3-day Intravenous Antibiotic Treatment Versus 3-day Intravenous Followed by 7-day Oral Antibiotic Treatment for Acute Pyelonephritis in Children 1 Month to 3 Years Old: a Non-inferiority Open Randomized Multicentric Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 480
- 试验地点
- 14
- 主要终点
- Recurrence of febrile urinary tract infection
研究概览
简要总结
Antibiotic therapies currently recommended for the treatment of acute pyelonephritis (AP) in children, whether fully by the oral route or initially intravenous (IV, 3 days) followed by the oral route, have a duration of 7 to 14 days (10 days in France).
In children with no prior urological malformation, the global clinical and microbiological cure rate after antibiotic treatment completion is around 95%. Recurrence occurs in less than 5% of cases in the 3 months following AP. Renal scarring, when documented, concerns 15% of children 6 months after treatment. Renal scarring can be associated with chronic renal disease.
The investigators hypothesize that 3 days of IV treatment is equivalent to extending to 10 days with an oral to treat AP in children.
The investigators also hypothesize that while achieving equivalent clinical and prevention of re-infections in the following 3 months, 3 days of IV treatment reduces the risk of acquisition of resistant strains of Enterobacteriaceae and increases the gut microbotia diversity compared to extending to 10 days with an oral therapy.
详细描述
1.0 Hypothesis for the study
Antibiotic therapies currently recommended for the treatment of acute pyelonephritis (AP) in children, whether fully by the oral route or initially intravenous (IV, 3 days) followed by the oral route, have a duration of 7 to 14 days (10 days in France).
In children with no prior urological malformation, the global clinical and microbiological cure rate after antibiotic treatment completion is around 95%. Recurrence occurs in less than 5% of cases in the 3 months following AP. Renal scarring, when documented, concerns 15% of children 6 months after treatment. Renal scarring can be associated with chronic renal disease.
The investigators hypothesize that 3 days of IV treatment is equivalent to extending to 10 days with an oral therapy to prevent long-term renal scarring.
The investigators also hypothesize that while achieving equivalent clinical and microbiological success, and prevention of re-infections in the following 3 months, 3 days of IV treatment reduces the risk of acquisition of resistant strains of Enterobacteriaceae and increases the gut microbotia diversity compared to extending to 10 days with an oral 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
- None
入排标准
- 年龄范围
- 1 Month 至 3 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 1 month and < 3 years
- •For children younger than 3 months, gestational age > 34 WA
- •First episode of urinary tract infection
- •AP defined by temperature ≥ 38°C on day of diagnosis AND positive urinalysis (white cell counts ≥ 10^4/mL) with a positive urine culture with one Gram- negative bacillus ≥ 104 UFC/mL. The child temperature will have to be measured with a thermometer according to the French national recommendations [Health Insurance website (AMELI ;see: - https://www.ameli. fr/assure/sante/bons-gestes/soins/prendre-temperature); HAS (see: https://www.has-sante. fr/jcms/c_2674284/fr/prise-en-charge-de-la-fievre-chez-l-enfant)].
- •Initial treatment by either ceftriaxone AND/OR amikacin
- •Outpatient or hospitalised
- •Non-inclusion Criteria:
- •Urine collected by bag
- •Urine culture growing more than one dominant bacterium (cf section 6.2 of the protocol)
- •Catheter-associated acute pyelonephritis
- •Known congenital anomalies of the kidney and genitourinary tract (other than vesicoureteral reflux and pyelocaliceal dilatation < 10 mm)
- •Previous surgery of the genitourinary tract (except circumcision in male children)
- •Abnormal renal function for age and weight (defined by a serum creatinine >40µmol/L before 1 year and >75µmol between 1 year et 3 years)
- •Known immunocompromising condition (e.g., HIV, primary immunodeficiency, sickle cell disease, use of chronic corticosteroids or other immunosuppressive agents)
- •Antibiotic prophylaxis for any reason OR antibiotic treatment in the last 7 days (except treatment administered for the AP)
- •Known hypersensitivity to at least one of the active substances /excipients: ceftriaxone (including other cephalosporins and other beta-lactams) and amikacin (including other aminoglycosids).
