Clinical Trial Results:
Oral steroids for reducing renal scarring in infants with febrile urinary tract infections at high risk for renal scar development: a randomized controlled trial
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Summary
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EudraCT number |
2013-000388-10 |
Trial protocol |
IT |
Global end of trial date |
31 Dec 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Sep 2022
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First version publication date |
28 Sep 2022
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Other versions |
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Summary report(s) |
article 2021 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RF-2010-2318192
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AZIENDA ULSS N.9 - TREVISO, UOC PEDIATRIA
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Sponsor organisation address |
Piazzale Ospedale 1, 31100 Treviso, Treviso, Italy,
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Public contact |
PROF.SSA LIVIANA DA DALT, AZIENDA ULSS N.9 - TREVISO, UOC PEDIATRIA, 0039 0422322263, liviana.dadalt@unipd.it
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Scientific contact |
PROF.SSA LIVIANA DA DALT, AZIENDA ULSS N.9 - TREVISO, UOC PEDIATRIA, 0039 0422322263, liviana.dadalt@unipd.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Dec 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Dec 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Dec 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine the usefulness of steroid therapy (adjunctive to standard antibiotic treatment) in reducing renal scar development in infants with first febrile UTI, at higher risk based on PCT values ≥ 1 ng/mL, measured at the time of initial evaluation
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jun 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 48
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Worldwide total number of subjects |
48
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EEA total number of subjects |
48
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
48
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
total 437 assessed, 225 either did not meet inclusion criteria or met exclusion criteria. 131 did not complete study procedures, namely determination of serum PCT and/or urine collection through catheterization, 12 could not be approached by research staff and 21 declined consent; thus 48 patients underwent randomized and 18 completed follow-up | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Inclusion = age 2-24 months, fever > 37,5°C, positive disptick (> = 1 leucocyte esterase and/or nitrites) on urine sample collected by catheterization. Esclusion: immunodeficit, antobiotics in 48 h before evaluation, known kidney disease, prematurity, controindication to steroid therapy, recurrence or previuos urinary tract infection | |||||||||||||||||||||
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Period 1
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Period 1 title |
june 2014-dicember 2017 (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
Blinding implementation details |
two nuclear medicine physicians blinded to study allocation
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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dexamethasone + | |||||||||||||||||||||
Arm description |
dexamethasone plus routine therapy (antibiotic for 10 days) | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
dexamethasone +
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution in bottle
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Routes of administration |
Oral use
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Dosage and administration details |
0,15mg/kg per dose every 12 h for 4 days
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Arm title
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dexamethasone - | |||||||||||||||||||||
Arm description |
Routine therapy for febrile urinary tract infection (antibiotic for 10 days) | |||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
dexamethasone +
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Reporting group description |
dexamethasone plus routine therapy (antibiotic for 10 days) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
dexamethasone -
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Reporting group description |
Routine therapy for febrile urinary tract infection (antibiotic for 10 days) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Dexamethasone +
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The original sample size calculation on the hypothesis that dexamethasone would determine a renal scar reduction from 40% to 20%. Estimating a 10% rate of patients who did not fulfil the criteria for urinary tract infections diagnosis and 20% of lost to follow-up, a final number of 92 patients per group were required based on Freedman formula. Unanticipated difficult recruitment of patient in the study and their relevant loss to follow up prevented the completion of the study as originally designed. An interim assessment showed that based on the on the recruitment and attrition data, the completion of the study as initially planned was not feasible based on the available resources. We, therefore, used a Bayesian analysis to estimate the probability of treatment effect, given the limited number of patients we could enroll in the study based on the projection for patient enrolment and follow up estimated at the interim assessment.
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Subject analysis set title |
Dexamethasone -
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The original sample size calculation on the hypothesis that dexamethasone would determine a renal scar reduction from 40% to 20%. Estimating a 10% rate of patients who did not fulfil the criteria for urinary tract infections diagnosis and 20% of lost to follow-up, a final number of 92 patients per group were required based on Freedman formula. Unanticipated difficult recruitment of patient in the study and their relevant loss to follow up prevented the completion of the study as originally designed. An interim assessment showed that based on the on the recruitment and attrition data, the completion of the study as initially planned was not feasible based on the available resources. We, therefore, used a Bayesian analysis to estimate the probability of treatment effect, given the limited number of patients we could enroll in the study based on the projection for patient enrolment and follow
up estimated at the interim assessment.
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End points reporting groups
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Reporting group title |
dexamethasone +
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Reporting group description |
dexamethasone plus routine therapy (antibiotic for 10 days) | ||
Reporting group title |
dexamethasone -
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Reporting group description |
Routine therapy for febrile urinary tract infection (antibiotic for 10 days) | ||
Subject analysis set title |
Dexamethasone +
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The original sample size calculation on the hypothesis that dexamethasone would determine a renal scar reduction from 40% to 20%. Estimating a 10% rate of patients who did not fulfil the criteria for urinary tract infections diagnosis and 20% of lost to follow-up, a final number of 92 patients per group were required based on Freedman formula. Unanticipated difficult recruitment of patient in the study and their relevant loss to follow up prevented the completion of the study as originally designed. An interim assessment showed that based on the on the recruitment and attrition data, the completion of the study as initially planned was not feasible based on the available resources. We, therefore, used a Bayesian analysis to estimate the probability of treatment effect, given the limited number of patients we could enroll in the study based on the projection for patient enrolment and follow up estimated at the interim assessment.
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Subject analysis set title |
Dexamethasone -
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The original sample size calculation on the hypothesis that dexamethasone would determine a renal scar reduction from 40% to 20%. Estimating a 10% rate of patients who did not fulfil the criteria for urinary tract infections diagnosis and 20% of lost to follow-up, a final number of 92 patients per group were required based on Freedman formula. Unanticipated difficult recruitment of patient in the study and their relevant loss to follow up prevented the completion of the study as originally designed. An interim assessment showed that based on the on the recruitment and attrition data, the completion of the study as initially planned was not feasible based on the available resources. We, therefore, used a Bayesian analysis to estimate the probability of treatment effect, given the limited number of patients we could enroll in the study based on the projection for patient enrolment and follow
up estimated at the interim assessment.
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End point title |
Primary outcome | ||||||||||||||||||||
End point description |
Presence of renal scars on the Technetium 99m dimercaptosuccinic acid (DMSA) scan performed at the 6 months follow up. Outcome assessors were two nuclear medicine physicians, blinded to study allocation and unaware of patients clinical data, who interpreted the scans independently. Discrepancies were resolved by consensus if necessary.
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End point type |
Primary
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End point timeframe |
Follow up 6 months
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Attachments |
Untitled (Filename: Figure Patient selection Rescue trial.pdf) |
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| Notes [1] - Given the limited number, we were unable to assess the frequency of renal scarring in the subgroup [2] - Given the limited number, we were unable to assess the frequency of renal scarring in the subgroup [3] - Given the limited number, we were unable to assess the frequency of renal scarring in the subgroup [4] - Given the limited number, we were unable to assess the frequency of renal scarring in the subgroup |
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Statistical analysis title |
bayesian analysis | ||||||||||||||||||||
Statistical analysis description |
Bayesian analysis was used to estimate the probability of treatment effect, given the limited number of patients. In this analyses, the probability of treatment effect (posterior probability) is estimated considering the trial data and incorporating the prior probability distribution. The prior distribution includes treatment effect information provided by previous studies (clinical trial or pilot trials).
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Comparison groups |
dexamethasone - v dexamethasone +
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Number of subjects included in analysis |
18
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Analysis specification |
Post-hoc
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Analysis type |
other [5] | ||||||||||||||||||||
Method |
bayesian analysis | ||||||||||||||||||||
Parameter type |
bayesian analysis | ||||||||||||||||||||
Point estimate |
0.2
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Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.06 | ||||||||||||||||||||
upper limit |
0.29 | ||||||||||||||||||||
| Notes [5] - A sample size calculation was carried out for the Bayesian analysis, based on a Beta Binomial model for a difference in proportion outcome as suggested in the literature.We assumed an interval coverage of 0.9 with a length of 0.35. A Beta prior was considered for the computation based on previously published data on the proportion of renal scarring in both treatment and control groups. The achieved sample size consisted of 9 patients per group, for a total of 18 patients. |
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End point title |
Secondary outcomes | ||||||||||||||||||||
End point description |
Secondary outcomes were the presence of renal scarring in the subgroup of children with higher PCT values; the acceptability of adjunctive steroids treatment, in terms of the rate of discontinuation of treatment and the reported side effects.
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End point type |
Secondary
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End point timeframe |
Follow up 6 months
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Attachments |
Untitled (Filename: Figure Patient selection Rescue trial.pdf) |
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| Notes [6] - Given the limited number of recruited patients, we were unable to assess the frequency of renal scar [7] - Given the limited number of recruited patients, we were unable to assess the frequency of renal scar [8] - Given the limited number of recruited patients, we were unable to assess the frequency of renal scar [9] - Given the limited number of recruited patients, we were unable to assess the frequency of renal scar |
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| No statistical analyses for this end point | |||||||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
From started therapy with dexamethasone until 10-15 days after diagnosis of urinary tract infection
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Adverse event reporting additional description |
Only 1 child present transient behavioural change.
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
20.1
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| Frequency threshold for reporting non-serious adverse events: 0.05% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Only one patient of dexamethasone + group presented irritability during the treatment. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 May 2014 |
Modification of urine sample collection method for urine culture: previous study protocol described two different urine sample collection (catheterization or clean catch void). In this version of study protocol the urine sample method is only with catheterization to avoid methodology bias. |
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17 Jun 2015 |
Increase of partecipating centres because difficult recruitment of patients in the clinical study. |
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30 May 2017 |
1. Change of Principal study coordinator (from Prof. Liviana Da Dalt to DR. Floriana Scozzola)
2. Modification of clinical study partecipating centres (without Vicenza)
3. Change of name of clinical study sponosr (from AULSS9 to AULSS2)
4. Modification of the statistical analysis: use of a Bayesian analysis model |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Unanticipated difficult recruitment of patients in the study and their relevant loss to follow up prevented the completion of the study as originally designed. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/34032923 |
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