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Early Methicillin-resistant Staphylococcus Aureus (MRSA) Therapy in Cystic Fibrosis (CF) (STAR-Too)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01349192
Recruitment Status : Terminated (Interim review showed a statistically significant treatment effect and the DMC recommended that the study be stopped with ongoing follow-up of enrolled subjects)
First Posted : May 6, 2011
Results First Posted : May 15, 2017
Last Update Posted : May 15, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

Purpose: There has been a recent, rapid increase in prevalence of Methicillin-resistant Staphylococcus aureus (MRSA) among patients with Cystic Fibrosis (22% across US CF centers in 2009). Some epidemiologic studies suggest possible worse outcomes, a recent analyses showing this with chronic but not intermittent MRSA. Given the chronic difficult to treat lung infections in CF it is unclear how the onset of MRSA should be approached. This randomized, controlled, interventional study seeks to determine if an early eradication protocol is effective for eradication of MRSA and will provide an opportunity to obtain data regarding early clinical impact of new isolation of MRSA.

Participants: Cystic fibrosis patients with new isolation of MRSA from their respiratory culture on a routine clinic visit.

Procedures (methods): Randomized, open-label, multi-center study comparing use of an eradication protocol to an observational group who receives the current standard of care i.e. treatment for MRSA only with pulmonary exacerbations.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Methicillin-resistant Staphylococcus Aureus Drug: Rifampin Drug: Trimethoprim/Sulfamethoxazole Drug: Minocycline Drug: Mupirocin Drug: chlorhexidine gluconate oral rinse Drug: 2% Chlorhexidine solution wipes Behavioral: Environmental Decontamination Phase 2

Detailed Description:
The STAR-too study is a randomized, open label, multi-center study in CF patients with new MRSA isolated from the respiratory tract (sputum or oropharyngeal (OP) swab). The purpose of the study is to compare use of a two week eradication treatment protocol to an observational group treated for MRSA only when respiratory symptoms meet the criteria for a protocol defined pulmonary exacerbation during the first 28 days of the study. A total of 90 participants, four years of age or older, with new MRSA infection are planned to be randomized in a 1:1 fashion to either the treatment arm or to the observational control arm. Randomization is stratified by age, P. aeruginosa status at screening and site. Each participant randomized to the treatment arm receives two oral antibiotics for 14 days, topical antibacterial treatment of skin and nares, and a three week environmental decontamination for high risk areas and equipment. Each participant randomized to the observational control arm is followed clinically with usual care except to treat new or worsening pulmonary symptoms with antibiotics between screening and Day 28 only when participant meets criteria for a protocol defined exacerbation. Participants continue in the study for 6 months with study visits at Day 84 and Day 168 corresponding with their normal quarterly visits, this extension of observation provides additional data regarding natural history of MRSA infection and durability of the eradication protocol. The primary outcome is the proportion of participants with MRSA eradicated from respiratory tract cultures at Day 28. The secondary outcomes number of, and time to, pulmonary exacerbations, and use of antibiotics.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Masking Description: Although this is an open-label study, the PIs and operational study team will remain blinded to the study arm assignments of the aggregate study population and will not view aggregate study results by study arm until after database lock.
Primary Purpose: Treatment
Official Title: Early MRSA Therapy in CF - Culture Based vs. Observant Therapy (Treat or Observe) (Star-TOO - STaph Aureus Resistance - Treat or Observe)
Actual Study Start Date : April 2011
Primary Completion Date : January 2015
Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Treatment
Subjects are treated with two oral antibiotics, topical antibiotics, and are instructed to use environmental decontamination techniques.
Drug: Rifampin
Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: <40kg : 15mg/kg daily for 14 days divided every 12 hours.
Other Name: Rifadin, Rimactane
Drug: Trimethoprim/Sulfamethoxazole
Adult Dose: 320/1600 orally twice daily for 14 days. Pediatric Dose: <40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.
Other Name: Bactrim, Septra
Drug: Minocycline

only subjects greater or equal to 8 years of age, who are not able to tolerate TMP/SMX or whose screening MRSA is resistant to TMP/SMX should be prescribed minocycline.

Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: < 50 kg : 2mg/kg orally twice daily for 14 days not to exceed 200mg per day.

Other Name: Cleeravue-M, Dynacin, Minocin, Myrac, Solodyn, Vectrin
Drug: Mupirocin
1 gram 2% nasal ointment generously applied to each nostril using a cotton swab twice daily for 14 days.
Other Name: Bactroban, Centany
Drug: chlorhexidine gluconate oral rinse
for subjects able to swish without swallowing. 0.12% chlorhexidine gluconate oral rinse twice daily for 14 days.
Drug: 2% Chlorhexidine solution wipes
whole body wash solution wipes once daily for first 5 days.
Behavioral: Environmental Decontamination

wipe down high touch surfaces and medical equipment with surface disinfecting wipes daily for the first 21 days.

wash all linens and towels in hot water once weekly for three weeks.

Other Name: Sani-Cloth Plus
No Intervention: Observational
Subjects are tracked and not treated for their MRSA. If the subject reaches a protocol defined exacerbation within the first 28 days then they will be treated per choice of their primary Pulmonologist.

Outcome Measures

Primary Outcome Measures :
  1. MRSA Culture Status [ Time Frame: Day 28 ]
    Proportion of subjects with a negative culture for MRSA at Day 28.

