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

NCT ID: NCT01349192

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2015-05-31

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.

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.

Conditions

Cystic Fibrosis; Methicillin-resistant Staphylococcus Aureus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Treatment

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

Group Type: EXPERIMENTAL

Rifampin

Intervention Type: DRUG

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

Trimethoprim/Sulfamethoxazole

Intervention Type: 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.

Minocycline

Intervention Type: 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.

Mupirocin

Intervention Type: DRUG

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

chlorhexidine gluconate oral rinse

Intervention Type: DRUG

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

2% Chlorhexidine solution wipes

Intervention Type: DRUG

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

Environmental Decontamination

Intervention Type: 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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Rifampin

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Mupirocin

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

Intervention Type: DRUG

chlorhexidine gluconate oral rinse

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

Intervention Type: DRUG

2% Chlorhexidine solution wipes

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

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

Other Intervention Names

Rifadin, Rimactane; Bactrim, Septra; Cleeravue-M, Dynacin, Minocin, Myrac, Solodyn, Vectrin; Bactroban, Centany; Sani-Cloth Plus

Eligibility Criteria

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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CF Therapeutics Development Network Coordinating Center

NETWORK

Sponsor Role: collaborator

Seattle Children's Hospital

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Cook Children's Medical Center

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: collaborator

St. Louis Children's Hospital

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Marianne Muhlebach, MD

Professor, Pediatric Pulmonolgy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marianne S Muhlebach, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Children's Hospital

Chris Goss, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

The Children's Hospital-University of Birmingham

Birmingham, Alabama, United States

The Children's Hospital

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Children's Hospitals and Clinics of Minnesota Minneapolis

Minneapolis, Minnesota, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

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

Chapel Hill, North Carolina, United States

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

Cincinnati, Ohio, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Seattle Children's

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36511181 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27852955 (View on PubMed)

Other Identifiers

STAR-too-10K0

Identifier Type: -

Identifier Source: org_study_id