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

NCT01349192 | Terminated Phase 2 Results DMC

• 1 other identifier: STAR-too-10K0
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 13

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.

Conditions

Cystic Fibrosis; Methicillin-resistant Staphylococcus Aureus

Keywords

MRSA; Cystic Fibrosis; Early Infection; Treatment

Outcome Measures

Primary Outcomes (1)

• MRSA Culture Status

  Proportion of subjects with a negative culture for MRSA at Day 28.

  Day 28

Secondary Outcomes (3)

• Antibiotic Use (Proportion of Subjects)

  6 months

• Antibiotic Use (Days of Use Per Subject)

  6 months

• Pulmonary Exacerbations

  28 days

Study Arms (2)

Treatment

EXPERIMENTAL

Subjects are treated with two oral antibiotics, topical antibiotics, and are instructed to use environmental decontamination techniques.

Drug: Rifampin; Drug: Trimethoprim/Sulfamethoxazole; Drug: Minocycline; Drug: Mupirocin; Drug: chlorhexidine gluconate oral rinse; Drug: 2% Chlorhexidine solution wipes; Behavioral: Environmental Decontamination

Observational

NO INTERVENTION

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.

Interventions

Rifampin DRUG

Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: \<40kg : 15mg/kg daily for 14 days divided every 12 hours.

Also known as: Rifadin, Rimactane

Treatment

Trimethoprim/Sulfamethoxazole DRUG

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.

Also known as: Bactrim, Septra

Treatment

Minocycline DRUG

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.

Also known as: Cleeravue-M, Dynacin, Minocin, Myrac, Solodyn, Vectrin

Treatment

Mupirocin DRUG

1 gram 2% nasal ointment generously applied to each nostril using a cotton swab twice daily for 14 days.

Also known as: Bactroban, Centany

Treatment

chlorhexidine gluconate oral rinse DRUG

for subjects able to swish without swallowing. 0.12% chlorhexidine gluconate oral rinse twice daily for 14 days.

Treatment

2% Chlorhexidine solution wipes DRUG

whole body wash solution wipes once daily for first 5 days.

Treatment

Environmental Decontamination BEHAVIORAL

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.

Also known as: Sani-Cloth Plus

Treatment

Eligibility Criteria

• Age: 4 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female ≥ 4 and ≤ 45 years of age at the Screening Visit.
• 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)
• 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)
• Clinically stable with no significant changes in health status within the 14 days prior to screening
• 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.

You may not qualify if:

• Received antibiotics with activity against MRSA within 28 days prior to screening (see study manual for list of antibiotics)
• Use of an investigational agent within 28 days prior to screening
• 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
• MRSA from the screening culture resistant to rifampin OR resistant to both TMP/SMX and minocycline
• History of intolerance to oral rifampin, or topical chlorhexidine or mupirocin
• History of intolerance to both TMP/SMX and minocycline
• \< 8 years of age and either allergic or intolerant to TMP/SMX or screening MRSA resistant to TMP/SMX
• ≥ 8 years of age and allergic or intolerant to TMP/SMX and screening MRSA resistant to minocycline
• ≥ 8 years of age and allergic or intolerant to minocycline and screening MRSA resistant to TMP/SMX
• For females of child bearing potential: pregnant, breastfeeding, or unwilling to use barrier contraception through Day 15 of the study
• Abnormal renal function at Screening, defined as estimated creatinine clearance \<50 mL/min using the Cockcroft-Gault equation
• 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)
• History of solid organ or hematological transplantation
• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• CF Therapeutics Development Network Coordinating Center: collaborator
• Seattle Children's Hospital: collaborator
• Washington University School of Medicine: collaborator
• University of Washington: collaborator
• University of Colorado, Denver: collaborator
• Baylor College of Medicine: collaborator
• University of Alabama at Birmingham: collaborator
• Cook Children's Medical Center: collaborator
• University of Michigan: collaborator
• University of Florida: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• St. Louis Children's Hospital: collaborator

Study Sites (13)

The Children's Hospital-University of Birmingham

Birmingham, Alabama, 35233, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109-5212, United States

Location

Children's Hospitals and Clinics of Minnesota Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

N.C Memorial Hospital and N.C Children's Hospital

Chapel Hill, North Carolina, 27599, United States

Location

CFF Care Center & Pediatric Program Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3026, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's

Seattle, Washington, 98145-9807, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (2)

• Lo DK, Muhlebach MS, Smyth AR. Interventions for the eradication of meticillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis. Cochrane Database Syst Rev. 2022 Dec 13;12(12):CD009650. doi: 10.1002/14651858.CD009650.pub5.

  PMID: 36511181 DERIVED

• Muhlebach MS, Beckett V, Popowitch E, Miller MB, Baines A, Mayer-Hamblett N, Zemanick ET, Hoover WC, VanDalfsen JM, Campbell P, Goss CH; STAR-too study team. Microbiological efficacy of early MRSA treatment in cystic fibrosis in a randomised controlled trial. Thorax. 2017 Apr;72(4):318-326. doi: 10.1136/thoraxjnl-2016-208949. Epub 2016 Nov 15.

  PMID: 27852955 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Infections

Interventions

Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination; Minocycline; Mupirocin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Drug Combinations; Pharmaceutical Preparations; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Epoxy Compounds; Ethers, Cyclic; Ethers; Pyrans; Fatty Acids; Lipids

Limitations and Caveats

The study was completed prior to reaching the pre-specified number of participants as the Data Safety Monitoring committee observed that efficacy had been reached.

Results Point of Contact

• Title: Marianne S. Muhlebach, PI
• Organization: University of North Carolina, Chapel Hill

Marianne_Muhlebach@med.unc.edu

(1) 919 966 1055

Study Officials

• Marianne S Muhlebach, MD

  UNC Children's Hospital

  PRINCIPAL INVESTIGATOR

• Chris Goss, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Pediatric Pulmonolgy

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 6, 2011
• Study Start: April 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 15, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)