Persistent MRSA Eradication Protocol (PMEP)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Number of Patients MRSA Free by Induced Sputum Respiratory Tract Culture
研究概览
简要总结
The prevalence of methicillin resistant Staphylococcus aureus (MRSA) respiratory infection in Cystic Fibrosis (CF) has increased dramatically over the last decade. Evidence suggests that persistent infection with MRSA may result in an increased rate of decline in Forced Expiratory Volume (FEV)1 and shortened survival. Currently there are no conclusive studies demonstrating an effective aggressive treatment protocol for persistent MRSA respiratory infection in CF. Data demonstrating an effective and safe method of clearing persistent MRSA infection are needed.
The purpose of this study is to evaluate the safety and efficacy of a 28-day course of vancomycin for inhalation, 250 mg twice a day, (in combination with oral antibiotics) in eliminating MRSA from the respiratory tract of individuals with CF and persistent MRSA infection. Subjects will be assigned in a 1:1 ratio to either vancomycin for inhalation (250 mg twice a day) or taste matched placebo and will be followed for 3 additional months. In addition, both groups will receive oral rifampin, a second oral antibiotic (TMP-SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Forty patients with persistent respiratory tract MRSA infection will be enrolled in this trial.
详细描述
Primary Objectives
The primary objectives of this trial are to:
- Determine the efficacy of an aggressive treatment protocol in eradicating persistent MRSA infection in individuals with CF.
- Determine the safety of an aggressive treatment protocol in eradicating persistent MRSA infection in individuals with CF.
Secondary Objectives
The secondary objectives of this trial are to:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 12 years of age.
- •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 Nasal Potential Difference (NPD), and one or more clinical features consistent with the CF phenotype.
- •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.
- •Two positive MRSA respiratory cultures in the last two years at least six months apart, plus a positive MRSA respiratory culture at Screening Visit and Run-in (Day -14) Visit.
- •At least 50% of respiratory cultures from the time of the first MRSA culture (in the last two years) have been positive for MRSA.
- •Forced Expiratory Volume (FEV)1 > 40% of predicted normal for age, gender, and height at Screening, for subjects 18 years of age or older..
- •FEV1> 60% of predicted normal for age, gender, and height at Screening, for subjects 12--17 years of old.
- •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
排除标准
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or change in routine therapy (including antibiotics) for pulmonary disease within 42 days of the Day 1 Visit (2 weeks prior to Screening visit).
- •Individuals on chronic continuous inhaled antibiotics without interruption who are not willing to substitute vancomycin or placebo for their scheduled inhaled antibiotic during days 0-28 of the study (every other month inhaled antibiotics are acceptable)
- •Use of oral or inhaled anti-MRSA drugs within two weeks of the Screening Visit.
- •History of intolerance to inhaled vancomycin or inhaled albuterol.
- •History of intolerance to rifampin or both TMP/SMX and doxycycline.
- •Resistance to rifampin or both TMP/SMX and doxycycline at Screening.
- •Resistance to vancomycin at Screening.
- •Abnormal renal function, defined as creatinine clearance < 50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening.
- •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.
- •Serum hematology or chemistry results which in the judgment of the investigator would interfere with completion of the study.
- •History of or listed for solid organ or hematological transplantation
- •History of sputum culture with non-tuberculous Mycobacteria in the last 6 months.
- •History of sputum culture with Burkholderia Cepacia in the last year.
- •Planned continuous use of soft contact lenses while taking rifampin and no access to glasses.
- •Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day
- •Administration of any investigational drug or device within 28 days of Screening or within 6 half-lives of the investigational drug (whichever is longer).
- •Patients on inhaled antibiotics must have been on the same regimen for the 4 months prior to screening
- •Female patients of childbearing potential who are pregnant or lactating, or plan on becoming pregnant
- •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.
