To evaluate the micro-biologic efficacy and safety of a streamlined treatment for early onset methicillin-resistant staphylococcus aureus (MRSA) in patients with cystic fibrosis.
This is an open-label, multi-center interventional trial in Cystic Fibrosis (CF) patients with new MRSA isolated from the respiratory tract (oropharyngeal (OP) = 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. A subsequent visit will be 3 months later with their routine clinic appointment. 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. Due to COVID 19 restrictions, a study amendment was filed in March 2020 for subjects currently active subjects that allowed remote study visit for V3 and V4. Cultures were collected at home and mailed to the Core Study lab, clinical case forms and surveys were completed via video visits. These changes were approved by each study site that this was relevant to i.e. 4 study sites had subjects active at that time.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Dosing if \< 40 kg: 8 mg/kg trimethoprim/40 mg/kg trimethoprim sulfamethoxazole given twice daily for 14 days during Days 1-14 and Days 29-42. Dosing is ≥ 40 kg: 320 mg/1600 mg twice daily for 14 days during Days 1-14 and Days 29-42.
If a subject has an allergy to or intolerance to TMP/SMX, they may be treated with minocycline provided they are 8 years of age or older. Dosing if \< 50 kg: 2 mg/kg orally twice daily for 14 days during Days 1-14 and Days 29-42. Dosing if ≥ 50 kg: 100 mg twice daily for 14 days during Days 1-14 and Days 29-42.
1 gram 2% nasal ointment generously applied to each nostril using a cotton swab twice daily for 5 days during Days 1-5 and Days 29-33.
National Jewish Health
Denver, Colorado, United States
Indiana University
Indianapolis, Indiana, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
Proportion of STAR-TER subjects with a negative MRSA culture at Day 28 vs. observational arm of historic STAR-Too trial
Descriptive summary with corresponding 95% confidence interval.
Time frame: Day 28
Proportion of subjects with a protocol-defined pulmonary exacerbation between Baseline and Day 28 treated with antibiotics active against MRSA
Pulmonary exacerbation is defined as having 1 of the major criteria or 2 minor signs/symptoms and fulfillment of symptom duration. Major criteria: 1. Absolute decrease in FEV1 of ≥ 10% from Visit 1 (Baseline), unresponsive to albuterol (in participants able to reproducibly perform spirometry) 2. Oxygen saturation \<90% on room air or absolute decrease of ≥ 5% from Visit 1 3. New lobar infiltrate(s) or atelectasis on chest radiograph 4. Hemoptysis (more than streaks on more than one occasion in past week) Minor signs/symptoms: 1. Increased work of breathing or respiratory rate 2. New or increased adventitial sounds on lung exam 3. Weight loss ≥5% of body weight or decrease across 1 major percentile in weight percentile for age in past 6 months 4. Increased cough 5. Decreased exercise tolerance or level of activity 6. Increased chest congestion or change in sputum Signs/symptoms duration: initial symptom must have occurred for at least 5 days.
Time frame: Period ranging from start of Baseline and continuing through Day 28
Proportion of subjects with a protocol-defined pulmonary exacerbation between Baseline and Day 28 treated with any oral, inhaled, or IV antibiotics regardless of potential activity against MRSA
Pulmonary exacerbation is defined as having 1 of the major criteria or 2 of the minor signs/symptoms and fulfillment of symptom duration. Major criteria: 1. Absolute decrease in FEV1 of ≥ 10% from Visit 1 (Baseline), unresponsive to albuterol (in participants able to reproducibly perform spirometry) 2. Oxygen saturation \<90% on room air or absolute decrease of ≥ 5% from Visit 1 3. New lobar infiltrate(s) or atelectasis on chest radiograph 4. Hemoptysis (more than streaks on more than one occasion in past week) Minor signs/symptoms: 1. Increased work of breathing or respiratory rate 2. New or increased adventitial sounds on lung exam 3. Weight loss ≥5% of body weight or decrease across 1 major percentile in weight percentile for age in past 6 months 4. Increased cough 5. Decreased exercise tolerance or level of activity 6. Increased chest congestion or change in sputum Signs/symptoms duration: initial symptom must have occurred for at least 5 days.
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For subjects able to swish without swallowing, 0.12% chlorhexidine gluconate oral rinse will be used twice daily for 14 days during Days 1-14 and Days 29-42.
Subjects will be instructed to wipe down all high touch surfaces and medical equipment with surface disinfection wipes daily during Days 1-21 and Days 29-49. Subjects will also be instructed to wash all linens and towels in hot water once weekly during weeks 1-3 and weeks 5-7.
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
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Texas Children's Hospital, Baylor College of Medicine
Houston, Texas, United States
University of Washington Medical Center and Seattle Children's
Seattle, Washington, United States
Time frame: Period ranging from start of Baseline and continuing through Day 28
Proportion of subjects treated with oral, inhaled, and IV antibiotics over the six-month study
Time frame: Period ranging from start of Baseline and continuing through Month 6
Time to protocol-defined pulmonary exacerbation over the six-month study
Pulmonary exacerbation is defined as having 1 of the major criteria or 2 of the minor signs/symptoms and fulfillment of symptom duration. Major criteria: 1. Absolute decrease in FEV1 of ≥ 10% from Visit 1 (Baseline), unresponsive to albuterol (in participants able to reproducibly perform spirometry) 2. Oxygen saturation \<90% on room air or absolute decrease of ≥ 5% from Visit 1 3. New lobar infiltrate(s) or atelectasis on chest radiograph 4. Hemoptysis (more than streaks on more than one occasion in past week) Minor signs/symptoms: 1. Increased work of breathing or respiratory rate 2. New or increased adventitial sounds on lung exam 3. Weight loss ≥5% of body weight or decrease across 1 major percentile in weight percentile for age in past 6 months 4. Increased cough 5. Decreased exercise tolerance or level of activity 6. Increased chest congestion or change in sputum Signs/symptoms duration: initial symptom must have occurred for at least 5 days.
Time frame: Period ranging from start of Baseline and continuing through Month 6
Number of protocol-defined pulmonary exacerbations over the six-month study
Pulmonary exacerbation is defined as having 1 of the major criteria or 2 of the minor signs/symptoms and fulfillment of symptom duration. Major criteria: 1. Absolute decrease in FEV1 of ≥ 10% from Visit 1 (Baseline), unresponsive to albuterol (in participants able to reproducibly perform spirometry) 2. Oxygen saturation \<90% on room air or absolute decrease of ≥ 5% from Visit 1 3. New lobar infiltrate(s) or atelectasis on chest radiograph 4. Hemoptysis (more than streaks on more than one occasion in past week) Minor signs/symptoms: 1. Increased work of breathing or respiratory rate 2. New or increased adventitial sounds on lung exam 3. Weight loss ≥5% of body weight or decrease across 1 major percentile in weight percentile for age in past 6 months 4. Increased cough 5. Decreased exercise tolerance or level of activity 6. Increased chest congestion or change in sputum Signs/symptoms duration: initial symptom must have occurred for at least 5 days.
Time frame: Period ranging from start of Baseline and continuing through Month 6
MRSA Culture Status
Proportion of subjects with a negative culture for MRSA at Day 56
Time frame: Day 56
Proportion of subjects with >80% compliance for study drug during the first 28 days
Compliance refers to the amount of prescribed medication consumed.
Time frame: Day 28