A Phase 3, Double-blinded, Randomized, Comparator Trial of the Safety and Efficacy of a Single Dose of Dalbavancin to Twice Daily Linezolid for the Treatment of Community Acquired Bacterial Pneumonia
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Treatment Response of CABP Symptoms
研究概览
简要总结
This study will be a double-blind, randomized, multicenter trial to assess the safety and efficacy of a single 1500 mg IV dose of dalbavancin plus a single 500 mg IV dose of azithromycin in comparison to an approved antibiotic regimen of linezolid 600 mg every 12 hours for 10-14 days plus a single 500 mg IV dose of azithromycin for the treatment of Community Acquired Bacterial Pneumonia.
详细描述
This study will be a double-blind, randomized, multicenter trial to assess the safety and efficacy of a single 1500 mg IV dose of dalbavancin plus a single 500 mg IV dose of azithromycin in comparison to an approved antibiotic regimen of linezolid 600 mg every 12 hours for 10-14 days plus a single 500 mg IV dose of azithromycin for the treatment of CABP. Adult patients who meet all inclusion and none of the exclusion criteria will be randomized to one of the two treatment arms. Dosing will commence on Day 1, and all patients will receive a minimum of 10 days of therapy. Patients will be assessed on Day 1, Day 4-5, Day 7, Day 14 (End of Therapy, EOT), and Day 28 (Follow up).
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
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 to 85, inclusive
- •Has given written, informed consent
- •Has acute illness with onset within previous 7 days
- •Has at least 2 of the following symptoms:
- •Difficulty breathing or shortness of breath
- •Production of purulent sputum
- •Pleuritic chest pain
- •Has at least 2 vital sign abnormalities:
- •Fever (> 38°C or < 35°C)
- •Hypotension (systolic BP < 90 mm Hg)
- •Tachycardia (> 100 beats /min)
- •Tachypnea (> 24 breaths /min)
- •Has at least one other clinical or laboratory abnormalities:
- •Hypoxemia (room air SaO2 < 90% )
- •Clinical evidence of pulmonary consolidation
- •Elevated WBC count or neutropenia (> 12,000/mm3 or < 4,000/mm3)
- •Has new lobar or multi-lobar infiltrates on chest radiograph
- •Has CURB-65 risk category 1 to
- •Patients with CURB-65 risk category 1 will be limited to 20% of the total patient population
排除标准
- •Contra-indication to the administration of any of the study treatments, such as hypersensitivity to any of the glycopeptide agents, beta-lactam agents, linezolid or macrolide antibiotics, or current or recent (within 2 weeks) use of MAO inhibitors or serotonergic antidepressants (within 5 weeks for fluoxetine) (see Section 5.5.1)
- •Has received antibiotic therapy in the 4 days prior to screening, with the following exception: up to 25% of patients may have received a single dose of a short acting (half life < 8 hours) antibiotic
- •Has aspiration pneumonia
- •Has hospital acquired or ventilator associated pneumonia, or healthcare associated pneumonia, or 2 or more days in hospital in the previous 90 days
- •Has cystic fibrosis or known or suspected Pneumocystis pneumonia or known or suspected active tuberculosis
- •Females of child-bearing potential who are unable to take adequate contraceptive precautions, have a positive pregnancy result within 24 hours prior to study entry, are known to be pregnant, or are currently breastfeeding an infant
- •Has primary or metastatic lung cancer
- •Has known bronchial obstruction or a history of post-obstructive pneumonia
- •Requires admission to ICU at baseline
- •Has empyema requiring drainage
- •Infection due to an organism known prior to study entry to be resistant to either treatment regimen
- •Has known or suspected infection due solely to an atypical pathogen such as Mycoplasma sp., Chlamydia sp. or Legionella sp. or positive Legionella urinary antigen at baseline
- •Absolute neutrophil count < 500 cells/mm3
- •Known or suspected human immunodeficiency virus (HIV) infected patients with a CD4 cell count < 200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count
- •Patients with a recent bone marrow transplant (in post-transplant hospital stay)
- •Patients receiving oral steroids > 40 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation
- •Patients with a rapidly fatal illness, who are not expected to survive for 3 months
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
- •Has participated in another trial of an investigational pharmaceutical product in the 30 days prior to enrollment
- •Prior participation in this trial.
研究组 & 干预措施
Dalbavancin
Dalbavancin randomized subjects will receive one dose of dalbavancin 1500 mg IV over 30 minutes on Day 1 plus azithromycin 500 mg IV on Day 1. Dalbavancin dose will be adjusted for subjects with significant renal insufficiency who are not receiving regular hemodialysis. All patients in the dalbavancin group will receive placebo linezolid infusions or tablets to maintain the blinding. Dalbavancin dose will be adjusted for subjects with significant renal insufficiency who are not receiving regular hemodialysis
干预措施: Dalbavancin (Drug)
Linezolid
Linezolid randomized subjects will receive linezolid 600 mg every 12 hours for a minimum of 10 days, and a maximum of 14 days. All patients will receive at least one IV dose of linezolid initially plus azithromycin 500 mg IV only on Day 1. Subjects then may then be switched to oral linezolid at the discretion of the investigator, if clinical improvement in the signs and symptoms of pneumonia is observed, to complete the 10-14 day course of therapy,. No dose adjustment is required for renal insufficiency.
干预措施: Linezolid (Drug)
Linezold Placebo IV and Oral Capsules
Dalbavancin randomized subjects after the 1st dose on Day 1 will receive placebo linezolid every 12 hours for a minimum of 10 days and a maximum of 14 days. Dalbavancin randomized subjects may be switched to oral linezolid placebo therapy to complete the 10-14 day course of therapy.
干预措施: Linezolid Placebo (Drug)
Azithromycin
Dalbavancin and linezolid randomized subjects on Day 1, 1st dose will also receive 500 mg of IV azithromycin
干预措施: Azithromycin (Drug)
结局指标
主要结局
Treatment Response of CABP Symptoms
时间窗: Change from Baseline to 72-120 hours after randomization
Compare the efficacy of a single 1500 mg dose of intravenous dalbavancin plus azithromycin to the comparator regimen (linezolid plus azithromycin). Response will be based on resolution of symptoms; including chest pain, shortness of breath (difficulty breathing), frequency/severity of cough and amount of sputum production. Each of these symptoms will be assessed on a 4 point scale (absent, mild, moderate or severe). A patient will be defined as a clinical responder if there is at least a 1 point improvement in 2 or more of these symptoms at 72-120 hours after randomization compared to baseline.
次要结局
- Efficacy of dalbavancin to the comparator regimen(Change from baseline to 72-120 hours after randomization, Day 14 and Day 28)
- Safety Analysis(Safety will be assessed at all time-points through Day 28)