Primary: To determine whether three months of prophylactic treatment with co-trimoxazole causes a reduction in the number of days a child experiences at least two RTI symptoms in children aged 6 months to
ID
Source
Brief title
Condition
- Infections - pathogen unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine whether antibiotic prophylaxis is more effective than placebo in
the prevention of respiratory symptoms in children with recurrent RTIs at a
group-level. The difference in days with at least 2 RTI symptoms will be
calculated from baseline to 3 months after inclusion.
Secondary outcome
1. To determine whether co-trimoxazole prophylactic therapy reduces:
- Time to resolution of symptoms;
- The severity of symptoms defined by the number and type of different
infectious symptoms;
- Use of analgesics / antipyretics;
- Use of antibiotic treatment courses;
- Absenteeism from day care or school and/or parental absenteeism from work;
- Alterations in nutritional status.
2. To examine predictors (e.g. demographic, environmental, family history,
mucosal, microbiological and immunological characteristics) for the (absence
of) prophylactic treatment effect*
3. To examine whether cessation of antibiotic prophylactic treatment affects
the presence of RTI symptoms and how this correlates with clinical,
microbiological and immunological characteristics of the patients.
4. To record and evaluate adverse events.
5. To detect changes in microbial composition, shifts in AMR genes and
immunological changes in the group that received antibiotic prophylaxis
compared to the placebo group.
Background summary
Recurrent respiratory tract infections (RTIs) affect 15-20% of children aged
0-5 years and cause high disease burden, frequent doctor visits and are one of
the main reasons for hospital admission in childhood. Despite the common use of
co-trimoxazole as a prophylactic agent in children with recurrent RTIs, there
are no evidence-based guidelines for its use except for children suffering from
exclusively otitis media. More evidence of the effect of co-trimoxazole
prophylaxis on both clinical symptoms as well as microbiome deviation and
antibiotic resistance is needed.
Study objective
Primary: To determine whether three months of prophylactic treatment with
co-trimoxazole causes a reduction in the number of days a child experiences at
least two RTI symptoms in children aged 6 months to <=10 years with recurrent
RTIs, when compared to placebo.
Secondary:
1. To determine whether co-trimoxazole prophylactic therapy reduces:
- Time to resolution of symptoms;
- The severity of symptoms defined by the number and type of different
infectious symptoms;
- Use of analgesics / antipyretics;
- Use of antibiotic treatment courses;
- Absenteeism from day care or school and/or parental absenteeism from work;
- Alterations in nutritional status.
2. To examine predictors (e.g. demographic, environmental, family history,
mucosal, microbiological and immunological characteristics) for the (absence
of) prophylactic treatment effect
3. To examine whether cessation of antibiotic prophylactic treatment affects
the presence of RTI symptoms and how this correlates with clinical,
microbiological and immunological characteristics of the patients.
4. To record and evaluate adverse events:
- The occurrence of mild adverse effects as described in the Summary of Product
Characteristics (SPC), such as skin rash, gastro-intestinal complaints,
pruritus or mild headache;
- The occurrence of severe adverse reactions.
5. To examine short-term and long-term effects of co-trimoxazole prophylaxis on
microbiota deviation, AMR and (mucosal and systemic) immunological outcomes.
Study design
Randomized double-blind placebo-controlled clinical trial comparing
co-trimoxazole with placebo treatment given for 3 months in children with
recurrent RTIs.
Intervention
One group receives co-trimoxazole 18mg/kg twice daily (36mg/kg/day) and the
other group receives a placebo twice daily.
Study burden and risks
The study may result in minor (well known) side effects caused by the
antibiotics as well as a positive effect with reduction in days with
respiratory symptoms in this subgroup. The subject of the study is specifically
for young children (<=10 years) since RTIs are most common among this population
and antibiotic prophylaxis is prescribed frequently for this specific
indication in children despite lack of evidence.
Els Borst-Eilersplein 275
Den Haag 2545 AA
NL
Els Borst-Eilersplein 275
Den Haag 2545 AA
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria: - Presenting to one of the participating clinics; -
Age 6 months - 10 years; - Suffering from recurrent respiratory tract
infections (RTIs); - Informed consent from parent(s)/caregiver(s) with legal
custody. For age-specific definitions of recurrent RTIs, we took cut-offs as
defined by the Dutch Society of Pediatric except for children aged 5-10 years
in whom we used the same definition as younger children (2-5 years). This means
yearly at least 11 and 8 parental-reported upper RTIs including, but not
limited to, otitis media for children aged <2 and 2-10 years respectively.
Recurrent lower RTIs (i.e. pneumonia, bronchopneumonia or acute bronchitis) are
defined as at least 2 episodes per year or 3 or more episodes during the
child*s life regardless of age.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Current prophylactic antibiotic use or prophylactic antibiotic use during the
previous month;
- Underlying immune deficiency other than for IgA or IgG subclasses;
- Congenital abnormalities (including cleft palate, neuromuscular, cardial and
syndromal disorders, hematologic disorders;
- Suffering from chronic respiratory disease, such as cystic fibrosis (CF),
primary ciliary dyskinesia (PCD) or anatomical abnormalities;
- Children who only suffer from recurrent acute otitis media or chronic
suppurative otitis media will be excluded since antibiotic prophylaxis has
proven to be beneficial for this group;
- Known allergy to co-trimoxazole;
- Known contra-indication for co-trimoxazole, e.g. liver failure, impaired
kidney function and/or hematologic disorders.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003164-13-NL |
| CCMO | NL63954.098.17 |