Secondary Outcome Measures :
  1. Antibiotic Use (Proportion of Subjects) [ Time Frame: 6 months ]
    Proportion of subjects treated with oral, inhaled, and IV antibiotics over the 6 month study.

  2. Antibiotic Use (Days of Use Per Subject) [ Time Frame: 6 months ]
    Days of use of oral, inhaled, and IV antibiotics over the 6 month study.

  3. Pulmonary Exacerbations [ Time Frame: 28 days ]
    Proportion of subjects with a protocol-defined pulmonary exacerbation (PE) between baseline and day 28 who are treated with antibiotics active against MRSA.

Eligibility Criteria

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Ages Eligible for Study:   4 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female ≥ 4 and ≤ 45 years of age at the Screening Visit.
  2. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

    • sweat chloride ≥ 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)
    • two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene
    • Abnormal nasal potential difference (change in NPD in response to a low chloride solution and isoproteronol of less than -5 mV)
  3. First OR early repeat MRSA colonization defined as:

    • First MRSA colonization: first documented isolation of MRSA from respiratory tract occurred ≤ 6 months prior to screening
    • OR Early repeat MRSA colonization:

    MRSA was previously isolated from the respiratory tract (≤ 2 times), but this was followed by at least 1 year of documented negative cultures for MRSA as noted below:

    -- At least 2 cultures performed at least 3 months apart to document 1 year of culture negativity. Each of these cultures should be documented to have been collected at least 1 week after end of any antibiotic prescription with MRSA activity.

    Patient again recently positive for MRSA from the respiratory tract (within 6 months prior to screening)

  4. Clinically stable with no significant changes in health status within the 14 days prior to screening
  5. 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

A repeat culture from the respiratory tract is obtained at screening but does not have to be positive to be able to enter the study.

Exclusion Criteria:

  1. Received antibiotics with activity against MRSA within 28 days prior to screening (see study manual for list of antibiotics)
  2. Use of an investigational agent within 28 days prior to screening
  3. For subjects ≥ 6 years of age: FEV1 at screening < 30% of predicted for age based on the Wang (males < 18 years, females < 16 years) or Hankinson (males ≥ 18 years, females ≥ 16 years) standardized equations
  4. MRSA from the screening culture resistant to rifampin OR resistant to both TMP/SMX and minocycline
  5. History of intolerance to oral rifampin, or topical chlorhexidine or mupirocin
  6. History of intolerance to both TMP/SMX and minocycline
  7. < 8 years of age and either allergic or intolerant to TMP/SMX or screening MRSA resistant to TMP/SMX
  8. ≥ 8 years of age and allergic or intolerant to TMP/SMX and screening MRSA resistant to minocycline
  9. ≥ 8 years of age and allergic or intolerant to minocycline and screening MRSA resistant to TMP/SMX
  10. For females of child bearing potential: pregnant, breastfeeding, or unwilling to use barrier contraception through Day 15 of the study
  11. Abnormal renal function at Screening, defined as estimated creatinine clearance <50 mL/min using the Cockcroft-Gault equation
  12. Abnormal liver function at the time of screening, defined as ≥2x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT)
  13. History of solid organ or hematological transplantation
  14. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01349192

United States, Alabama
The Children's Hospital-University of Birmingham
Birmingham, Alabama, United States, 35233
United States, Colorado
The Children's Hospital
Aurora, Colorado, United States, 80045
United States, Florida
University of Florida
Gainesville, Florida, United States, 32611
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109-5212
United States, Minnesota
Children's Hospitals and Clinics of Minnesota Minneapolis
Minneapolis, Minnesota, United States, 55404
United States, Missouri
St. Louis Children's Hospital
St. Louis, Missouri, United States, 63110
United States, North Carolina
N.C Memorial Hospital and N.C Children's Hospital
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
CFF Care Center & Pediatric Program Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3026
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's
Seattle, Washington, United States, 98145-9807
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of North Carolina, Chapel Hill
CF Therapeutics Development Network Coordinating Center
Seattle Children's Hospital
Washington University School of Medicine
University of Washington
University of Colorado, Denver
Baylor College of Medicine
University of Alabama at Birmingham
Cook Children's Medical Center
University of Michigan
University of Florida
University of Texas Southwestern Medical Center
Children's Hospital Medical Center, Cincinnati
St. Louis Children's Hospital
Principal Investigator: Marianne S Muhlebach, MD UNC Children's Hospital
Principal Investigator: Chris Goss, MD University of Washington
More Information

Responsible Party: Marianne Muhlebach, MD, Professor, Pediatric Pulmonolgy, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01349192     History of Changes
Other Study ID Numbers: STAR-too-10K0
First Posted: May 6, 2011    Key Record Dates
Results First Posted: May 15, 2017
Last Update Posted: May 15, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Marianne Muhlebach, MD, University of North Carolina, Chapel Hill:
Cystic Fibrosis
Early Infection

Additional relevant MeSH terms:
Cystic Fibrosis
Staphylococcal Infections
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Gram-Positive Bacterial Infections
Bacterial Infections
Chlorhexidine gluconate
Anti-Infective Agents, Local
Anti-Infective Agents
Dermatologic Agents
Anti-Bacterial Agents
Antibiotics, Antitubercular
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action