Randomized Phase II Study of Antibiotic Prophylaxis With Fosfomycin vs Amikacin in Transurethral Resection of Bladder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Incidence of urinary tract infection after transurethral resection of bladder
研究概览
简要总结
Antimicrobial prophylaxis in urological procedures is aimed to reduce the risk of local and systemic postoperative infections such as urinary tract infection or surgical site infection. It should be recommended only when the potential benefit exceeds the anticipated risks and costs. However, a wide variation in the use of periprocedural prophylactic antibiotics has been demonstrated, which frequently is incurred as an inappropriate selection of antimicrobials, inadequate schedule of administration or excessive duration of prophylaxis.
The increase in multidrug resistance of antibiotics in recent decades has been associated with its misuse, resulting in an increased rate of morbidity and mortality, prolonged hospital stays and increased care costs. Specifically, resistance to fluoroquinolones has increased its prevalence, a group of antibiotics widely used in urology. Therefore, local resistance patterns should be considered before following recommendations, especially in populations with poor control of antimicrobial use.
Transurethral resection of bladder (TURB) has become a frequent surgical procedure, as it is the main diagnostic and therapeutic tool for bladder cancer, representing the ninth most common malignancy in the world. However, no recent randomized clinical trial has investigated antimicrobial prophylaxis for TURB. It is well known that an expected complication of TURB is urinary tract infection (UTI), which is the most common healthcare related infection worldwide.
Under this premise, a randomized clinical trial is proposed to analyze the current panorama of UTI as a transcendent postoperative complication of TURB, under the context of the new emerging resistance parameters. The use of fosfomycin trometamol is proposed as a good potential option for urological procedures due to its high activity against multidrug-resistant gram-negative bacteria and its favorable pharmacokinetic parameters that guarantees wide tissue penetration and a high urinary concentration, in a single dose, the which will be compared with the control group with traditional prophylaxis (amikacin). The relative risk of UTI will be estimated, as well as the attributable risk of the main risk factors associated with this infection, allowing a better characterization of this population for adequate decision making regarding this clinical challenge.
详细描述
In 1931, Stern and McCarthy created the first practical cut-out resectoscope, allowing endoscopic diagnosis and treatment of bladder tumors for the first time in history. From now on, TURB has been the cornerstone of the management of bladder tumors. Histological evaluation is essential for the precise classification and staging of this cancer, as well as the therapeutic modality of choice for most patients with bladder cancer
Epidemiology Bladder cancer is the most common malignancy of the urinary tract, being the seventh most common cancer in men and number 17 in women. The worldwide incidence is 9 per 100,000 men and 2 per 100,000 women. More than 75,000 new cases of bladder cancer are diagnosed in the United States of America annually, making bladder cancer the ninth most common malignancy of the urinary tract. In addition, bladder cancer is responsible for 15,000 annual deaths in the United States of America, which makes it the thirteenth cause of death in general and the second most common cause of death among genitourinary tumors
In Latin America, bladder cancer has an incidence of 5.6 per 100,000 inhabitants. Mexico lacks reliable records of cancer epidemiology, however, in Mexico it corresponds to 14.4% of genitourinary cancers, ranking as the fourth most frequent. Mortality in men is 3 per 100,000 and in women 1 per 100,000 with very high geographical variation due to unequal access to health services. In a second level hospital in Mexico City were reported 861 cases of genitourinary cancer, bladder cancer was accounted for 13%.
Urinary tract infection as a postoperative complication In urology, the act of instrumentation is a potential contributor of infection risk.
Before finalizing the TURB, a urethral catheter is placed to irrigate and wash the bladder three times with 100 mL of saline. At the end of the procedure, the bladder is completely drained and the function of the catheter is guaranteed to assess a subsequent irrigation in the postoperative period, for complications that may occur, such as haematuria or urinary retention due to obstruction of a clot and / or irrigation of intravesical chemotherapy. In the absence of complications, the catheter can be removed after 24 hours.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Care Provider, Investigator)
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
- •Patients 18 years old of age
- •Patients with a programmed TURB
- •Absence of urinary tract infection (negative urine culture and no clinical manifestations for urinary tract infection)
排除标准
- •Patients with asymptomatic bacteriuria
- •Patients with positive urine culture before procedure
- •Patients with urinary catheterization
研究组 & 干预措施
Control group (Amikacin)
Patients in the control group will receive amikacin as prophylactic antibiotic. It will be administered intravenously 30 minutes before procedure. Patients with an estimated glomerular filtration rate (EGFR) greater or equal than 70 ml/min will receive 1 gram of Amikacin. Patients with an EGFR less than 70 ml/min will received a calculated dose following the next parameters.
Patients with EGFR between 69-40 ml/min should receive: the calculated GFR x 0.18 = mg/kg.
Patients with EGFR less than 40 ml/min should receive: the calculated GFR x 0.36 = mg/kg.
干预措施: Amikacin (Drug)
Intervention group (Fosfomycin)
Patients in the intervention group will receive Fosfomycin trometamol as prophylactic antibiotic. It will be administered orally in the night before procedure. Patients must be on fasting and will receive 3 grams.
干预措施: Fosfomycin Tromethamine 3G Sachet (Drug)
结局指标
主要结局
Incidence of urinary tract infection after transurethral resection of bladder
时间窗: 30 days after procedure
Measurement tool: Clinical manifestations of urinary tract infection plus positive urine culture. Measurement unit: Colony-forming unit (CFU) per milliliter (mL) depending on how the urine sample was took. A positive urine culture will be confirmed using the next parameters: For midstream urine a count greater or equal to 100,000 CFU/mL and for urine obtained from a urethral catheter a count a count greater or equal to 100 CFU/mL Clinical manifestations of urinary tract infection: Patient presenting 1 or more of the following signs or symptoms: fever, dysuria, frequency, hematuria, lumbar pain, costovertebral angle tenderness)
Incidence of asymptomatic bacteriuria after transurethral resection of bladder
时间窗: 30 days after procedure
Measurement tool: Positive urine culture and no clinical manifestation of urinary tract infection Measurement unit: Colony-forming unit (CFU) per milliliter (mL) depending on how the urine sample was took. A urine culture will be positive using the next parameters: For midstream urine a count greater or equal to 100,000 CFU/mL and for urine obtained from a urethral catheter a count a count greater or equal to 100 CFU/mL No clinical manifestations of urinary tract infection
Relative Risk of urinary tract infection after transurethral resection of bladder
时间窗: 30 days after procedure
Measurement tool: Clinical manifestations of urinary tract infection plus positive urine culture. Measurement unit: Colony-forming unit (CFU) per milliliter (mL) depending on how the urine sample was took. A positive urine culture will be confirmed using the next parameters: For midstream urine a count greater or equal to 100,000 CFU/mL and for urine obtained from a urethral catheter a count a count greater or equal to 100 CFU/mL Clinical manifestations of urinary tract infection: Patient presenting 1 or more of the following signs or symptoms: fever, dysuria, frequency, hematuria, lumbar pain, costovertebral angle tenderness)
Relative risk of asymptomatic bacteriuria after transurethral resection of bladder
时间窗: 30 days after procedure
Measurement tool: Positive urine culture and no clinical manifestation of urinary tract infection Measurement unit: Colony-forming unit (CFU) per milliliter (mL) depending on how the urine sample was took. A urine culture will be positive using the next parameters: For midstream urine a count greater or equal to 100,000 CFU/mL and for urine obtained from a urethral catheter a count a count greater or equal to 100 CFU/mL No clinical manifestations of urinary tract infection
次要结局
- % of patients with I on ASA classification(During procedure)
- % of patients with muscle invasive bladder cancer(30 days after procedure)
- % of patients with non-muscle invasive bladder cancer(30 days after procedure)
- Relative risk of patients with I on ASA classification(During procedure)
- Relative risk of patients presenting a single bladder tumor(During procedure)
- Relative risk of patients presenting 2 to 7 bladder tumors(During procedure)
- Relative risk of patients presenting more than 7 bladder tumors(During procedure)
- % of patients presenting more than 7 bladder tumors(During procedure)
- % of patients presenting a single bladder tumor(During procedure)
- % of patients presenting 2 to 7 bladder tumors(During procedure)
- Relative risk of bleeding during surgery(During procedure)
- Relative risk of patients with II on ASA classification(During procedure)
- % of patients with II on ASA classification(During procedure)
- Relative risk of muscle invasive bladder cancer(30 days after procedure)
- Relative risk of non-muscle invasive bladder cancer(30 days after procedure)
- Relative risk of chronic cystitis(30 days after procedure)
- Relative risk of patients with III on ASA classification(During procedure)
- % of patients with III on ASA classification(During procedure)
- Relative risk of patients with IV on ASA classification(During procedure)
- % of patients with IV on ASA classification(During procedure)
- Relative risk of patients with a urethral catheter removed 24 hours after procedure(1 day after procedure)
- % of patients with a urethral catheter removed 24 hours after procedure(1 day after procedure)
- % of patients with chronic cystitis(30 days after procedure)
- Relative risk of number of days of urethral catheter after procedure(30 days after procedure)
研究者
Ricardo Alonso Castillejos Molina
Urology Attending
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran