STaph Aureus Resistance-Treat Early and Repeat (STAR-TER)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 9
- 主要终点
- Proportion of STAR-TER subjects with a negative MRSA culture at Day 28 vs. observational arm of historic STAR-Too trial
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 2 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 milliequivalents/liter by quantitative pilocarpine iontophoresis test (QPIT)
- •two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene
- •abnormal nasal potential difference(NPD) (change in NPD in response to a low chloride solution and isoproteronol of less than -5 mV)
- •First OR early MRSA colonization defined as:
- •First MRSA colonization: first documented isolation of MRSA from respiratory tract occurred ≤ 6 months prior to screening
- •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
- •MRSA is available to the central laboratory - either the incident MRSA isolate from the clinic visit or the subject is MRSA positive at the screening visit
- •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
排除标准
- •Received antibiotics with activity against MRSA within 28 days prior to screening
- •Use of an investigational agent within 28 days prior to screening
- •For subjects ≥ 6 years of age: FEV1 at screening < 25% 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 or the most recent clinical care visit within 6 months prior to screening resistant to TMP/SMX
- •History of intolerance to topical chlorhexidine or mupirocin
- •History of intolerance to both TMP/SMX and minocycline
- •< 8 years of age and allergic or intolerant to TMP/SMX
- •≥ 8 years of age and allergic or intolerant to TMP/SMX and MRSA isolate (from screening or clinical care visit)is resistant to minocycline
- •For females of child bearing potential: pregnant, breastfeeding, or unwilling to use barrier contraception through Day 42 of the study
- •Subjects with history of abnormal renal function will need screening labs showing normal function Abnormal renal function is defined as estimated creatinine clearance <50 mL/min using the:
- •Bedside Schwartz Equation for subjects <18 years of age, and
- •Levey Glomerular filtration rate (GFR) Equation for subjects ≥ 18 years of age.
- •Subjects with a history of abnormal liver function will need to have screening labs showing normal transaminases. Liver dysfunction is defined as ≥3x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT) or abnormal synthetic function
- •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.
研究组 & 干预措施
Treatment
Subjects are treated with one oral antibiotic, one topical antibiotic, an oral rinse, and instructed to use environmental decontamination techniques.
Trimethoprim Sulfamethoxazole (TMP/SMX) is the primary oral antibiotic to be used. Subjects with allergy or intolerance to TMP_SMX will use minocycline as an alternative antibiotic. Topical antibiotics are nasal Mupirocin, and the oral rinse/gurgle with 0.12% chlorhexidine gluconate.
干预措施: Trimethoprim Sulfamethoxazole (TMP/SMX) (Drug)
Treatment
Subjects are treated with one oral antibiotic, one topical antibiotic, an oral rinse, and instructed to use environmental decontamination techniques.
Trimethoprim Sulfamethoxazole (TMP/SMX) is the primary oral antibiotic to be used. Subjects with allergy or intolerance to TMP_SMX will use minocycline as an alternative antibiotic. Topical antibiotics are nasal Mupirocin, and the oral rinse/gurgle with 0.12% chlorhexidine gluconate.
干预措施: Environmental Decontamination (Behavioral)
Treatment
Subjects are treated with one oral antibiotic, one topical antibiotic, an oral rinse, and instructed to use environmental decontamination techniques.
Trimethoprim Sulfamethoxazole (TMP/SMX) is the primary oral antibiotic to be used. Subjects with allergy or intolerance to TMP_SMX will use minocycline as an alternative antibiotic. Topical antibiotics are nasal Mupirocin, and the oral rinse/gurgle with 0.12% chlorhexidine gluconate.
干预措施: Chlorhexidine Gluconate (Drug)
Treatment
Subjects are treated with one oral antibiotic, one topical antibiotic, an oral rinse, and instructed to use environmental decontamination techniques.
Trimethoprim Sulfamethoxazole (TMP/SMX) is the primary oral antibiotic to be used. Subjects with allergy or intolerance to TMP_SMX will use minocycline as an alternative antibiotic. Topical antibiotics are nasal Mupirocin, and the oral rinse/gurgle with 0.12% chlorhexidine gluconate.
干预措施: Minocycline (Drug)
Treatment
Subjects are treated with one oral antibiotic, one topical antibiotic, an oral rinse, and instructed to use environmental decontamination techniques.
Trimethoprim Sulfamethoxazole (TMP/SMX) is the primary oral antibiotic to be used. Subjects with allergy or intolerance to TMP_SMX will use minocycline as an alternative antibiotic. Topical antibiotics are nasal Mupirocin, and the oral rinse/gurgle with 0.12% chlorhexidine gluconate.
干预措施: Mupirocin (Drug)
结局指标
主要结局
Proportion of STAR-TER subjects with a negative MRSA culture at Day 28 vs. observational arm of historic STAR-Too trial
时间窗: Day 28
Descriptive summary with corresponding 95% confidence interval.
Proportion of STAR-TER Participants With a Positive MRSA Culture at Day 28 vs. Observational Arm of Historic STAR-Too Trial
时间窗: Day 28
Descriptive summary with corresponding 95% confidence interval.
次要结局
- Proportion of subjects with a protocol-defined pulmonary exacerbation between Baseline and Day 28 treated with antibiotics active against MRSA(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(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(Period ranging from start of Baseline and continuing through Month 6)
- Time to protocol-defined pulmonary exacerbation over the six-month study(Period ranging from start of Baseline and continuing through Month 6)
- Number of protocol-defined pulmonary exacerbations over the six-month study(Period ranging from start of Baseline and continuing through Month 6)
- MRSA Culture Status(Day 56)
- Proportion of subjects with >80% compliance for study drug during the first 28 days(Day 28)
- Proportion With a Negative Culture for MRSA at Day 56(Day 56)
- Proportion With >80% Compliance for Study Drug During the First 28 Days(Day 28)
- Proportion With a Protocol-defined Pulmonary Exacerbation Between Baseline and Day 28 Treated With Antibiotics Active Against MRSA(Period ranging from start of Baseline and continuing through Day 28)
- Proportion 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(Period ranging from start of Baseline and continuing through Day 28)
- Proportion of Subjects Treated With Oral, Inhaled, or IV Antibiotics Over the Six-month Study(Period ranging from start of Baseline and continuing through Month 6)
- Time to Protocol-defined Pulmonary Exacerbation Over the Six-month Study(Period ranging from start of Baseline and continuing through Month 6)
- Number of Protocol-defined Pulmonary Exacerbations Across All Participants Over the Six-month Study(Period ranging from start of Baseline and continuing through Month 6)