Omadacycline Versus Standard-of-Care Oral Antibiotic Treatment for Bone and Joint Infections: An Open-Label, Non- Inferiority, Randomized, Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- To compare the treatment success, as defined by lack of definite treatment failure, of omadacycline versus standard of care (SOC) antibiotics for bone and joint infections (BJIs) two weeks after therapy completion.
研究概览
简要总结
The study design is a randomized, open-label, clinical trial of omadacycline vs Standard of Care (SOC) antibiotics for bone and join infection (BJI) treatment. Study participants will have their BJI regimen chosen by their treating physicians, (typically Infectious Diseases for hardware and prosthetic joint infections, or multidisciplinary Limb Salvage team for diabetic foot infections) prior to enrollment. Then participants will be randomized to an omadacycline-containing regimen versus the a priori chosen SOC regimen. Participants must require between 4 and 12 weeks of therapy for their BJI. The exact duration of therapy will be decided by the participants' treating physician. At 12 weeks, if the treating physician wishes to extend therapy, participants receiving omadacycline will be transitioned to other SOC antibiotics.
Once enrolled, participants will be followed via in-person clinic visits at the following intervals: weeks 0, 2, 4, 8, and 12. A final in-person visit will occur 2 weeks post-treatment completion. A phone survey will occur 3 months post-treatment completion. Participants in the SOC group will follow the same schedule.
Oral once-daily dosing options for S. aureus and Coagulase negative Staphylococcus are essentially non-existent. Thus, omadacycline possesses a novel and advantageous option for BJI treatment. Its convenient dosing regimen will almost certainly be associated with improved adherence, and higher adherence may, in turn, improve clinical outcome. Investigators hypothesize that omadacycline will be a well-tolerated and efficacious oral antibiotic for BJIs and will be associated with improved adherence compared with standard of care oral antibiotics. Investigators believe omadacycline addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for use as a prolonged therapy for BJIs. To this aim, investigators will perform a randomized, open-label clinical trial of omadacycline to SOC antibiotics for BJIs.
详细描述
The design of this study is a prospective, open-label, randomized clinical trial of omadacycline vs SOC antibiotics for the treatment of BJIs. We will follow subjects for between 16 and 24 weeks, depending on the length of their antibiotic treatment, for the purpose of determining tolerability, safety, and treatment success of prolonged use (> 4 weeks) of omadacycline in the treatment of BJIs. Subjects will be enrolled regardless of race, ethnicity, or gender (as long as they are within 18 - 85 years of age).
Subjects will be given omadacycline-containing regimen versus SOC. Omadacycline will be administered 300 mg orally daily without loading dose duration of therapy of between 4 and 12 weeks. The exact duration of therapy will be decided by the subject's treating physician. In other words, the primary/consulting physician who is managing the treatment of the subject's bone and joint infection will be the one who decides the length of the antibiotic treatment.
Safety and tolerability of omadacycline through this study will be guaranteed for 12 weeks. At 12 weeks, if the treating physician wishes to extend therapy, subjects receiving omadacycline will be transitioned to other SOC antibiotics. Medications will be provided by the Investigational Drug Service (IDS) on The Lundquist Institute/Harbor-UCLA campus, which supplies all research related medications to study subjects at our center.
Subjects will be enrolled as outpatients or as inpatients when discharge is expected in the near future (< 1 week). Drs. Loren Miller and/or Amy Kang, the Co-Principal Investigators, will advise the hospital staff of the study and seek their assistance in identifying and notifying the study staff of possible subjects who have presented to the Emergency Department, inpatient units, or outpatient clinic with BJI.
Our primary endpoint is treatment success 2-weeks after therapy completion. We hypothesize that omadacycline will be non-inferior to SOC antibiotics for BJI treatment. For descriptive purposes, treatment outcome will be further sub-categorized as one of the following outcomes: treatment success, failure due (or probably due) to medication, and failure not due (or unlikely due) to medication (e.g., surgical issues such as inadequate source control). For our primary analysis, we will dichotomize outcomes to treatment success and treatment failure. Treatment success will be defined as the lack of definite treatment failure. Treatment failure will be defined using the definition utilized in the OVIVA trial. Specifically, definite failure will be defined as the presence of at least one clinical criterion (draining sinus tract arising from bone or prosthesis or the presence of frank pus adjacent to bone or prosthesis), microbiologic criterion (phenotypically indistinguishable bacteria isolated from two or more deep-tissue samples or a pathogenic organism from a single closed aspirate or biopsy), or histologic criterion (presence of characteristic inflammatory infiltrate or microorganisms).
