Randomized comparative

trial of efficacy of
paracetamol, ibuprofen and
paracetamol-ibuprofen
combination for treatment
of febrile children
Critical Appraisal for Therapy Articles

Fermana Saputra, dr.
What question did the study ask?
P=Patients
pasien anak dengan demam tanpa komplikasi
I=Intervention
pengobatan dengan paracetamol
C=Comparison
pengobatan dengan ibuprofen
pengobatan dengan kombinasi paracetamol-
ibuprofen
O=Outcome
lebih cepat menurunkan panas

Apakah pengobatan dengan paracetamol pada
pasien anak dengan demam tanpa komplikasi lebih
cepat dalam menurunkan panas dibandingkan
pengobatan dengan ibuprofen, atau dengan
kombinasinya?
Was the assignment of patients to
treatments randomised?
This was investigator blind,
randomized, parallel group, multiple
arm comparative, single dose trial
carried out at Pediatrics department of a
tertiary care teaching hospital.

Yes, randomized
Based on computer generated
randomization, block randomization
was used to assign three sequences to
33 subjects in each group in the ratio of
1:1:1.
Were the groups similar at the start
of the trial?

Terdapat group baseline yg hampir sama pada
weight, height, dan baseline temperature
Baseline age dan gender tidak terlalu sama
Secara statistik tidak signifikan, karena p>0.05
Aside from the allocated treatment, were
groups treated equally?
For ibuprofen 10 mg/kg or paracetamol 15
mg/kg or both ibuprofen and paracetamol,
with the help of calibrated measuring cylinder
with 60 ml of water.
Primary study objective was the reduction in
the tympanic temperature from the baseline
temperature at the end of 4 h after drug
administration.
Afebrile children at 1, 2, 3 and 4 h post dose,
any adverse drug events occurring during the
4 h period were recorded.

Yes, differrent groups were treated
equally.
Were all patients who entered the trial accounted
for? and were they analysed in the groups to
which they were randomised?
Tiap grup terdiri dari 33 pasien
Grup PCT, 2 anak loss follow up, 1 anak
withdrawn dengan consent (9%)
Grup ibuprofen, 1 anak loss follow up
(3%)
Grup kombinasi, 2 anak loss follow up
(6%)

Loss follow up masih minimal, < 20%

Tidak disampaikan alasan untuk loss
follow up, hanya diberikan kriteria inklusi,
eksklusi, dan withdrawn.
Were measures objective or were the patients and
clinicians kept blind to which treatment was being
received?
This was investigator blind.
Participants were allocated by the
unblinded investigator to one of the
three treatment arms.

Double blind design would have been
ideal but would have been complicated
and not likely to be acceptable by
participants hence investigator blind
design was considered.
WHAT WERE THE
RESULTS?
How large was the treatment
effect?
There was a significant difference between three
groups (P = 0.013), maximum reduction in
temperature in combination group and
minimum in paracetamol group.
Post-hoc multiple comparison
test between the three groups
Untuk menghitung relative risk
Antara PCT-Ibuprofen, PCT-
Kombinasi, Ibuprofen-Kombinasi

Persentase pasien menjadi afebris
setelah 4 jam di tiap grup:
PCT: 76.66 %
Ibuprofen: 78.12 %
Kombinasi: 93.54 %

Between paracetamol and
combination group (P = 0.03)
Pasien menjadi afebris setelah 4 jam
RR = T/K = 0.93/ 0.76 = 1.22
Since the RR > 1, the treatment increases the
afebrile patients.
ARR = K-T = -0.17
The absolute benefit of treatment is a 17%
increase in afebrile patients.
RRR = 1-RR = -0.22
The treatment increase the afebrile patient by
22% relative to that occurring in the
PCT/control group.
NNT = 1/ARR = -5.88
No significant difference between
ibuprofen and the combination group (P
= 0.167), or
Between paracetamol and ibuprofen
group (P = 0.102).
How precise was the estimate
of the treatment effect?
In this study, the difference in
temperature reduction between two
groups (PCT & Combination) although
statistically significant (P = 0.013), was
not clinically significant less than 1C
(0.71C).
2.19 1.48 = 0.71 C

CI [?]
Will the results help me in
caring for my patient?
Is my patient so different to those in
the study that the results cannot
apply?
No, it isnt
This study population is Indian children

Is the treatment feasible in my setting?
Yes, it is
Walaupun sediaan kombinasi PCT-
Ibuprofen dengan dosis yg disesuaikan
belum tersedia [?]

Will the potential benefits of treatment
outweigh the potential harms of
treatment for my patient?
Yes, it will
If quicker reduction in body temperature is
the goal of therapy.

Both antipyretics have been found to be
equally safe in children.[9]
PCT should be used preferentially due to a
lower risk of adverse effects.[6,10]
Ibuprofen has the advantage of less frequent
dose (every 6-8 h vs. every 4 h for PCT).[11]