Clinical trial
Pharmacogenetics Use For Further Treatment Improvement in childreN
Name
NL63849.018.17
Description
There is large heterogeneity in treatment response to asthma medication and a one-size fits all approach based on current guidelines might not fit all children with asthma. It is expected that children with one or more variant alleles (Arg16Arg and Arg16Gly) within the beta2 adrenergic receptor (ADRB2) gene coding for the beta2-receptor have a higher risk to poorly respond to long-acting beta2-agonists (LABA) comparing to the Gly16Gly wildtype.
Aims To study whether ADRB2 genotype-guided treatment will lead to improvement in asthma control in children with uncontrolled asthma on inhaled corticosteroids compared with usual care.
Design A multicentre, double-blind, precision medicine, randomized trial will be carried out within 20 Dutch hospitals. 310 asthmatic children (6-17 years of age) not well controlled on a low dose of inhaled corticosteroids (ICS) will be included and randomized over a genotype-guided and a non-genotype-guided(control) arm. In the genotype-guided arm children with Arg16Arg and Arg16Gly will be treated with double dosages of ICS and with the Gly16Gly wildtype with add on LABA. In the control arm children will be randomized over both treatment options. Lung function measurements, questionnaires focussing on asthma control (ACT/c-ACT) and quality of life, will be obtained in three visits within 6 months. The primary outcome will be improvement in asthma control based on repeated measurement analysis of c-ACT or ACT scores in the first three months of the trial. Additional cost effectiveness studies will be performed.
Conclusion Currently, pharmacogenetics is not used in paediatric asthmas. This trial may pave the way to implement promising results for genotype-guided treatment in paediatric asthma in clinical practice.
Trial arms
Trial start
2018-06-12
Estimated PCD
2023-10-18
Trial end
2023-10-18
Status
Completed
Treatment
ADRB2-genotype guided treatment
This intervention assesses whether ADRB2 genotype-guided treatment leads to better asthma control after 3 months compared to usual care in children who are uncontrolled despite adherent and adequate use of ICS.
Arms:
ADRB2-genotype guided treatment arm
Randomisation
In the control arm, children will be randomised over double dose ICS or ICS+LABA instead of treatment according to their genotype.
Arms:
Control arm
Size
102
Primary endpoint
Asthma control based on (childhood-)Asthma Control Test scores in the first 3 months of the trial
3 months
Eligibility criteria
Inclusion Criteria:
* Doctor's diagnosis of asthma (ever) based on patient history, FEV1 reversibility ≥ 12% and/or bronchial hyperresponsiveness
* Current asthma symptoms (based on ACT (≥12 years) or C-ACT (\<12 years) score ≤ 19
* ICS use ≥ 3 months before inclusion (start dosage ICS, treatment step 2 according to childhood asthma guideline NVK, Table 3)
* Adequate inhalation technique (based on validated checklist score \[21\])
* Self-assessed good adherence to maintenance asthma treatment
* Understanding of Dutch language
* Internet access a home, willing to fill in internet questionnaires
Exclusion Criteria:
* Active smoking
* Congenital heart disease
* Serious lung disease other than asthma (Cystic Fibrosis, Primary Ciliary Dyskinesia, congenital lung disorders, severe immune disorders)
* LABA use in past 6 months
* Omalizumab use
* ICU admission in the previous year
Protocol
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Updated at
2023-11-07
1 organization
1 product
1 indication
Indication
Asthma in Children