The aim of the CO-PRINCE study is to establish the efficacy and safety of long-term antibiotic prophylaxis with co-trimoxazolein children with recurrent upper and/or lower respiratory tract infections (including ear-nose-throat (ENT)).
ID
Source
Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Infection frequency per person month.
Secondary outcome
Quality of life, emergence of antibiotic resistance in the commensal flora or
in a disease-causing isolated bacterium, side effects, cost-effectiveness.
Background summary
Many children suffer from recurrent respiratory infections: according to
hospital registry data (DBC codes) 5000-6000 of these
children per year are being followed by a pediatrician. This leads to absence
from day-care or school (the children) or work (the
parents). Currently, Dutch pediatricians and ENT-surgeons often use
co-trimoxazole prophylaxis in these children, with
considerable variability in how these children are treated (dosage, duration)
and monitored (laboratory evaluation, drug levels).
This use is off-label, and may also lead to an increased carriage of
microorganisms with antibiotic resistance in the population.
Data in the literature are limited, but indicate a possible effect that may
wane with long-term use.
If shown beneficial, wider use of co-trimoxazole prophylaxis can diminish
absence from school (the children) and work (the
parents), and increase their quality of life.
Study objective
The aim of the CO-PRINCE study is to establish the efficacy and safety of
long-term antibiotic prophylaxis with co-trimoxazole
in children with recurrent upper and/or lower respiratory tract infections
(including ear-nose-throat (ENT)).
Study design
We will compare long-term use (from the moment of inclusion until the end of
April (the *cold season*) or during 3 consecutive months, whichever is longer)
of 18mg/kg co-trimoxazole (3mg trimethoprim + 15mg sulfamethoxazole) bid to
placebo in 170 children (>6 months and <18 years) in a multi-center randomized
double blind trial. The primary outcome is infection frequency per person
month. Secondary outcomes are quality of life, frequency of carriage of
microorganisms with antibiotic resistance, side effects, and cost-effectiveness.
The CO-PRINCE study consortium is a unique cooperative network that brings
general and university pediatric, pharmacological, and ENT-expertise together
and is supported by the Medicines for Children Research Network (MCRN),
ensuring quality and feasibility.
Intervention
18mg/kg co-trimoxazole (3mg trimethoprim + 15mg sulfamethoxazole) bid, until
the month of April (inclusive) or during 3 months, whichever is longer (to
prevent stopping the medication during the 'cold season').
Study burden and risks
Co-trimoxazole has been used for >35 years, also in children. So, no other
risks than -relatively rare- known side effects are expected. The study burden
comprises taking the study medication, either co-trimoxazole or placebo. Right
now, children with recurrent respiratory infections are often treated with
co-trimoxazole prophylaxis, resulting in either no extra burden by entering the
study (co-trimoxazole would be used anyway) or taking the study medication 2
times a day. Besides that, doctors visits will take a little longer because of
the study visits, and 2-4 extra venepunctures will be performed during the
entire study. If separate informed consent is given, nasopharyngeal swabs and
fecal samples will be collected in a subgroup every 3 months. The expected
benefit on the one hand and limited burden and risks on the other hand are well
balanced.
Postbus 90153
5200ME `s-Hertogenbosch
NL
Postbus 90153
5200ME `s-Hertogenbosch
NL
Listed location countries
Age
Inclusion criteria
Children >6 months and <18 years with recurrent respiratory infections visiting pediatricians and ENT-surgeons in participating hospitals will be included if informed consent is obtained from the parents, and children (if >11 years). Definition of 'recurrent' respiratory infections: >=3 respiratory infections in the 6 months preceding study entry or start of the current therapy, or >=4 per year (documented by a doctor and treated with antibiotics).
Exclusion criteria
- known primary immunodeficiency (e.g. CVID, a/hypogammaglobulinemia);
- known secondary immunodeficiency (e.g. HIV, chemotherapy, transplantation);
- eponymous syndromes;
- chromosomal abnormalities;
- cleft palate;
- renal or hepatic insufficiency;
- known glucose-6-phosphate deficiency, cystic fibrosis, primary ciliary dyskinesia or acute porphyria;
- children using drugs known to interact with co-trimoxazole;
- children with previous allergic reaction to co-trimoxazole.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-019170-33-NL |
| CCMO | NL31724.028.10 |