|- candidate number||28973|
|- NTR Number||NTR7249|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||31-mei-2018|
|- Secondary IDs||18-008 MEC-nr |
|- Public Title||Antibiotic prophylaxis for children with recurrent respiratory infections: towards evidence-based guidelines|
|- Scientific Title||Antibiotic prophylaxis for children with recurrent respiratory infections: towards evidence-based guidelines|
|- ACRONYM||APPROACH study|
|- hypothesis||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. |
|- Healt Condition(s) or Problem(s) studied||Respiratoiry tract infections, Children, Respiratory tract infection|
|- 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 – 5 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 Pediatrics, i.e. yearly at least 11 and 8 parental-reported upper RTIs including, but not limited to, otitis media for children aged <2 and 2-5 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.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jul-2018|
|- planned closingdate||1-mrt-2022|
|- Target number of participants||158|
|- Interventions||Children will be randomized to one of 2 oral regimens for 3 months: co-trimoxazole 36 mg/kg/day (2 x 18 mg/kg) (n=79) or placebo twice daily (n=79).|
|- 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 proportionate reduction in days with RTI symptoms will be calculated from baseline to 3 months after inclusion. |
|- Secondary outcome||1. Outcomes related to the hypothesis that co-trimoxazole prophylactic therapy is effective in the prevention of recurrent RTIs: e.g. tme to resolution of symptoms, change in symptomatic RTI burden after cessation of antibiotic prophylaxis|
2. To evaluate clinical, microbiological and immunological patient characteristics of subgroups with either prophylaxis failure or prophylaxis benefit and with varying symptomatic disease burden after prophylaxis/placebo initiation.
3. The effect of co-trimoxazole treatment on the microbial composition and AMR in the respiratory and intestinal tract during and after treatment
|- Timepoints||T=0: Screening for inclusion, start trial medication, collection of samples, questionnaire and start daily diary|
T=1 month: sample collection, monthly questtionaire (repeats every month)
T=3 months: stop trial medication, lab tests, sample collection
T=6 months: sample collection, stop diary, last questionnaire.
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES|| D. Peeters|
|- CONTACT for SCIENTIFIC QUERIES|| D. Peeters|
|- Sponsor/Initiator ||University Medical Center Utrecht (UMCU), Juliana Children's Hospital/Haga Hospital|
(Source(s) of Monetary or Material Support)
|Juliana Children's Hospital, University Medical Center Utrecht (UMCU)|
|- Brief summary||Rationale: 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. |
Objective: Primary: To determine whether antibiotic prophylaxis is more effective than placebo in prevention of respiratory symptoms in children with recurrent RTIs. Secondary: 1. To identify microbiological and clinical patient characteristics of prophylaxis failure and benefit. 2. To determine short-term and long-term effects of co-trimoxazole on microbiome deviation, antibiotic resistance and the child’s immune system.
Study design: Randomized double-blind placebo-controlled clinical trial comparing co-trimoxazole with placebo treatment given for 3 months in children with recurrent RTIs.
Study population: A total of 158 children (aged 6 months – 5 years) presenting to one of the participating hospitals with recurrent RTIs and fulfilling inclusion criteria.
Intervention: One group receives co-trimoxazole 18mg/kg twice daily (36mg/kg/day) and the other group receives a placebo twice daily.
Main study parameters/endpoints: Primary: The number of days with respiratory symptoms from baseline to 3 months after inclusion. Secondary: The number of days with respiratory symptoms from baseline to 6 months after inclusion, microbiome deviation and antibiotic resistance of nasopharyngeal and gut bacteria.
|- Main changes (audit trail)|
|- RECORD||31-mei-2018 - 13-jun-2018|