A Multicenter, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Single-Dose IV Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection (SOLO I)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 968
- 试验地点
- 1
- 主要终点
- Cessation Of Spread Or Reduction In Size Of Baseline Lesion, Absence Of Fever, And No Rescue Antibiotic Medication At Early Clinical Evaluation (ECE) (48 To 72 Hours)
研究概览
简要总结
The purpose of this Phase 3 trial was to evaluate the efficacy, safety, and tolerability of oritavancin in acute bacterial skin and skin structure infections (ABSSSIs), including those caused by methicillin-resistant staphylococcus aureus (MRSA), and to evaluate the potential economic benefit of oritavancin administered as a single 1200-milligram (mg) intravenous (IV) dose.
详细描述
This was a Phase 3, multicenter, randomized, double-blind, parallel, comparative efficacy and safety study of single-dose IV oritavancin/IV placebo versus IV vancomycin for 7 to 10 days in adults with ABSSSI suspected or proven to be caused by gram-positive pathogens. Approximately 960 participants were to be randomized at 100 centers globally.
In addition, this study characterized the pharmacokinetics (PK) and PK/pharmacodynamics (PD) properties of a single 1200-mg IV dose of oritavancin and evaluated the potential health economic benefits offered by this dosing strategy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants were included in the study if they met all of the following inclusion criteria:
- •Males or females ≥18 years old
- •Diagnosis of ABSSSI suspected or confirmed to be caused by a gram-positive pathogen requiring at least 7 days of IV therapy
- •An ABSSSI included 1 of the following infections: wound infections, cellulitis/erysipelas, major cutaneous abscess
- •ABSSSI must have presented with at least 2 local signs and symptoms and at least 1 sign of systemic inflammation (unless >70 years of age).
- •Able to give informed consent and willing to comply with all required study procedures
排除标准
- •Participants were excluded from the study if any of the following exclusion criteria applied prior to randomization:
- •Prior systemic or topical antibacterial therapy with activity against suspected or proven gram-positive pathogens within the preceding 14 days unless:
- •The causative gram-positive pathogen(s) isolated from the ABSSSI site was/were resistant in vitro to the antibacterial(s) that was/were administered with documented clinical progression.
- •Documented failure to previous ABSSSI antibiotic therapy was available. Documentation of treatment failure must have been recorded.
- •Participant received a single dose of a short-acting antibacterial therapy 3 or more days before randomization.
- •Infections associated with, or in close proximity to, a prosthetic device
- •Severe sepsis or refractory shock
- •Known or suspected bacteremia at time of Screening
- •ABSSSI due to or associated with any of the following:
- •Infections suspected or documented to be caused by gram-negative pathogens
- •Wound infections (surgical or traumatic) and abscesses with only gram-negative pathogens
- •Diabetic foot infections
- •Concomitant infection at another site not including a secondary ABSSSI lesion
- •Infected burns
- •A primary infection secondary to a pre-existing skin disease with associated inflammatory changes
- •Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease
- •Any evolving necrotizing process gangrene or infection suspected or proven to be caused by Clostridium species
- •Infections known to be caused by a gram-positive organism with a vancomycin minimum inhibitory concentration >2 micrograms/milliliter or clinically failing prior therapy with glycopeptides
- •Catheter site infections
- •Allergy or intolerance to aztreonam or metronidazole in a participant with suspected or proven polymicrobial wound infection involving gram-negative and/or anaerobic bacteria
- •Was currently receiving chronic systemic immunosuppressive therapy
- •Acquired immunodeficiency syndrome with cluster of differentiation 4 count <200 cells/cubic millimeter
- •Neutropenia
- •Significant or life-threatening condition that would confound or interfere with the assessment of the ABSSSI
- •Women who were pregnant or nursing
- •History of immune-related hypersensitivity reaction to glycopeptides
- •Participants that required anticoagulant monitoring with an activated partial thromboplastin time
- •Contraindication to vancomycin
- •Participants unwilling to forego blood and/or blood product donation
- •Treatment with investigational medicinal product within 30 days before enrollment and for the duration of the study
- •Investigational device present, or removed <30 days before enrollment, or presence of device-related infection
- •Participants unlikely to adhere to the protocol, comply with study drug administration, or complete the clinical study
- •Severe hepatic disease
- •Presence of hyperuricemia
- •Unwilling to refrain from chronic use of any medication with antipyretic properties
研究组 & 干预措施
Single-Dose IV Oritavancin Diphosphate
干预措施: Single-Dose IV Oritavancin Diphosphate (Drug)
Single-Dose IV Oritavancin Diphosphate
干预措施: Placebo (Drug)
IV Vancomycin
干预措施: IV Vancomycin (Drug)
结局指标
主要结局
Cessation Of Spread Or Reduction In Size Of Baseline Lesion, Absence Of Fever, And No Rescue Antibiotic Medication At Early Clinical Evaluation (ECE) (48 To 72 Hours)
时间窗: 48-72 hours after the initiation of study therapy
Clinical response at the ECE visit (48-72 hours following initiation of study drug administration). Early clinical response was defined as a composite outcome based on cessation of spreading or reduction in the size of baseline lesion, absence of fever and no rescue antibiotic medication. A participant was classified as "success" if all of the following were met: cessation of spread or reduction of the lesion (defined as cessation of spread of the redness, edema, and/or induration or reduction in size \[length, width, and area\] of the redness, edema, and/or induration such that the size of the lesion was less than or equal to the size at baseline); resolution (absence) of fever (temperature \<37.7°Celsius at the last 3 consecutive recordings by the same route of administration taken 4 times per day, for example every 6 hours between 48 and 72 hours); no rescue antibiotic medication.
次要结局
- Number Of Participants With A Lesion Size Reduction ≥20% From Baseline At ECE(48-72 hours after the initiation of study therapy)
- Investigator Assessed Clinical Cure Of Treatment With Single-dose IV Oritavancin Compared With IV Vancomycin For 7 To 10 Days At Post-therapy Evaluation (Key Secondary Endpoint)(7-14 days after end of therapy)