Public Assessment Report for paediatric studies submitted in ...

Assessor’s comment
The sample size is small and 8 subjects could not be assessed by peak expiratory flow. The study
design was poor as the assessment of clinical status was not assessed as accurately as other
measurements. These facts limit the significance of the findings.
The study was very old (1984) and the latest paediatric guidelines (2009) do not provide any
information about these routes of administration in acute exacerbation of asthma. These routes of
administration of salbutamol might be of little clinical importance in such cases.
The reported adverse events are known to be associated with the use of salbutamol (increase of
heart rate and blood pressure) and not very well investigated (eg ECG); there was no report of a new
one.
There isn’t any document to certify that the study has been conducted in accordance with GCP.
In conclusion, this study does not provide robust evidence on the efficacy and safety of
intramuscular or subcutaneous salbutamol administrated in a dose of 8 µg/kg to children with an acute
exacerbation of asthma.
Study D78/B24
A comparison of intravenous salbutamol, aminophyline and the combination in the treatment of
acute severe asthma in children
Objective - to compare the effectiveness of continuous intravenous infusion of either salbutamol,
amonophylline or the combination of both drugs in the treatment of acute severe asthma in children.
Study population - 64 children (44 males), aged 3.9-14.8 (mean 8.1 years), with acute severe
asthma.
Study design - the patients were randomly allocated to one of 3 treatment groups: salbutamol,
aminophylline or a combination of salbutamol plus aminophylline.
All patients had basic details recorded and were examined. Before starting treatment, their
clinical status was assessed using a scoring system, 0-3 for normal, mild, moderate and severe respectively
for each of four signs: rib recession, breath sound intensity, rhonchi and rales.
A sample of arterial blood was taken for measurement of pH, pO2 and pCO2. Venous blood was
taken for serum potassium and, in some, plasma salbutamol.
Heart rate was measured from was measured from electrocardiographic (ECG) trace and peak
expiratory flow rate (PEFR) with a Wright peak flow meter.
Clinical score and PEFR were reassessed at 1, 2, 4, 6, 12 and 18h after the start of infusion.
Arterial pH and blood gases were repeated at 6 and 18h. Theophylline concentration was measured at 6h
or if therapy was to be changed on clinical grounds.
Treatments - the dosage of aminophylline consisted of a loading dose of 5.6 mg/kg infused over
15 to 30 minutes followed by a continuous infusion of 1 mg/kg/min.
The proposed salbutamol dosage consisted of increasing the flow rates up to 1.6 µg/kg/min or
until relief was seen or heart rate reached 160-180 beats/min.
At 4 hours, when patients were reassessed, intravenous hydrocortisone could be added if
response was regarded as sluggish. The dosage consisted of a 4 mg/kg loading dose followed by 3 mg/kg
every 3 hours. If response was satisfactory at 4h but not at 6h or subsequently, hydrocortisone could be
started at those times.
If after hydrocortisone had been added, response was still not regarded as satisfactory at a
subsequent assessment either salbutamol or aminophylline could be added so that all three drugs were
used. All intravenous drugs were given using a constant rate infusion pump.
Statistical methods
The chi square test was used whenever appropriate for dichotomous data, but Fisher’s exact test
was used for small expected frequencies. The probability values were those for the two tailed tests.
Results
There was a preponderance of males, 44 (69%). The distribution of patients between the 3
treatment groups was the following: 19 patients were treated with salbutamol, 25 patients were treated
with aminophylline and 20 patients were treated with the combination.
Salbutamol Final Public Assessment Report
RO/W/0001/pdWS/001
Page 44/76