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Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis

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: NCT02547116
Recruitment Status : Suspended (Administrative delay)
First Posted : September 11, 2015
Last Update Posted : January 14, 2020
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE September 9, 2015
First Posted Date  ICMJE September 11, 2015
Last Update Posted Date January 14, 2020
Estimated Study Start Date  ICMJE December 2020
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2015)
change in small colony variant Staph. aureus colony forming units on induced sputum respiratory culture [ Time Frame: Culture specimens obtained at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2015)
  • change in lung function, as measured by forced expiratory volume in one second (FEV1) [ Time Frame: FEV1 measured at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention ]
  • patient reported symptoms/quality of life, as captured in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) [ Time Frame: CFQ-R administered at: Baseline, within 2 weeks of end of standard antibiotic course (control), 1 week prior to intervention, and within 2 weeks of end of intervention ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis
Official Title  ICMJE Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis
Brief Summary

Methicillin-susceptible (MSSA) and Methicillin-resistant (MRSA) Staphylococcus aureus (SA) are two of the most important infectious pathogens in CF, with 69% of CF patients having lung infection with MSSA or MRSA in the last year. Wolter and co-workers recently demonstrated that a specific morphologic subtype of MSSA and MRSA, small-colony variant Staph aureus (SCV-SA), is associated with greater decline in lung function and worse clinical outcomes. SCV-SA is already recognized for its ability to contribute to persistent infection, likely due to SCV-SA's ability for intracellular growth, as well as its increased antibiotic resistance compared to normal-colony SA. To investigate the epidemiology and clinical significance of SCV-SA in CF, and explore the hypothesis that SCV-SA may require unique antibiotic treatment strategies to optimize clinical response, the investigators will perform the following:

  1. Characterize the epidemiology of SCV-SA infection in both an adult and pediatric CF population and investigate the clinical significance of SCV-SA infection in CF by comparing clinical characteristics and outcomes of CF patients with SCV-SA compared to those with to normal-colony MSSA/MRSA.
  2. Characterize the unique microbiologic characteristics of SCV-SA infection in CF by evaluating antibiotic susceptibility profiles and molecular characteristics of SCV-SA in a two large CF patient populations.
  3. Perform a 16-patient pilot study of a novel treatment for SCV-SA infection in CF, utilizing low dose rifampin in combination with standard anti-SA antibiotics.

These investigations will delineate the role of SCV-SA as a pathogen in CF and provide guidance to optimize treatment strategies of MSSA/MRSA CF lung infection.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cystic Fibrosis
  • MRSA
Intervention  ICMJE Drug: Rifampin
Addition of Rifampin to standard anti-Staphylococcal treatment regimen
Study Arms  ICMJE
  • No Intervention: Standard anti-staphylococcal antibiotic
  • Experimental: Standard anti-staphylococcal antibiotic + Rifampin
    Individuals with known, persistent small-colony variant MRSA, who are treated with standard anti-staphylococcal antibiotics, will be treated with their standard therapy in addition to Rifampin.
    Intervention: Drug: Rifampin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: September 10, 2015)
16
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 SCV-SA respiratory cultures in the last two years at least six months apart, plus a positive SCV-SA respiratory culture at Screening Visit and Run-in (Day -14) Visit.
  5. FEV1 >30% of predicted normal for age, gender, and height at Screening.
  6. Weight > 35 kg
  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 14 days of the screening visit.
  2. Use of oral or inhaled anti-MRSA drugs within two weeks of the Screening Visit.
  3. History of intolerance to rifampin or TMP/SMX, minocycline, and doxycycline.
  4. Resistance to rifampin or TMP/SMX, minocycline and doxycycline at screening.
  5. Abnormal renal function, defined as creatinine clearance <50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening.
  6. 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.
  7. Serum hematology or chemistry results which in the judgment of the investigator would interfere with completion of the study.
  8. History of or listed for solid organ or hematological transplantation
  9. History of sputum culture with non-tuberculous Mycobacteria in the last 6 months.
  10. History of sputum culture with Burkholderia Cepacia in the last year.
  11. Planned continuous use of soft contact lenses while taking rifampin and no access to glasses.
  12. Taking voriconazole and unable to discontinue its use while enrolled in the study.
  13. Administration of any investigational drug or device within 28 days of screening or within 6 half-lives of the investigational drug (whichever is longer)
  14. Female patients of childbearing potential who are pregnant or lactating, or plan on becoming pregnant
  15. 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.
  16. Patients taking certain drugs will be excluded from the study:

    a. Drugs, which are contraindicated when rifampin is used (in addition to voriconazole): i. Antiretrovirals: fosamprenavir, atazanavir, lopinavir, saquinavir, nelfinavir, tipranavir, darunavir, rilpivirine,telaprevir, boceprevir, elvitegravir, maraviroc ii. Drugs used to increase systemic exposure of antiretrovirals: Cobicistat iii. Anthelmintic/Antimalarial agents: praziquantel, artemether iv. Antianginal agent: ranolazine v. Psychiatric medications: lurasidone b. Other drugs, not contraindicated, but listed as having major drug to drug interactions i. Antiretrovirals: ritonavir, indinavir, efavirenz, nevirapine, etavirine

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02547116
Other Study ID Numbers  ICMJE IRB00047491
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark T Jennings, MD, MHS Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP