A Prospective, Multicenter, Randomized, Open Label, Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Delafloxacin (Injection and Tablets) in comparison to Levofloxacin (Injection and Tablets) in patients with Severe Community Acquired Bacterial Pneumonia
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 234
- 试验地点
- 13
研究概览
简要总结
This is a prospective, multicenter, randomized, open-label, active-controlled, Phase 3 non-inferiority study to be conducted at approximately 20–30 centers across India, following approval from Regulatory Authorities and Ethics Committees.
The study evaluates the efficacy and safety of a structured intravenous (IV) to oral switch strategy using delafloxacin versus levofloxacin in adult patients with confirmed severe community-acquired pneumonia (CAP). Initial IV therapy is required to ensure rapid therapeutic levels and clinical stabilization; however, early transition to oral therapy after clinical improvement offers benefits such as reduced hospital stay, lower healthcare costs, improved patient comfort, and reduced IV catheter-related complications.
An open-label design is appropriate to support on-site clinical decision-making, particularly regarding IV-to-oral switch timing, oral tolerability, and microbiological results. In the levofloxacin arm, if methicillin-resistant Staphylococcus aureus (MRSA) is identified, predefined protocol-guided initiation of linezolid (IV and oral) will be implemented.
Following informed consent, screening assessments will be completed within 24 hours. Baseline evaluations include chest imaging within 48 hours prior to dosing, medical history, physical examination, laboratory tests, and respiratory and blood cultures within 24 hours prior to the first dose. Only subjects classified as PORT Risk Class III, IV, or V will be enrolled. Microbiological identification will be performed using rapid and/or conventional methods as per local availability. Investigator decisions regarding subject continuation will be based on clinical judgment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients of either gender with age between 18 to 65 years (both inclusive) and willing to provide written informed consent and comply with protocol requirements.
- •Evidence of acute onset of CABP before hospital-admission or within 48 hours after admission.
- •Presence of lobar, multi-lobar, or patchy parenchymal infiltrate(s) consistent with acute bacterial pneumonia on a lung imaging study within 48 hours before the first dose of study drug 4)PORT Risk Class of III, IV, or V (PSI Score greater than 70).
- •Presence of at least one risk factors for the Multi Drug Resistance organisms 6) In the opinion of the investigator, the subject must be a suitable candidate for possible I.V. to oral switch antibiotic therapy and must also be able to swallow large tablets intact without crushing 7) Women of childbearing potential must have a negative urine pregnancy test prior to Screening and Randomization and agree to use highly effective methods of contraception to prevent pregnancy from study entry till EOS 8) Male patients must have had a successful vasectomy (confirmed azoospermia) or they and their female partners should be practicing highly effective contraception throughout the study period.
- •(Contraception by female partner is not required if she is not a woman of childbearing potential) [No sperm donation is allowed during the study period].
排除标准
- •Any infection expected to require other systemic antibacterial agents in addition to study drug 2) Receipt of systemic antibiotic therapy in the 7 days before enrollment.
- •Respiratory infection confirmed or suspected to be secondary to hospital-acquired or ventilator-associated pneumonia at the time of informed consent.
- •Hospitalization for 2 or more days within 90 days prior to the onset of symptoms 5) Intubated or need mechanical ventilation or vasopressor support for septic shock or ICU care at screening visit 6) Patients on ECMO (Extracorporeal membrane oxygenation) or predicted to be on ECMO at screening visit 7) Pre-existing thrombosis or other thromboembolic events (TEEs) within 3 months before screening visit.
- •Pre-existing decompensated heart failure.
- •Known anatomical or pathological bronchial obstruction, or a history of bronchiectasis, or documented Global initiative for chronic Obstructive Lung Disease Stage 4 chronic obstructive pulmonary disease, or a history of post obstructive pneumonia 10) Severely compromised immune system, 11) Patients having significant renal impairment or hepatic impairment 12) Uncorrected hypokalemia, or known uncorrected hypomagnesemia, at the time of enrollment.
- •Ongoing treatment for seizures or untreated history of seizures 14) History of peripheral neuropathy 15) History of tendon damage disorders due to quinolone therapy 16) Known history of myasthenia gravis 17) History of post-antibiotic colitis within the last 3 months 18) Ventricular arrhythmia and or ongoing proarrhythmic conditions such as clinically significant bradycardia, acute myocardial ischemia 19) History of or diagnosed with prolonged QT syndrome, 20) Concomitant use of drugs known to prolong the QT interval, 21) Concomitant use of monoamine oxidases A or B inhibitor agents and adrenergic and serotonergic agents within 2 weeks of screening 22) Patients with known uncontrolled hypertension, pheochromocytoma, carcinoid thyrotoxicosis and rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption 23) Life expectancy of less than 3 months 24) Immediate life-threatening disease 25) Patients diagnosed with HIV, HBV, and HCV infection 26) Any underlying disease e.g. severe cardiac disease, malignancy, or psychiatric disorder that, in the opinion of the investigator, may interfere with the subject’s ability to participate in the study 27) Previous participation in any study of delafloxacin 28) Receipt of an investigational drug within 30 days of randomization 29) Women who are pregnant, nursing, or fertile and not using contraception 30) Known hypersensitivity to study medications Delafloxacin, Levofloxacin, Linezolid or to any of their excipients.
研究者
Dr Pravin Ghadge
Sun Pharma Laboratories Limited