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
- None
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
- •Diagnosis of BJI or probable BJI as defined clinically using radiologic (e.g., MRI), surgical (e.g., intra-operative findings), and/or clinical (e.g., probe to bone) definitions
- •BJI caused by or suspected to be caused by organisms that omadacycline is expected to be active against
- •Planned treatment duration of 4-12 weeks
- •Plans to continue or initiate treatment in outpatient setting
- •Limited planned course of antibiotics (i.e., no indefinite treatment plans for chronic suppression)
- •Able to take oral medications
- •Able to come to the research clinic for study follow-up visits for the study period
- •If a woman is of childbearing potential, she must consistently use two acceptable methods of contraception (IUD, injectable contraceptive, birth control patch, OCP, barrier method, abstinence) from baseline through the course of antibiotics (4-12 weeks). If a male patient's sexual partner is of childbearing potential, the male patient must acknowledge that they will consistently use an acceptable method of contraception as defined above from baseline through the course of antibiotics (4-12 weeks)
排除标准
- •Pregnancy or breast feeding. Women of childbearing potential must have a negative urine or serum pregnancy test result within 1 day prior to initiation of study drug
- •Hypersensitivity to tetracycline-class antibiotics
- •BJI caused by fungi or mycobacteria
- •BJI complicated by endocarditis, central nervous system involvement such as subdural abscess, or any foci of metastatic infection, such as renal or splenic abscesses
- •Prosthetic joint infections that have not undergone both stages of two stages of surgical treatments (i.e., subjects are only eligible after the 2nd stage surgery has been completed and typically 6 weeks of IV therapy has been completed)
- •Hematogenous BJI prior to adequate treatment for bacteremia (i.e., subjects are only eligible after adequate IV course of bacteremia is completed and additional oral therapy is still required for infection "mop up")
- •Any medical, psychological, or social condition that, in the opinion of the Investigator, would prevent the patient from fully participating in the study or would represent a concern for study compliance or constitute a safety concern to the patient
研究组 & 干预措施
omadacycline
Omadacycline will be administered 300 mg orally daily without the loading dose. We chose to omit the loading dose given that many of the enrolled subjects would have received an IV therapy prior to omadacycline initiation and notable gastrointestinal intolerabilities (nausea/vomiting) based on Phase-3 trial data. Subjects receiving omadacycline will be counseled on appropriate timing of administration (fast for 4 hours before dosing and no food for 2 hours after dosing) in light of the known food effects on drug absorption. They will be instructed to avoid use of products containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron containing preparations such as dairy, antacids, and multivitamins for 4 hours post-dosing.
干预措施: Omadacycline Pill (Drug)
standard of care antibiotic
Standard of care as determined by primary care team
干预措施: Standard of Care (Drug)
结局指标
主要结局
To compare the treatment success, as defined by lack of definite treatment failure, of omadacycline versus standard of care (SOC) antibiotics for bone and joint infections (BJIs) two weeks after therapy completion.
时间窗: 2 weeks post-therapy
We will dichotomize outcomes to treatment success and treatment failure. Treatment success will be defined as the lack of definite treatment failure. Treatment failure will be defined using the definition utilized in the OVIVA trial. Specifically, failure will be defined as the presence of at least one clinical criterion (draining sinus tract arising from bone or prosthesis or the presence of frank pus adjacent to bone or prosthesis), microbiologic criterion (phenotypically indistinguishable bacteria isolated from two or more deep-tissue samples or a pathogenic organism from a single closed aspirate or biopsy), or histologic criterion (presence of characteristic inflammatory infiltrate or microorganisms).
次要结局
- Quantify the long term efficacy of omadacycline for BJIs, both non-hardware and hardware associated after therapy completion.(3 months post-therapy)
研究者
loren g miller
Chief, Division of Infectious Diseases
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center