title	Time to First CF Exacerbation
Description	Time to First CF Exacerbation using a standardized exacerbation definition from Day 1 to Day 118
Time Frame	Day 1 to Day 118

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	In the experimental arm CF participants were 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 were followed for 3 months after completion of the treatment protocol.	In the active comparator arm CF participants were randomized to 28 days of inhaled sterile placebo (saline) and 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 were followed for 3 months after completion of the treatment protocol.
Measure Participants	10	15
Mean (Standard Deviation) [Days]	NA (NA)	68.4 (22.2)

5. Secondary Outcome

Title	Total Number of Pulmonary Exacerbations
Description	Total Number of Pulmonary Exacerbations using a standardized exacerbation definition at Days 58 and Days 118 in treatment vs. standard care group
Time Frame	Days 58 and 118

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	In the experimental arm CF participants were 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 were followed for 3 months after completion of the treatment protocol.	In the active comparator arm CF participants were randomized to 28 days of inhaled sterile placebo (saline) and 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 were followed for 3 months after completion of the treatment protocol.
Measure Participants	10	15
Day 58	0	1
Day 118	0	3

6. Secondary Outcome

Title	Change if FEV1% Predicted From Screening
Description	Change in FEV1% predicted from Screening at Days 29, 58, and 118 in treatment vs. standard care group
Time Frame	Days 29, 58, and 118

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	In the experimental arm CF participants were 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 were followed for 3 months after completion of the treatment protocol.	In the active comparator arm CF participants were randomized to 28 days of inhaled sterile placebo (saline) and 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 were followed for 3 months after completion of the treatment protocol.
Measure Participants	10	15
Day 29	0.0 (2.1)	1.1 (2.5)
Day 58	-3.0 (2.1)	1.3 (2.5)
Day 118	-2.1 (1.4)	-0.3 (2.2)

7. Secondary Outcome

Title	Change in Patient Reported Quality of Life (CFQ-R)(Respiratory)
Description	Change in Patient Reported Quality of Life (CFQ-R)(respiratory) from baseline to Days 29 and 58. CFQ-R stands for Cystic Fibrosis Quality of Life Measure, Respiratory Domain. Overall range of absolute score 0 to +80. Higher score means better quality of life. Positive change in score means improvement in quality of life. Minimally clinically significant difference: +/- 4.0 units.
Time Frame	Days 29 and 58

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	In the experimental arm CF participants were 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 were followed for 3 months after completion of the treatment protocol.	In the active comparator arm CF participants were randomized to 28 days of inhaled sterile placebo (saline) and 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 were followed for 3 months after completion of the treatment protocol.
Measure Participants	10	15
Day 29	3.3 (4.1)	11.5 (4.2)
Day 58	-4.4 (5.0)	3.2 (4.8)

8. Secondary Outcome

Title	Development of Antibiotic Resistance
Description	Number of patients with newly developed MRSA resistance to vancomycin, TMP/SMX, doxycycline, or rifampin.
Time Frame	Day 58 (Visit 5)

Outcome Measure Data

Analysis Population Description

No resistance to doxycycline or TMP/SMX. All developed resistance was to rifampin.

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	In the experimental arm CF participants were 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 were followed for 3 months after completion of the treatment protocol.	In the active comparator arm CF participants were randomized to 28 days of inhaled sterile placebo (saline) and 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 were followed for 3 months after completion of the treatment protocol.
Measure Participants	10	15
Count of Participants [Participants]	3 21.4%	3 20%

9. Secondary Outcome

Title	Time to First Anti-MRSA Antibiotics (After Treatment Period)
Description	Time between completion of Study Drug and need for anti-MRSA antibiotics to control or treat symptoms
Time Frame	Completion of Study Drug to Day 118

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics	Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	In the experimental arm CF participants were 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 were followed for 3 months after completion of the treatment protocol.	In the active comparator arm CF participants were randomized to 28 days of inhaled sterile placebo (saline) and 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 were followed for 3 months after completion of the treatment protocol.
Measure Participants	10	15
Mean (Standard Deviation) [days]	NA (NA)	58 (15)

Adverse Events

Time Frame	Adverse events were collected from the time of enrollment until 3 months after completion of treatment.
Adverse Event Reporting Description	Adverse events were collected at each study visit as per protocol
Arm/Group Title	Inhaled Vancomycin and Oral Antibiotics		Inhaled Placebo (Sterile Water) and Oral Antibiotics
Arm/Group Description	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.		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.
All Cause Mortality
	Inhaled Vancomycin and Oral Antibiotics		Inhaled Placebo (Sterile Water) and Oral Antibiotics
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/15 (0%)
Serious Adverse Events
	Inhaled Vancomycin and Oral Antibiotics		Inhaled Placebo (Sterile Water) and Oral Antibiotics
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		3/15 (20%)
Gastrointestinal disorders
Bowel Obstruction	1/14 (7.1%)		0/15 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Exacerbation	0/14 (0%)		3/15 (20%)
Other (Not Including Serious) Adverse Events
	Inhaled Vancomycin and Oral Antibiotics		Inhaled Placebo (Sterile Water) and Oral Antibiotics
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100%)		14/15 (93.3%)
Gastrointestinal disorders
Diarrhea	7/14 (50%)		2/15 (13.3%)
Nausea	4/14 (28.6%)		2/15 (13.3%)
Heartburn	2/14 (14.3%)		4/15 (26.7%)
General disorders
Chest Pain	3/14 (21.4%)		2/15 (13.3%)
Nervous system disorders
Headache	3/14 (21.4%)		5/15 (33.3%)
Respiratory, thoracic and mediastinal disorders
Cough	8/14 (57.1%)		3/15 (20%)
Nasal Congestion	4/14 (28.6%)		6/15 (40%)
Throat Symptoms	5/14 (35.7%)		3/15 (20%)
Chest Tightness	4/14 (28.6%)		4/15 (26.7%)
Shortness of Breath	3/14 (21.4%)		1/15 (6.7%)
Drop in FEV1	3/14 (21.4%)		1/15 (6.7%)
Increase in Sputum Production	1/14 (7.1%)		3/15 (20%)
Chest Congestion	1/14 (7.1%)		3/15 (20%)
Pulmonary Exacerbation	0/14 (0%)		3/15 (20%)

Limitations/Caveats

Easy termination leading to smaller number of subjects analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.