Early MRSA therapy in CF (streamlined eradication with repeat cycle)(STaph Aureus Resistance-Treat Early and Repeat (STAR-TER)
Study ID: STU 022018-089
This is an open-label, multi-center interventional trial in CF patients with new MRSa isolated from the respiratory tract (oropharyngeal [?] oP swab, sputum, or bronchoscopy) at a clinical encounter. Forty-two subjects with new MRSa infection will be enrolled and will receive two weeks of oral trimethoprim-sulfamethoxazole (TMP-SMX) or minocycline depending on age, allergies and antibiotic resistance of prior isolate for 14 days, and nasal mupirocin for 5 days. Subjects old enough to do so will use oral disinfectant gurgle (0.12% chlorhexidine gluconate oral rinse) for 14 days. The primary endpoint will be the proportion of positive MRSa respiratory cultures at Day 28 and this will be compared to our prior STaR-Too results. Subjects will then have a 14 day wash-out period (i.e. no TMP-SMX or minocycline from Day 14 to Day 28) and all participants will repeat the treatment protocol from Day 29 to Day 42. Repeat cultures will be done at day 56 (+-) 7 days, most likely combined with their next clinic visit. Results of Day 56 cultures will be an exploratory, secondary outcome. Subsequent visits will be 3 and 6 months later with their routine clinic appointments. any interim clinic visits will be used to obtain repeat cultures and clinical data. assessment of MRSa culture status will be by oP swab for all subjects, with additional sputum in those who expectorate. Total duration of an individual subject's participation will be six months. Total duration of the study is expected to be 42 months, which includes data analyses and publication. Contemporaneous Clinical Care Comparison arm: Subjects with incident MRSa who are not interested in a protocolized study but otherwise eligible will be offered an opportunity to be part of the clinical care arm. if consenting, clinical data (MRSa culture status, antibiotic treatments, lung function etc.) will be collected for exploratory analyses comparing clinical outcomes of MRSa management outside the confines of a protocolized trial.
Inclusion Criteria: 1. Male or female >= 2 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: a. sweat chloride >= 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT) b. two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene c. 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 MRSA colonization defined as: a. First MRSA colonization: first life-time documented isolation of MRSA from respiratory tract. Occurrence no longer than 6 months prior to screening OR b. Early MRSA colonization: * MRSA was previously isolated from the respiratory tract <= 2 times over the past 3.5 years, but this was followed by at least 1 year of documented negative cultures for MRSA as noted below: * At least 2 cultures performed a minimum of 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. MRSA isolate is available for testing in central lab x either isolated at the screening visit or available from the most recent clinic visit that qualified the subject as eligible 5. Written informed consent (and assent when applicable) obtained from subject[Single Quote]s legal representative and ability for subject/family to comply with the requirements of the study Inclusion Criteria for Parents: 1. Parent contacts for CF patient eligible for the study Inclusion Criteria for Household Members: 1. Household contacts for CF patient eligible for the study
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- PREETI BHATIA SHARMA
UNIVERSITY OF NC AT CHAPEL HILL
To evaluate the microbiologic efficacy and safety of a streamlined two week MRSa eradication treatment protocol. 1.evaluate adherence to the MRSa eradication treatment protocol 2.Preliminary data on clinical outcomes (FeV1 and Weight) 3.assess the microbiologic efficacy and safety of repeated treatment, in regards to achieving culture negative status in those failing the first cycle or reduction of recurrence in those subjects who are MRSa negative after the first treatment course. although there will be few subjects this can be compared to the initial trial where many subjects received antibiotics after Day 28. 4.assess treatment burden and side effects of this streamlined protocol compared to the prior dual-antibiotic treatment. 5.Compare those participating in the study to those non-participants willing to consent to having their clinical data collected during routine clinic encounters. 6.Monitor for emergence of drug resistances or small colony variants after the first or second treatment cycle. Mechanistic endpoint: Frequency of MRSa nasal colonization in any household member of the study subject. Please refer to Section 2 of the protocol for the study rationale.