Urinary Tract InfectionsPhase 3NCT00161330
Oral vs Initial Intravenous Antibiotic Treatment of Urinary Tract Infections in Children: a RCT
A Phase 3 study testing oral amoxicilline/clavulanic acid and iv ceftriaxone in people with Urinary Tract Infections, run by University of Padova.
Trial summary
The main objectives of the study are 1. to compare the efficacy of oral vs initial iv antibiotic treatment in children with a first episode of UTI 2. to assess the diagnostic power of the various imaging technique (renal ultrasonogram, voiding cystourethrogram, and renal scanning with technetium-99m-labeled… Read more about this study
- Who is it for?
- Ages 2 months to 6 years
- Conditions the study is for
- Urinary Tract Infections
- What is being tested?
- oral amoxicilline/clavulanic acid and iv ceftriaxone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 440 participants
- Where
- No sites listed yet
- Study dates
- Jun 2000to Jul 2005
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- age between 2 months and 6 years,
- normal renal function
- first episode of upper UTI (fever, 2 consecutive positive urinalysis, later confirmed by 2 cultures and high blood inflammation indices)
Who cannot join
- documented previous urinary tract malformation (prenatal ultrasound)
- seriously compromised general conditions (such as sepsis or vomit)
- hypersensitivity to the antibiotics considered.
About this study
Official title: A Multicenter Randomized Controlled Trial of Antibiotic Treatment in Children With Urinary Tract Infections: Oral Amoxicillin/Clavulanic Acid vs Initial iv Ceftriaxone.
The main objectives of the study are
- to compare the efficacy of oral vs initial iv antibiotic treatment in children with a first episode of UTI
- to assess the diagnostic power of the various imaging technique (renal ultrasonogram, voiding cystourethrogram, and renal scanning with technetium-99m-labeled dimercaptosuccinic acid)
Read the detailed description
Background. Upper urinary tract infections (UTIs) are common in children, but attitudes toward the diagnosis and the acute treatment are heterogeneous among pediatricians and pediatric nephrologists. In effect the choice of antibiotic regimens is largely empirical and based on local practice, with no rationale for the choice of oral or parenteral administration. A retrospective study (1993-97) showed that in 1333 (36 % M) hospitalized children because of a prove UTI, parenteral antibiotic was given initially to 756 (57.2%) of the population studied.
We are aware of a unique randomized clinical trial, which has shown no differences in the short term (mean time to defervescence) and long term outcomes (symptomatic reinfections and renal scarring) of children receiving oral cefixime for 14 days versus vs initial iv cefotaxime for 3 days, followed by oral cefixime for 11 days.
The management of patients with UTI consists not only in antibiotic treatment of acute episodes, but also in the global evaluation of any risk factors. Current recommendations for imaging of the urinary tract are not based on prospective studies of outcomes (development of renal scars). A recent publication (Hoberman et al) suggests that renal ultrasonography and DMSA scanning at the time of acute illness are of limited value and recommends the routine use of voiding cystourethrography to identify children with reflux.
Aims.
Main objective of the study is:
- to compare the efficacy of oral vs initial iv antibiotic treatment in children with a first episode of UTI;
Secondary objectives of the study are:
- to assess the diagnostic power of the various imaging technique (renal ultrasonogram, voiding cystourethrogram, and renal scanning with technetium-99m-labeled dimercaptosuccinic acid);
- to evaluate a possible role of genetic polymorphisms implicated in the evolution of kidney damage
- to obtain area based protocols for the treatment and hospitalization of children with UTI.
Study design. A randomised, controlled, open-label, 2-armed, parallel-group study comparing the safety and efficacy of oral antibiotic (10 days of amoxicillin + clavulanic acid 50 mg/Kg/day), vs initial iv treatment (ceftriaxon 50 mg/Kg/day until defervescence) followed by oral treatment (amoxicillin + clavulanic acid) for a total of 10 days, in children with a first episode of UTI.
Criteria for the diagnosis of upper UTI upon entry
- Urinalysis (two concordant consecutive tests)
- Urine WBC ( higher 25/ul = 1+ with dipstick)
- Urine culture (two concordant consecutive tests)
- Growth of only one microorganism > 100,000 CFU
- Fever higher than 38°C (NB: in the first 6 months of life fever is not an essential criterion)
- Inflammation indices in the first 48 hours ESR higher than 30 and/or C-reactive Protein more than 3 times the upper limit of normal values
- Neutrophils higher than the normal values for age
The diagnosis of upper UTI is made by presence of criteria 1, 2 and at least two of the others.
Assuming that 15% of children with pyelonephritis and treated iv will develop renal scars at the 12 month DMSA, defining efficacy as an incidence of 10% per group and setting alfa error = 0.05 and power = 80%, 220 patients per group (i.e. a total of 440 patients) are required.
The computer generated randomization list is stratified for hospital, sex and age (< o > than 2 years) and based on variable blocks of 10 or more.
Primary end points are:1. Duration of fever (>38°), 2. Sterilization of the urine, 3. Reduction of the blood inflammatory indices, 4. Incidence of renal scarring documented at 12 month.
The imaging diagnostic work-up is as follow: sonography (US) of the kidney and the bladder and DMSA renal scintigraphy within 10 days from onset of antibiotic treatment and at the end of the study (12 months), voiding cystourethrography (VC) 1-2 months after UTI.
- Conditions
- Urinary Tract Infections
- Being tested
- oral amoxicilline/clavulanic acid, iv ceftriaxone
- Keywords
- urinary tract infection,, antibiotic treatment, childhood, amoxicilline/clavulanic acid, ceftriaxone, renal ultrasonography, renal scintigraphy
- Medical subject headings
- Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral amoxicilline/clavulanic acidDrug
iv ceftriaxoneDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
1. Duration of fever (>38°),
2. Sterilization of the urine,
3. Reduction of the blood inflammatory indices,
4. Incidence of renal scarring documented at 12 month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startJun 2000
- Study completionJul 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 440 participants
Sponsor and investigators
- Lead sponsor
- University of Padova
- Sponsor type
- University, hospital or other
- Collaborators
- Regione Veneto, IL Sogno di Stefano
- Investigators
- Graziella Zacchello, Professor, Study chair, Nephrology, dialysis and transplant unit, Pediatric Departement, Azienda ospdealiera-università, PadovaAntonella Toffolo, Dr, Principal investigator, Pediatric Unit, Ospedale di Oderzo, ItalyGiovanni Montini, Dr, Principal investigator, Nephrology, Dialysis and Transplant Unit, Pediatric Departement, Azienda Ospedaliera - Università, Padova Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00161330
- Sponsor's protocol ID
- IRIS 1
- Status last verified
- Jul 2004
- First submitted
- 8 Sep 2005
- Last updated
- 14 Dec 2020
- Results posted
- No
Publications
Ghiro L, Cracco AT, Sartor M, Comacchio S, Zacchello G, Dall'Amico R; Veneto Urinary Tract Infection Study Group. Retrospective study of children with acute pyelonephritis. Evaluation of bacterial etiology, antimicrobial susceptibility, drug management and imaging studies. Nephron. 2002 Jan;90(1):8-15. doi: 10.1159/000046308.
PubMed 11744799Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, Kearney DH, Reynolds EA, Ruley J, Janosky JE. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics. 1999 Jul;104(1 Pt 1):79-86. doi: 10.1542/peds.104.1.79.
PubMed 10390264Downs SM. Technical report: urinary tract infections in febrile infants and young children. The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement. Pediatrics. 1999 Apr;103(4):e54. doi: 10.1542/peds.103.4.e54.
PubMed 10103346Jakobsson B, Esbjorner E, Hansson S. Minimum incidence and diagnostic rate of first urinary tract infection. Pediatrics. 1999 Aug;104(2 Pt 1):222-6. doi: 10.1542/peds.104.2.222.
PubMed 10428998Cornu C, Cochat P, Collet JP, Delair S, Haugh MC, Rolland C. Survey of the attitudes to management of acute pyelonephritis in children. GEP. Pediatr Nephrol. 1994 Jun;8(3):275-7. doi: 10.1007/BF00866331.
PubMed 7917849Jodal U. Treatment trials on children with acute pyelonephritis. Pediatr Nephrol. 1994 Jun;8(3):278-9. doi: 10.1007/BF00866332. No abstract available.
PubMed 7917850Hoberman A, Charron M, Hickey RW, Baskin M, Kearney DH, Wald ER. Imaging studies after a first febrile urinary tract infection in young children. N Engl J Med. 2003 Jan 16;348(3):195-202. doi: 10.1056/NEJMoa021698.
PubMed 12529459Levtchenko EN, Ham HR, Levy J, Piepsz A. Attitude of Belgian pediatricians toward strategy in acute pyelonephritis. Pediatr Nephrol. 2001 Feb;16(2):113-5. doi: 10.1007/s004670000531.
PubMed 11261676Hewitt IK, Zucchetta P, Rigon L, Maschio F, Molinari PP, Tomasi L, Toffolo A, Pavanello L, Crivellaro C, Bellato S, Montini G. Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials. Pediatrics. 2008 Sep;122(3):486-90. doi: 10.1542/peds.2007-2894.
