Piperacillin/Tazobactam Versus Carbapenems in Non-bacteremic Urinary Tract Infections Due to Extended-spectrum Β-lactamase (ESBL)-producing Escherichia Coli or Klebsiella Pneumoniae - (CAPITIS Study)
试验速览
- 阶段
- 4 期
- 状态
- 暂停
- 入组人数
- 198
- 试验地点
- 1
- 主要终点
- Clinical cure.
研究概览
简要总结
This study evaluates the efficacy in achieving clinical cure in non-bacteremic urinary tract infections (UTI) caused by Escherichia coli or Klebsiella pneumoniae producers of extended-spectrum β-lactamases (ESBL) in adult patients. Half of participants will receive Piperacillin/Tazobactam as treatment, while the other half will receive Carbapenems.
The investigators will verify that Piperacillin/Tazobactam is not inferior in achieving clinical cure, and that is not associated with a higher risk of adverse events in the directed treatment of non-bacteremic UTI compared to Carbapenems.
The researchers hope to improve the use of antibiotics in the non-bacteremic UTI, reducing the "collateral damage" related to a deterioration in the prognosis of patients and the generation of resistant germs caused by the use of broad-spectrum antibiotics as carbapenems.
详细描述
Urinary tract infection (UTI) is a common cause of hospitalization worldwide, the prevalence throughout the life of UTI has been reported in about 50,000 cases per 100,000 women and 13,000 per 100,000 men in the United States. Hospitalization for community-acquired UTI is about 33%. Furthermore, the UTI related to bladder catheterization during hospitalization is the most common type of infection acquired, representing 40% of all nosocomial infections. UTI hospitalization is associated with a high cost to the healthcare system.
The diagnosis of UTI is based on demonstrating the presence of bacteria urine in patients with suggestive clinical manifestations and verifying the host's inflammatory response to infection. The most common etiological agents include Escherichia coli, Klebsiella spp, and Proteus spp, with different prevalence and antibiotic susceptibility profiles among different populations.
Currently the appropriate treatment of UTI is a growing concern in the medical community because Gram-negative, specifically Enterobacteriaceae, bacteria have acquired genes encoding antibiotic resistance mechanisms. The β-lactamase spread spectrum (ESBL) are documented with increasing frequency among microorganisms causing UTI. Current treatment options for ESBL bacteria include nitrofurantoin, fosfomycin, piperacillin-tazobactam, carbapenems, and aminoglycosides.
Carbapenems and piperacillin-tazobactam are antibiotics used in medical practice for many years, both therapies are licensed for the treatment of non-bacteremic UTI; however, so far there is not enough evidence to discriminate the best choice for the treatment of non-bacteremic UTI (although carbapenems are considered drugs of choice for infections caused by these microorganisms), but carbapenems use has been associated with an increased risk of "collateral damage" related to the generation of resistant germs.
The investigators will compare between piperacillin/tazobactam and carbapenems the effectiveness in achieving clinical cure for non-bacteremic UTI caused by ESBL microorganisms. Researchers principal hypothesis is that Piperacillin/tazobactam is not inferior to carbapenems in achieving clinical cure in the targeted treatment of UTI caused by non-bacteremic due to E. coli or K. pneumoniae ESBL in adults requiring hospitalization. Researchers will verify too if Piperacillin/Tazobactam is not associated with increased risk of adverse events during the targeted treatment of non-bacteremic ITU caused by E. coli or K. pneumoniae ESBL in adults requiring hospital admission, compared with Carbapenems therapy.
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)
盲法说明
An investigator of the research project conducted daily monitoring of the patient and will not be involved in clinical decisions. The statistical analyzes performed finally be blind to the treatment received by the patients (carbapenems vs piperacillin/tazobactam).
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
- •Adults (≥18 years) with hospital admission for non-bacteremic UTI caused by E. coli or K. pneumoniae ESBL susceptible to piperacillin/tazobactam and carbapenems.
- •Presence of any risk factor associated with UTI due to ESBL germs: older age 64 years, diabetes mellitus, bladder catheter, previous antibiotics in the last 6 months, hospitalization in the last 6 months, urological surgery in the last 30 days, infections recurrent urinary.
- •Diagnosis of UTI confirmed by: 1) fever, 2) urine culture> 100000 CFU with isolation E. coli or K. pneumoniae ESBL susceptible to piperacillin / tazobactam and carbapenems, and 3) lumbar and / or abdominal pain with or without low urinary symptoms (dysuria, tenesmus, urgency), and 4) no other cause that explains the patient's symptoms
- •Signed informed consent.
- •Negative pregnancy test in fertile women.
排除标准
- •Non-acceptance of participation in the study.
- •Pregnancy.
- •Hypersensitivity and/or previous intolerance to penicillins, piperacillin/tazobactam or carbapenems.
- •Bacteremia, hematogenous infection or other concomitant infection.
- •Immunosuppression.
- •In case of obstructive uropathy, lack of early surgical resolution.
- •Evidence of acute or chronic prostatitis.
- •Renal abscess
- •Polycystic disease in the kidneys.
- •Palliative care or life expectancy <90 days.
- •Heart failure (NYHA) functional class III or IV.
- •Liver cirrhosis.
- •Renal insufficiency in dialysis treatment.
- •Empirical active treatment against bacteria isolated by urine cultures other than E. coli or K. pneumoniae BLEE.
- •Participation in another clinical trial for infections.
- •Hypersensitivity to amide-type local anesthetics.
研究组 & 干预措施
Carbapenems group
Meropenem (1g intravenously every 8 hours or adjusted to renal function) or Ertapenem (1g intravenously every 24 hours or adjusted to renal function) by 10 days.
干预措施: Meropenem (Drug)
Carbapenems group
Meropenem (1g intravenously every 8 hours or adjusted to renal function) or Ertapenem (1g intravenously every 24 hours or adjusted to renal function) by 10 days.
干预措施: Ertapenem 1000 MG (Drug)
Piperacillin/tazobactam.
Piperacillin / Tazobactam (4.5gr intravenously every 6 hours or adjusted to renal function) by 10 days.
干预措施: Piperacillin, Tazobactam 4-0.5G Solution for Injection (Drug)
结局指标
主要结局
Clinical cure.
时间窗: At 5-7 day after the end of treatment (cure test), or for early response after 5 days from the start of treatment.
Complete resolution of non-bacteremic urinary tract infection signs or symptoms (dysuria, urinary frequency, urinary urgency, suprapubic pain or temperature greater than 38 degrees Celsius) present at trial entry (and no new signs or symptoms) until the duration of investigational antibacterial drug therapy. Investigators will compare the rate of clinical cure between the two treatment lines.
次要结局
- Microbiologic cure.(At the 5-7 day after the end of treatment (cure test).)
- Adverse events in patient follow-up.(Daily until day 30 after the first day of administration of the study drugs.)
- Clinical or microbiological failure of antibiotic therapy in patient follow-up.(Daily until day 30 after the first day of administration of the study drugs.)
- Mortality in patient follow-up.(Until day 30 after the first day of administration of the study drugs.)
- Length of hospital stay in patient follow-up.(Until day 30 after the first day of administration of the study drugs.)
- ICU admission in patient follow-up.(Daily until day 30 after the first day of administration of the study drugs.)
- Relapse.(Daily until day 30 after the first day of administration of the study drugs.)
- Reinfection.(Daily until day 30 after the first day of administration of the study drugs.)
- Resistant clinical isolates in patient follow-up.(Daily until day 30 after the first day of administration of the study drugs.)