Phase 1/2 Trial of Ceftaroline for the Treatment of Hematogenously Acquired Staphylococcus Aureus Osteomyelitis in Children
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to Adverse Events (AEs)
研究概览
简要总结
This research study is looking at an antibiotic medicine, Ceftaroline Fosamil (Ceftaroline), which fights infections like the one the subject has. Ceftaroline is effective against S.aureus germs including those that are called Methicillin Resistant Staphylococcus aureus (MRSA.)
Ceftaroline has been approved by the U.S. Food and Drug Administration (FDA) for use in adults and children with Community-Acquired Bacterial Pneumonia [a type of lung infection] and Acute Bacterial Skin and Skin Structure Infections. Ceftaroline is not yet approved for treatment in subjects with hematogenous osteomyelitis, therefore, the use of Ceftaroline in this research study is considered "investigational".
The goal of this research study is to find out what side effects there may be when children are taking Ceftaroline and to study how effective Ceftaroline is in treating bone infections due to Staphylococcus aureus in children. The investigators are also studying what the body does to the study drug, Ceftaroline, and if the doses the investigators use result in blood levels that the investigators think are going to be effective against bone infections in children. This is called pharmacokinetics (PK).
详细描述
This is a Phase 1/2, open-label, single-center study to determine safety and tolerability of Ceftaroline in pediatric subjects 1 to 17 years of age (inclusive) with signs and symptoms of acute hematogenous osteomyelitis at the end of intravenous therapy. After informed consent/assent is obtained, Ceftaroline will be administered intravenously. After the subject has been afebrile for at least 48 hours, has negative blood cultures, is clearly improving in general, is able to eat and drink, and is able to use or move the involved extremity, the subject may be switched to oral antibiotic administration.
The duration of subject participation from signing the informed consent form will be up to 14 months [(includes screening period (1 Day), study IV drug administration (approximately 2-14 Days), Standard of Care Oral Drug Administration (4-5 weeks) (the total maximum treatment period is typically 6 weeks), and a follow-up visit 12 months after the last dose of study drug)]. Baseline assessments for study eligibility will occur within 24 hours before the first dose of study drug. A minimum of 2 days (48 hours) of study drug administration is required.
Some of the tests and procedures completed during this study may be part of regular care for the subject's condition. Some tests and procedures will be done only for study purposes. Some regular procedures may also be completed more often as part of the research study.
Study assessments:
- Past and Current Medical History: A detailed review of the subject's medical history, including demographics, concomitant medication review, medical/surgical history will be performed.
- Vital Signs: Weight, height, blood pressure, pulse rate, and body temperature, will be recorded.
- Physical Exam: Physical exam will include, evaluation of subject's overall health, examination site of infection, and assessment of subject's ability to move affected limb.
- Safety Laboratory Assessments: Routine laboratory monitoring including liver function tests will be done 24 hours prior to enrollment and weekly during Ceftaroline treatment, and the completion of Ceftaroline treatment and at the follow-up visit. Isolate susceptibility testing will be done at baseline visit.
- Pregnancy testing: For females of child-bearing potential, urine pregnancy will be performed prior to and after completing antibiotic treatment.
- Pharmacokinetics Assessment: One PK blood sample will be obtained from all subjects who receive Ceftaroline fosamil.
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
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent in writing from parent(s) or other legally acceptable representative(s) and assent from subject (if appropriate according to local requirements)
- •Male or female 1 to 17 years of age, inclusive.
- •Suspected hematogenous S.aureus osteomyelitis in a large bone (upper or lower extremities, pelvis) based on clinical findings and radiology results.
- •One to three site(s) of osteomyelitis with expectation that transition to oral antibiotics from IV therapy will be likely prior to discharge to complete antibiotic therapy. The second or third site might be contiguous like a proximal tibia and distal femur but could also be at sites unrelated such as a distal femur and pelvic bone.
- •Female subjects who have reached menarche must have a negative urine pregnancy test.
- •Female subjects who have reached menarche and are sexually active must be willing to practice sexual abstinence or dual methods of birth control during treatment and for at least 28 days after the last dose of any study drug.
- •Sufficient IV access to receive medication.
排除标准
- •Received more than 24 hours of IV antibiotics prior to enrollment
- •More than one bone infected
- •Disseminated infection or is admitted to the pediatric intensive care unit
- •Underlying condition (excludes mild eczema or reactive airways disease)
- •Suspected venous thrombosis or concern for endocarditis
- •Requirement for other reasons for another antibiotic potentially active against organisms commonly causing osteomyelitis in children.
- •Creatinine clearance less than 50 mL/min/1.73m2 (calculated by the Schwartz formula)
- •Liver transaminases greater than 3 times the upper limit of normal
- •Neutropenia (less than 500 neutrophils/mm^3
- •Thrombocytopenia (less than 50,000 platelets/mm^3)
- •Females who are currently pregnant or breast feeding
- •Hypersensitivity reaction to any Beta-lactam antibiotic
- •Has had an allergic reaction to ceftaroline in the past
研究组 & 干预措施
Ceftaroline Fosamil
IV Ceftaroline fosamil 15 mg/kg (or 600 mg if > 40 kg) infused over 120 (± 10) minutes q8h (± 1 hour). The dose may vary with age.
干预措施: Ceftaroline Fosamil (Drug)
结局指标
主要结局
Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to Adverse Events (AEs)
时间窗: Predose and every 8 hours up to a maximum of 14 days for ceftaroline administration.
Evaluate the safety of Ceftaroline in pediatric subjects 1 to 17 years of age (inclusive) with acute hematogenous osteomyelitis at the end of intravenous therapy.
次要结局
- Clinical Outcome at the Completion of Total Therapy (IV Ceftaroline Plus Oral Antibiotics)(8 weeks)
- Clinical Response at the Conclusion of IV Ceftaroline(2 weeks)
- Clinical Outcome During the One Year Follow-up Period After End of Antibiotic Treatment Which is Approximately 14 Months After Enrollment.(14 months)
- Proportion of Participants With Plasma Levels of Ceftaroline That Exceeds 1 μg/mL for Over 60% of a Dosing Interval(Blood for ceftaroline levels could be obtained once on study day 2 through day 5 post infusion of a dose of ceftaroline.)
研究者
Sheldon Kaplan
Professor
Baylor College of Medicine