PubMed 18762516Montini G, Toffolo A, Zucchetta P, Dall'Amico R, Gobber D, Calderan A, Maschio F, Pavanello L, Molinari PP, Scorrano D, Zanchetta S, Cassar W, Brisotto P, Corsini A, Sartori S, Da Dalt L, Murer L, Zacchello G. Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial. BMJ. 2007 Aug 25;335(7616):386. doi: 10.1136/bmj.39244.692442.55. Epub 2007 Jul 4.
PubMed 17611232
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Controlled Trial of Antibiotic Treatment in Children With Urinary Tract Infections: Oral Amoxicillin/Clavulanic Acid vs Initial iv Ceftriaxone.
- ClinicalTrials.gov ID
- NCT00161330
- Acronym / sponsor ID
- IRIS 1
- Conditions
- Urinary Tract Infections
- Keywords
- urinary tract infection,, antibiotic treatment, childhood, amoxicilline/clavulanic acid, ceftriaxone, renal ultrasonography, renal scintigraphy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 440 participants
- Lead sponsor
- University of PadovaUniversity, hospital or other
- Collaborators
- Regione Veneto, IL Sogno di Stefano
- Study start
- Jun 2000
- Study completion
- Jul 2005
- First posted
- 12 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objectives of the study are
- to compare the efficacy of oral vs initial iv antibiotic treatment in children with a first episode of UTI
- to assess the diagnostic power of the various imaging technique (renal ultrasonogram, voiding cystourethrogram, and renal scanning with technetium-99m-labeled dimercaptosuccinic acid)
Detailed description
Background. Upper urinary tract infections (UTIs) are common in children, but attitudes toward the diagnosis and the acute treatment are heterogeneous among pediatricians and pediatric nephrologists. In effect the choice of antibiotic regimens is largely empirical and based on local practice, with no rationale for the choice of oral or parenteral administration. A retrospective study (1993-97) showed that in 1333 (36 % M) hospitalized children because of a prove UTI, parenteral antibiotic was given initially to 756 (57.2%) of the population studied.
We are aware of a unique randomized clinical trial, which has shown no differences in the short term (mean time to defervescence) and long term outcomes (symptomatic reinfections and renal scarring) of children receiving oral cefixime for 14 days versus vs initial iv cefotaxime for 3 days, followed by oral cefixime for 11 days.
The management of patients with UTI consists not only in antibiotic treatment of acute episodes, but also in the global evaluation of any risk factors. Current recommendations for imaging of the urinary tract are not based on prospective studies of outcomes (development of renal scars). A recent publication (Hoberman et al) suggests that renal ultrasonography and DMSA scanning at the time of acute illness are of limited value and recommends the routine use of voiding cystourethrography to identify children with reflux.
Aims.
Main objective of the study is:
- to compare the efficacy of oral vs initial iv antibiotic treatment in children with a first episode of UTI;
Secondary objectives of the study are:
- to assess the diagnostic power of the various imaging technique (renal ultrasonogram, voiding cystourethrogram, and renal scanning with technetium-99m-labeled dimercaptosuccinic acid);
- to evaluate a possible role of genetic polymorphisms implicated in the evolution of kidney damage
- to obtain area based protocols for the treatment and hospitalization of children with UTI.
Study design. A randomised, controlled, open-label, 2-armed, parallel-group study comparing the safety and efficacy of oral antibiotic (10 days of amoxicillin + clavulanic acid 50 mg/Kg/day), vs initial iv treatment (ceftriaxon 50 mg/Kg/day until defervescence) followed by oral treatment (amoxicillin + clavulanic acid) for a total of 10 days, in children with a first episode of UTI.
Criteria for the diagnosis of upper UTI upon entry
- Urinalysis (two concordant consecutive tests)
- Urine WBC ( higher 25/ul = 1+ with dipstick)
- Urine culture (two concordant consecutive tests)
- Growth of only one microorganism > 100,000 CFU
- Fever higher than 38°C (NB: in the first 6 months of life fever is not an essential criterion)
- Inflammation indices in the first 48 hours ESR higher than 30 and/or C-reactive Protein more than 3 times the upper limit of normal values
- Neutrophils higher than the normal values for age
The diagnosis of upper UTI is made by presence of criteria 1, 2 and at least two of the others.
Assuming that 15% of children with pyelonephritis and treated iv will develop renal scars at the 12 month DMSA, defining efficacy as an incidence of 10% per group and setting alfa error = 0.05 and power = 80%, 220 patients per group (i.e. a total of 440 patients) are required.
The computer generated randomization list is stratified for hospital, sex and age (< o > than 2 years) and based on variable blocks of 10 or more.
Primary end points are:1. Duration of fever (>38°), 2. Sterilization of the urine, 3. Reduction of the blood inflammatory indices, 4. Incidence of renal scarring documented at 12 month.
The imaging diagnostic work-up is as follow: sonography (US) of the kidney and the bladder and DMSA renal scintigraphy within 10 days from onset of antibiotic treatment and at the end of the study (12 months), voiding cystourethrography (VC) 1-2 months after UTI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 2 months to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- age between 2 months and 6 years,
- normal renal function
- first episode of upper UTI (fever, 2 consecutive positive urinalysis, later confirmed by 2 cultures and high blood inflammation indices)
Key exclusion criteria (3 listed)
- documented previous urinary tract malformation (prenatal ultrasound)
- seriously compromised general conditions (such as sepsis or vomit)
- hypersensitivity to the antibiotics considered.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oral amoxicilline/clavulanic acid | Drug | – |
| iv ceftriaxone | Drug | – |
Primary outcome
1. Duration of fever (>38°),
2. Sterilization of the urine,
3. Reduction of the blood inflammatory indices,
4. Incidence of renal scarring documented at 12 month.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2020.
- Background: PubMed 11744799Ghiro L, Cracco AT, Sartor M, Comacchio S, Zacchello G, Dall'Amico R; Veneto Urinary Tract Infection Study Group. Retrospective study of children with acute pyelonephritis. Evaluation of bacterial etiology, antimicrobial susceptibility, drug management and imaging studies. Nephron. 2002 Jan;90(1):8-15. doi: 10.1159/000046308.
- Background: PubMed 10390264Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, Kearney DH, Reynolds EA, Ruley J, Janosky JE. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics. 1999 Jul;104(1 Pt 1):79-86. doi: 10.1542/peds.104.1.79.
- Background: PubMed 10103346Downs SM. Technical report: urinary tract infections in febrile infants and young children. The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement. Pediatrics. 1999 Apr;103(4):e54. doi: 10.1542/peds.103.4.e54.
- Background: PubMed 10428998Jakobsson B, Esbjorner E, Hansson S. Minimum incidence and diagnostic rate of first urinary tract infection. Pediatrics. 1999 Aug;104(2 Pt 1):222-6. doi: 10.1542/peds.104.2.222.
- Background: PubMed 7917849Cornu C, Cochat P, Collet JP, Delair S, Haugh MC, Rolland C. Survey of the attitudes to management of acute pyelonephritis in children. GEP. Pediatr Nephrol. 1994 Jun;8(3):275-7. doi: 10.1007/BF00866331.
- Background: PubMed 7917850Jodal U. Treatment trials on children with acute pyelonephritis. Pediatr Nephrol. 1994 Jun;8(3):278-9. doi: 10.1007/BF00866332. No abstract available.
- Background: PubMed 12529459Hoberman A, Charron M, Hickey RW, Baskin M, Kearney DH, Wald ER. Imaging studies after a first febrile urinary tract infection in young children. N Engl J Med. 2003 Jan 16;348(3):195-202. doi: 10.1056/NEJMoa021698.
- Background: PubMed 11261676Levtchenko EN, Ham HR, Levy J, Piepsz A. Attitude of Belgian pediatricians toward strategy in acute pyelonephritis. Pediatr Nephrol. 2001 Feb;16(2):113-5. doi: 10.1007/s004670000531.
- Derived from this study: PubMed 18762516Hewitt IK, Zucchetta P, Rigon L, Maschio F, Molinari PP, Tomasi L, Toffolo A, Pavanello L, Crivellaro C, Bellato S, Montini G. Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials. Pediatrics. 2008 Sep;122(3):486-90. doi: 10.1542/peds.2007-2894.
- Derived from this study: PubMed 17611232Montini G, Toffolo A, Zucchetta P, Dall'Amico R, Gobber D, Calderan A, Maschio F, Pavanello L, Molinari PP, Scorrano D, Zanchetta S, Cassar W, Brisotto P, Corsini A, Sartori S, Da Dalt L, Murer L, Zacchello G. Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial. BMJ. 2007 Aug 25;335(7616):386. doi: 10.1136/bmj.39244.692442.55. Epub 2007 Jul 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Graziella Zacchello, Professor study chair
Nephrology, dialysis and transplant unit, Pediatric Departement, Azienda ospdealiera-università, Padova
Antonella Toffolo, Dr principal investigator
Pediatric Unit, Ospedale di Oderzo, Italy
Giovanni Montini, Dr principal investigator
Nephrology, Dialysis and Transplant Unit, Pediatric Departement, Azienda Ospedaliera - Università, Padova Italy
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing oral amoxicilline/clavulanic acid and iv ceftriaxone in people with Urinary Tract Infections, run by University of Padova.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1. Duration of fever (>38°),. The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00161330, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2020.