E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute pyelonephritis in children 1 month to 3 years old |
Pyelonephrite chez des enfants agés de 1 mois a 3 ans. |
|
E.1.1.1 | Medical condition in easily understood language |
Pyelonephrite chez des enfants agés de 1 mois a 3 ans. |
Pyelonephrite chez des enfants agés de 1 mois a 3 ans. |
|
E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective is to 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 on the occurrence of renal scarring.
|
The main objective is to 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 on the occurrence of renal scarring.
The primary endpoint is the occurrence of renal scaring, as measured by cortical defect by dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy at 6 months after the beginning of therapy (day 180 ± 15 days).
|
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives and endpoints Secondary objectives: - To demonstrate the non-inferiority of a 3-day IV antibiotic treatment versus a 3-day IV followed by 7-day oral antibiotic treatment for AP in children 1 month to 3 years old in terms of: 1. Clinical cure at day 14 2. Recurrence of AP within the 90 days after the beginning of therapy. - To compare between the two treatment arms: 3. The rate of colonization with antimicrobial-resistant Enterobacteriaceae 4. The bacterial diversity of the intestinal microbiota. .
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 1 month ≤ Age < 3 years - For children younger than 3 months, gestational age > 34 WGA - First episode of urinary tract infection. - AP defined by temperature ≥ 38°C on day of diagnosis AND positive urinalysis (white cell counts ≥ 104/mL) AND Gram-negative rods in Gram-stained urine - Initial treatment by either ceftriaxone AND/OR amikacin. - Outpatient or hospitalised
|
- 1 month ≤ Age < 3 years - For children younger than 3 months, gestational age > 34 WGA - First episode of urinary tract infection. - AP defined by temperature ≥ 38°C on day of diagnosis AND positive urinalysis (white cell counts ≥ 104/mL) AND Gram-negative rods in Gram-stained urine - Initial treatment by either ceftriaxone AND/OR amikacin. - Outpatient or hospitalised
|
|
E.4 | Principal exclusion criteria |
- Urine collected by bag. - Urine culture growing more than one bacteria. - Catheter-associated AP. - 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 - Immunocompromising condition (e.g., HIV, primary immunodeficiency, sickle cell disease, use of chronic corticosteroids or other immunosuppressive agents). - A history of AP or other urinary tract infection. - Antibiotic prophylaxis for any reason OR antibiotic treatment in the last 7 days. - Known hypersensitivity to at least one of the active substances /excipients: ceftriaxone (include cephalosporin et beta-lactams)and amikacin (include aminoside)Known hypersensitivity to at least one of the active substances /excipients: cotrimoxazole (=sulfamethoxazole/trimethoprim) (include sulfonamide) and cefixime (include cephalosporin) - Known hypersensitivity to 99mTc-DMSA (medicinal product used for renal scintigraphy) - Severe hepatic insufficiency (transaminases ≥ 3N) - Known G6PD deficiency - No written consent from holders of parental authority, or refusal of the child to participate - Non-affiliation of the child in a social security (as beneficiary or entitled person) - Children whose follow-up is not carried out in the centre - Participation in another interventional or minimal risk trial
|
- Urine collected by bag. - Urine culture growing more than one bacteria. - Catheter-associated AP. - 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 - Immunocompromising condition (e.g., HIV, primary immunodeficiency, sickle cell disease, use of chronic corticosteroids or other immunosuppressive agents). - A history of AP or other urinary tract infection. - Antibiotic prophylaxis for any reason OR antibiotic treatment in the last 7 days. - Known hypersensitivity to at least one of the active substances /excipients: ceftriaxone (include cephalosporin et beta-lactams)and amikacin (include aminoside)Known hypersensitivity to at least one of the active substances /excipients: cotrimoxazole (=sulfamethoxazole/trimethoprim) (include sulfonamide) and cefixime (include cephalosporin) - Known hypersensitivity to 99mTc-DMSA (medicinal product used for renal scintigraphy) - Severe hepatic insufficiency (transaminases ≥ 3N) - Known G6PD deficiency - No written consent from holders of parental authority, or refusal of the child to participate - Non-affiliation of the child in a social security (as beneficiary or entitled person) - Children whose follow-up is not carried out in the centre - Participation in another interventional or minimal risk trial
|
|
E.5 End points |
E.5.1 | Primary end point(s) | |
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint is the occurrence of renal scaring, as measured by cortical defect by dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy at 6 months after the beginning of therapy (day 180 ± 15 days). |
The primary endpoint is the occurrence of renal scaring, as measured by cortical defect by dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy at 6 months after the beginning of therapy (day 180 ± 15 days). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints: - Clinical cure at the end of the antibiotic treatment (day 14 ± 3 days), defined by apyrexia AND no abdominal pain AND no feeding problem: medical visit. - Recurrent infection (including AP relapse or reinfection) within 90 days after the beginning of therapy (day 90 ± 15 days): phone call - Colonization with antimicrobial resistant Enterobacteriaceae in the gastrointestinal tract between at days 3 and 14. - Alpha-diversity measured by Shannon’s index at days 3, 14 and 45 |
- Secondary endpoints: - Clinical cure at the end of the antibiotic treatment (day 14 ± 3 days), defined by apyrexia AND no abdominal pain AND no feeding problem: medical visit. - Recurrent infection (including AP relapse or reinfection) within 90 days after the beginning of therapy (day 90 ± 15 days): phone call - Colonization with antimicrobial resistant Enterobacteriaceae in the gastrointestinal tract between at days 3 and 14. - Alpha-diversity measured by Shannon’s index at days 3, 14 and 45 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Pas de comparateur. Une continuation d'antibiotique versus arrêt antibiotique |
Nothing |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |