Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in Febrile UTIs Caused by ESBL-producing Enterobacterales (PACUTI)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 330
- 试验地点
- 5
- 主要终点
- Clinical cure
研究概览
简要总结
To evaluate if the combination of pivmecillinam and clavulanic acid (PAC) is non-inferior to ciprofloxacin, trimethoprim-sulfamethoxazole or ertapenem as step down oral therapy in patients with febrile UTI caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales (EPE).
详细描述
A recent observational cohort study supports the notion that beta-lactams can be used with similar efficacy to fluoroquinolones as step down therapy in bacteremic E. coli UTI's. As such, pivmecillinam clavulanic acid (PAC) constitute an appealing per oral alternative, but the combination's safety and efficacy has not been evaluated in a clinical trial The aim of this trial is to investigate whether the PAC combination is non-inferior to ciprofloxacin, trimethoprim-sulfamethoxazole or ertapenem as step down oral therapy in treating EPE-causing febrile UTI.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Fever (≥ 38.3 C) or shaking chills at least once at home or in hospital
- •Clinical suspicion of UTI including at least one of the following symptoms:
- •Dysuria, urinary urgency, difficulty urinating, new or worsened urinary incontinence, macroscopic haematuria or increased urinary frequency
- •Low abdominal pain or flank pain with percussion or palpation tenderness over kidneys and/or bladder.
- •Urine (≥ 103 CFU/mL) and/or blood culture positive for EPE* with susceptibility to pivmecillinam†.
- •In-patient who has received 1-5 days of EPE-active‡ intravenous antibiotics
- •Discontinuing parenteral treatment and starting treatment with oral antibiotics is considered safe according to the treating physician.
- •EPE refers to ESBL-producing Enterobacterales. This includes Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, and Citrobacter koseri.
- •Susceptibility for pivmecillinam in the study is based on zone diameter breakpoints for pyelonephritis (≥ 20 mm) which was received by personal communication with professor Christian Giske, the chairman of the European Committee of Antimicrobial Susceptibility Testing (EUCAST) (26).
- •EPE-active intravenous antibiotics refers to EUCAST susceptibility testing and will most often be piperacillin-tazobactam, meropenem or imipenem-cilastatin in the Swedish setting, and less often aminoglycosides or newer beta-lactamase-inhibitor-containing beta-lactam antibiotics (27). Participants who have only received one dose of EPE-active intravenous antibiotics are also eligible and are considered within the "1-5 days" of antibiotics.
- •Patients may only be recruited and randomised once in this trial.
- •Exclusion criteria (any of the following)
- •Known or suspected pregnancy.
- •Known or suspected life-threatening allergy towards beta-lactam antibiotics.
- •Clinical isolate of EPE is resistant to ciprofloxacin, TMX and ertapenem.
- •Severe renal insufficiency with estimated glomerular filtration rate (eGFR) <10mL/min or requiring any form of dialysis.
- •Severe decompensated liver failure (i.e., child Pugh class B or C).
- •Genetic metabolic diseases associated with severe carnitine deficiency.
- •Megaloblastic haematopoiesis.
- •Co-treatment with valproate or valproic acid (due to interaction with pivmecillinam and ertapenem respectively)
- •Other reason to which patient is unfit to be included in the study according to treating physician, e.g., cognitive impairment preventing informed consent and follow-up, inability to speak and/or read Swedish, missing national personal identification number or missing telephone number preventing follow-up or planned duration of antibiotics > 10 days due to complicating factors.
排除标准
- 未提供
研究组 & 干预措施
PAC treatment
干预措施: Pivmecillinam and amoxicillin/clavulanic acid (Drug)
Standard treatment
干预措施: Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility (Drug)
结局指标
主要结局
Clinical cure
时间窗: Clinical cure 10 days (+/- 2 days)
Clinical cure defined as being alive with absence of fever (≥ 38.3 C) and resolution of, or return to non-infected baseline of, urinary tract symptoms (as defined in inclusion criteria) without additional antibiotic treatment (for UTI symptoms) based on fever control and a semi-structured interview at a live return visit to an independent physician (i.e. not previously involved in the care of the study participant) at an infectious disease clinic.
次要结局
- To compare the incidence of additional antibiotic subscriptions (for UTI) within 28 days between groups.(28 days)
- To compare the recurrence prevalence of EPE (phenotypically same species) in urine cultures 10 +/- 2 days after antibiotic treatment between groups (i.e., microbiological cure).(Up to 28 days)
- To compare participants' perception of treatment tolerability(10 days)
- To compare the incidence of early study drug discontinuation between groups.(10 days)
- To compare the all-cause mortality within 28 days between groups.(28 days)
- To compare re-admission to hospital (due to UTI-related symptoms) within 28 days between groups.(28 days)
- To compare the prevalence of EPE or carbapenemase-producing bacteria in faecal cultures 10 +/- 2 days after antibiotic treatment between groups.(Up to 28 days)
- To compare the incidence of drug-related serious adverse events (SAE) within 28 days between groups.(28 days)