- •Known hypersensitivity to at least one of the active substances /excipients: cotrimoxazole (=sulfamethoxazole/trimethoprim) (including other drugs containing sulfonamides) and cefixime (including other cephalosporins)
- •Known blood dyscrasias (megaloblastic haematopoiesis)
- •Known severe hepatic insufficiency
- •Known G6PD deficiency
- •No written consent from holders of parental authority
- •Non-affiliation to a social security system (as beneficiary or entitled person)
- •Children whose follow-up is not carried out in the centre
- •Participation in another interventional or minimal risk trial
- •Randomization criteria :
- •Three days of taking antibiotics (IV or IM) (no interruption or discontinuation)
- •Positive urine culture with Gram negative bacillus ≥ 10^4 UFC/mL
- •Favorable clinical outcome at day of randomization (D2 or D3) defined by temperature < 38°C at day of randomization and absence of fever measured > 38°C for at least 12 hours AND no abdominal pain AND no feeding problem AND investigator agreement
- •No renal abscess AND congenital anomalies of the kidney and genitourinary tract (other than vesicoureteral reflux and pyelocaliceal dilatation < 10 mm) on the renal ultrasound performed between D0 and day of randomization
- •No more than 1 type of dominant bacteria on the urine culture
- •Sensitivity to the initial antibiotic treatment
- •Sensitivity to cefixime OR cotrimoxazole
排除标准
- 未提供
研究组 & 干预措施
Experimental group: Discontinuation of treatment
For patients randomized in the experimental group, the patient receives 3-day IV therapy and the treatment is interrupted.
干预措施: IV Antibacterial Agents (Drug)
Experimental group: Discontinuation of treatment
For patients randomized in the experimental group, the patient receives 3-day IV therapy and the treatment is interrupted.
干预措施: Fecal/Rectal Swab (Procedure)
Experimental group: Discontinuation of treatment
For patients randomized in the experimental group, the patient receives 3-day IV therapy and the treatment is interrupted.
干预措施: PCT assay (Procedure)
Control group: Usual practice
For patients randomized in the control group, the treatment for acute pyelonephritis is based on the attending clinician's practice and according to the usual practice: 3-day IV therapy followed by a 7-day oral antibiotic therapy.
干预措施: IV Antibacterial Agents (Drug)
Control group: Usual practice
For patients randomized in the control group, the treatment for acute pyelonephritis is based on the attending clinician's practice and according to the usual practice: 3-day IV therapy followed by a 7-day oral antibiotic therapy.
干预措施: Orally antibacterial agents (Drug)
Control group: Usual practice
For patients randomized in the control group, the treatment for acute pyelonephritis is based on the attending clinician's practice and according to the usual practice: 3-day IV therapy followed by a 7-day oral antibiotic therapy.
干预措施: Fecal/Rectal Swab (Procedure)
Control group: Usual practice
For patients randomized in the control group, the treatment for acute pyelonephritis is based on the attending clinician's practice and according to the usual practice: 3-day IV therapy followed by a 7-day oral antibiotic therapy.
干预措施: PCT assay (Procedure)
结局指标
主要结局
Recurrence of febrile urinary tract infection
时间窗: 28 days (± 3 days) after the completion of antibiotic treatment.
Demonstrate the non-inferiority of a 3-day intravenous (IV) antibiotic therapy versus a 3-day IV therapy followed by a 7-day oral antibiotic therapy for the treatment of AP in children in term of the is recurrence of febrile urinary tract infection within a 28 -days period after the completion of antibiotic treatment respectively at D31 (+/- 3 days) for the experimental group and D38 (+/- 3 days) for the control group.. The recurrence will be defined as: fever ≥ 38°C associated with a positive urinalysis (white cell counts ≥ 10\^4/mL) with a positive urine culture with one Gram-negative bacillus ≥ 10\^4 UFC/mL
次要结局
- Clinical cure(D10 (+/- 3 days) for the experimental group and D17 (+/- 3 days) for the control group.)
- Colonization with antimicriobial-resistant Enterobacteriaceae(days of randomization and at D10 (+/- 3 days) for the experimental group and D17 (+/- 3 days) for the control group)
- Bacterial diversity of the intestinal microbiota(Inclusion, randomization and at D10 (+/- 3 days) and D31 (+/- 3 days) for the experimental group, and D17 (+/- 3 days) and D38 (+/- 3 days) for the control group.)
- Recurrence of AP(90 days after the beginning of therapy)