Status Asthmaticus on the PICU; Intravenous Salbutamol

Study Overview
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Brief Summary
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Although IV salbutamol is frequently used in children in a wide range, pharmacodynamic data are scarce. To date, there is an insufficient evidence base to guide initial and subsequent dosing recommendation for its IV use in children. Especially the need for a loading dose needs to be addressed. Therefore, pharmacodynamic and kinetic data are needed to guide initial dosing strategies of IV salbutamol in children. To assess the efficacy of a loading dose of intravenous salbutamol in children admitted to a PICU for severe acute wheeze or severe acute asthma. Efficacy is measured by the reduction in asthma score (Qureshi) at 1 hour after administration of the loading dose, compared to placebo.

Official Title
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Efficacy of a Loading Dose of IV Salbutamol in Children Admitted to a PICU for Severe Acute Asthma or Severe Acute Wheeze

Conditions
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Childhood Asthma With Status Asthmaticus

Intervention / Treatment
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* Drug: Salbutamol
* Drug: Sodium Chloride 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 2-18 years of age at moment of inclusion Admitted to PICU for Severe Acute Asthma or Severe acute (viral) wheeze Requiring administration of IV salbutamol Exclusion Criteria: Patient is outside of specified age range Patient has already received a -loading dose- of IV salbutamol in the general hospital Lower airway infection with consolidation on a chest X ray -Patient has Down's Syndrome Patient has a congenital/acquired heart defect that interferes with normal asthma treatment Patient has a primary/secondary immunodeficiency Patient has a pre-existing chronic pulmonary condition, known to mimic asthma: Cystic fibrosis, Bronchopulmonary dysplasia, Bronchiolitis obliterans

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salbutamol loading dose<br>Salbutamol loading dose of 15 mcg/kg in 10 minutes, with a maximum of 750 mcg. | Drug: Salbutamol<br>* Intravenous Salbutamol loading dose<br>|
| Placebo Comparator: Sodium Chloride 0.9%<br>10 ml of Sodium Chloride 0.9% in 10 minutes. | Drug: Sodium Chloride 0.9%<br>* 10 ml of Sodium Chloride 0.9% in 10 minutes intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction Asthma score | The primary outcome variable is (reduction of) asthma score (Qureshi) 1 hour after administration of loading dose in the intervention group compared to the placebo group. Based on expert opinion, we consider a reduction of 2 points to represent a clinically relevant improvement. | First 24 hours after admission on the PICU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative dose of IV salbutamol |  | Through study completion, an average 48 hours | 
| Maximum infusion rate of IV salbutamol in mcg/kg/min |  | Through study completion, an average 48 hours | 
| Total duration of IV salbutamol treatment in hours |  | Through study completion, an average 48 hours | 
| Occurrence/frequency of side effects |  | Through study completion, an average 48 hours | 
| Length of Stay on PICU in days |  | Through study completion, an average 72 hours | 
| Use of co-medication |  | Through study completion, an average 72 hours | 
| Use of/duration of non-invasive mechanical ventilation in days |  | Through study completion, an average 72 hours | 
| DNA polymorphism of the ADRB2-receptor gene | The investigators will look at DNA, if there is a polymorphism in the ADRB2-receptor gene. If there is a polymorphism it can cause downregulation of the adrenergic B2 receptors. | Through study completion, an average 1 year | 
| Use of/duration of non-invasive/invasive mechanical ventilation in days |  | Through study completion, an average 72 hours |