研究组 & 干预措施
Inhaled Vanc and Oral Abx
In the experimental arm CF participants are randomized to 28 days of inhaled sterile vancomycin (250 mg twice a day) as well as 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Inhaled Vancomycin (Drug)
Inhaled Vanc and Oral Abx
In the experimental arm CF participants are randomized to 28 days of inhaled sterile vancomycin (250 mg twice a day) as well as 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Rifampin (Drug)
Inhaled Vanc and Oral Abx
In the experimental arm CF participants are randomized to 28 days of inhaled sterile vancomycin (250 mg twice a day) as well as 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Trimethoprim/Sulfamethoxazole (TMP/SMX) (Drug)
Inhaled Vanc and Oral Abx
In the experimental arm CF participants are randomized to 28 days of inhaled sterile vancomycin (250 mg twice a day) as well as 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Doxycycline (Drug)
Inhaled Vanc and Oral Abx
In the experimental arm CF participants are randomized to 28 days of inhaled sterile vancomycin (250 mg twice a day) as well as 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Mupirocin Intranasal Creme (Drug)
Inhaled Vanc and Oral Abx
In the experimental arm CF participants are randomized to 28 days of inhaled sterile vancomycin (250 mg twice a day) as well as 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: 4% chlorhexidine gluconate liquid skin cleanser (Drug)
Inhaled Placebo and Oral Abx
In the active comparator arm CF participants are randomized to 28 days of inhaled sterile placebo (saline) and are treated with 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Placebo (Sterile Water) (Drug)
Inhaled Placebo and Oral Abx
In the active comparator arm CF participants are randomized to 28 days of inhaled sterile placebo (saline) and are treated with 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Rifampin (Drug)
Inhaled Placebo and Oral Abx
In the active comparator arm CF participants are randomized to 28 days of inhaled sterile placebo (saline) and are treated with 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Trimethoprim/Sulfamethoxazole (TMP/SMX) (Drug)
Inhaled Placebo and Oral Abx
In the active comparator arm CF participants are randomized to 28 days of inhaled sterile placebo (saline) and are treated with 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Doxycycline (Drug)
Inhaled Placebo and Oral Abx
In the active comparator arm CF participants are randomized to 28 days of inhaled sterile placebo (saline) and are treated with 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: Mupirocin Intranasal Creme (Drug)
Inhaled Placebo and Oral Abx
In the active comparator arm CF participants are randomized to 28 days of inhaled sterile placebo (saline) and are treated with 28 days of oral/skin antibiotics targeted to aggressively treat MRSA infection: oral rifampin, a second oral antibiotic (TMP/SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes. Patients will be followed for 3 months after completion of the treatment protocol.
干预措施: 4% chlorhexidine gluconate liquid skin cleanser (Drug)
结局指标
主要结局
Number of Patients MRSA Free by Induced Sputum Respiratory Tract Culture
时间窗: Day 58 (Visit 5), approximately 1 month after completion of the MRSA treatment protocol
The hypothesis for our primary outcome is that the aggressive treatment arm will result in significantly greater eradication of persistent MRSA from the respiratory tract of CF adolescents and adults on day 58 (1 month after completion of therapy) compared to the placebo/standard treatment arm. Our primary outcome will be comparing the proportion of CF patients in the treatment arm who have a negative induced sputum MRSA culture at Day 58 to the proportion of patients in the placebo arm who have a negative induced sputum MRSA culture at Day 58.
次要结局
- Change in Forced Expiratory Volume (FEV1)% Predicted From Baseline to Day 58(Baseline, Day 58)
- Time to First CF Exacerbation(Day 1 to Day 118)
- Total Number of Pulmonary Exacerbations(Days 58 and 118)
- Change in Patient Reported Quality of Life (CFQ-R)(Respiratory)(Days 29 and 58)
- Time to First Anti-MRSA Antibiotics (After Treatment Period)(Completion of Study Drug to Day 118)
- Percentage of Patients MRSA Free by Induced Sputum Respiratory Tract Culture(Day 29)
- Development of Antibiotic Resistance(Day 58 (Visit 5))
- Change if FEV1% Predicted From Screening(Days 29, 58, and 118)