PhagoDAIR I : A Pilot, Multicenter, Randomized, Non Comparative, Double-Blind Study of Phage Therapy in Patients with Hip or Knee Prosthetic Joint Infection due to Staphylococcus aureus Treated with DAIR and Antibiotic Therapy.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 11
- 主要终点
- Clinical control of infection defined by: no clinical signs of evolutive infection: no fever (defined by a temperature less than 38°C) due to prosthesis infection and no recurrence, neither recurrent, nor worsening pain
研究概览
简要总结
To estimate the rate of clinical control of infection due to Staphylococcus aureus of two different therapeutic regimens: DAIR + curative antibiotics therapy combined with bacteriophages or solution of NaCl 0.9%; in patients presenting a Prosthesis Joint Infection (PJI) later than 1 month after the arthroplasty, with the indication of DAIR + Suppressive Antibiotics Therapy (SAT) which will allow to calculate the sample size for future comparative studies.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Rescue Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 18 years
- •Negative pregnancy test
- •Signing a written informed consent before any study related procedures
- •Affiliated to a national social security system and / or private health insurance in compliance with the recommendations of National Law in force relating to biomedical research
- •Staphylococcus aureus monomicrobial knee or hip PJI > 1 month after prosthesis implantation with clinical signs of infection and with indication of DAIR with direct closure (if associated flap, arthrotomy must be sealed), and Suppressive Antibiotics Therapy (SAT)
- •Staphylococcus aureus only in joint fluid within 6 months before randomization or in case of relapse of infection under antibiotics therapy after a DAIR performed within 6 months before pre-inclusion visit
- •Without preoperative diagnosis of superinfection due to another pathogen if treatment is administered at the end of the DAIR
- •Without diagnosis of superinfection due to another pathogen identified within 72h after a bacteriological sample performed during a DAIR if treatment is administered 14±2 days after a DAIR.
- •Displaying the susceptibility of the strain to at least one of the phages.
- •Patient with a life expectancy of 2 years and more as determined by the principal investigator
- •Females of childbearing potential/Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable effective method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices, condom) for 1 month after the last study drug administration
- •Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months)
排除标准
- •Early Staphylococcus aureus Prosthesis Joint infection ( < 1 month after the prosthesis implantation)
- •Medical history which in the opinion of the investigator would mean that the patient is unsuitable for participation in the study
- •Patient who, in the judgment of the Investigator, is likely to be noncompliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development
- •Currently in exclusion period from a previous study
- •Concomitant participation to another interventional clinical trial or previous participation with active drug levels still present, i.e. the last medication intake is less than 4 half-lives ago
- •Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period and up to 1 month after the last administration of study drug
- •Women/Men refusing to use an acceptable effective contraception during 1 month after the last administration of study drug
- •No possibility of contact in case of emergency
- •Minors, persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care and persons admitted to a health or social institution, to adult patient under legal protection or unable to express consent.
- •Other germ found in culture of joint fluid sample
- •Displaying no susceptibility of the strain to anti-Staphylococcus aureus bacteriophages
- •Patients with ASA score ≥ 4
- •Severe sepsis or Septic shock or hemodynamic instability
- •Patients with an indication to prosthesis replacement or amputation
- •Immunosuppressed patients
- •Known allergic reactions to components of phages products
- •Relapse between DAIR and treatment administration planned 14±2 days after a DAIR
结局指标
主要结局
Clinical control of infection defined by: no clinical signs of evolutive infection: no fever (defined by a temperature less than 38°C) due to prosthesis infection and no recurrence, neither recurrent, nor worsening pain
Clinical control of infection defined by: no clinical signs of evolutive infection: no fever (defined by a temperature less than 38°C) due to prosthesis infection and no recurrence, neither recurrent, nor worsening pain
Peri articular Inflammatory and infectious Clinical signs will be collected : No local post surgical recurrence or worsening of local articular swelling / No unusual aspect of scar as erythema or abnormal flow or a fistula or inflammatory or local necrosis or no healing
Peri articular Inflammatory and infectious Clinical signs will be collected : No local post surgical recurrence or worsening of local articular swelling / No unusual aspect of scar as erythema or abnormal flow or a fistula or inflammatory or local necrosis or no healing
No new surgical procedure requested and no Staphylococcus aureus detected
No new surgical procedure requested and no Staphylococcus aureus detected
次要结局
- Safety parameters: adverse events, physical examination, biological tests as hematology and biochemistry during the whole study
- Initial activity of phages: active bacteriophages (PP1493 and/or PP1815) in regard of the clinical outcome (infection control or relapse) of patients
- Clinical control of the infection (as described in primary endpoint) for superinfected patients (other species isolated during the surgical procedure)
- In case of failure, aspiration of joint fluid at time of failure for microbiological test and identification of Staphylococcus aureus strain: antibiogram
- Duration of hospitalization
- Questionnaire EQ-5D-5L for quality of life at each visit (except D14±1 and D28±2)
- Evaluation of joint function with: - Knee: KOOS 12-Knee Survey - Hip: HOOS 12-Hip Survey
- Clinical control of the infection (as described in primary endpoint)
- To check potential appearance of abnormal loosening (border with shifting of the prosthesis) or an abnormal periprosthetic border
- In case of rescue treatment: clinical infection control after the first ultra guided injection, safety parameters, pharmacokinetics, bacteriological and immunological tests
研究者
Dr Pascal Birman
Scientific
Phaxiam Therapeutics