Transcript Poster presentation

Indiaclen Short course of Amoxicillin in
treatment of Pneumonia
(ISCAP)
3 versus 5 days amoxicillin for treatment of
non-severe pneumonia in young children: a
double blind, placebo controlled multi-centric
randomized trial
Funding Agency
USAID through IndiaClen/INCLEN
Study Location
-
Mumbai
- Lucknow
- Nagpur
- New Delhi
- Chandigarh
- Trivandrum
- Vellore
C
N.D
L
N
M
T
V
C=Chandigarh
N.D= N. Delhi,
L=Lucknow,
N=Nagpur,
M=Mumbai,
T=Trivendrum,
V=Vellore
BACKGROUND
• ARI is the biggest killer of under 5 children in developing
countries including India.
• ARI Control Programme in India recommends
cotrimoxazole as first line drug for non-severe pneumonia.
• Reports of significant in vivo and in vitro resistance to
cotrimoxazole.
• Clinical studies showing high treatment failure with
cotrimoxazole.
Objectives
Primary
To compare the proportions of children
recovering on 3-day versus 5-day treatment
with oral amoxicillin in children aged 2-59
months presenting with non-severe pneumonia,
with or without wheeze
Objectives
Secondary
To compare
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Proportion who relapse within the next 6-14 days of
observation
Proportion who had resistant strains of S.pneumoniae
and H.influenzae in nasopharyngeal cultures at the time
of enrollment and at 12-14 days follow-up
Direct medical cost of treatment of clinical failures and
relapses in both groups (Data not shown)
Outcome Measures
Clinical Cure- on day 6
 Clinical failure- Till day 6
 Clinical relapse days 7-14

DEFINITIONS
Clinical cure:
Return of respiratory rate to age specific WHO cut off.
Clinical Failure:
Development of chest indrawing with danger signs or
persistence of fast breathing at day 3 or later leading to
therapy change.
Relapse:
Development of signs of pneumonia between day 6 -14.
Inclusion Criteria
Children aged 2 - 59 months
 with non-severe pneumonia (WHO defined)
 Written informed consent

Exclusion criteria
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



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
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severe pneumonia or very severe disease (WHO defined)
severe malnutrition
other infectious conditions requiring antibiotics therapy
clinically recognized congenital heart disease
known or clinically recognized chronic systemic disorder
history of repeated wheezing including physicians
diagnosed asthma
hospitalization in past 2 weeks
use of antibiotics in previous 2 days
measles within the last month
known history of penicillin allergy
prior enrollment in the study
Sample Size
 Calculated to test equivalence hypothesis to detect
difference of 4.5% using one sided t- test and 90%
power, assuming 12% failure rate with amoxycillin
 Required number of patients was 950 in each group

Intervention
Scored amoxicillin dispersible tablet (125 mg/tablet) for
the first three days
4-6 kg
½ tablet per dose
7-10 kg
1 tablet per dose
11-15 kg
1 ½ tablets per dose
16-20 kg
2 tablets per dose
Effective dose per kg body weight – 31 to 54 mg/day

For the next two days they received either amoxicillin or
placebo
FINAL OUTCOME
3 days = 1095
5 days = 1093
1st follow-up
Failure = 68
Resolved = 1027
Failure =73
Resolved = 1020
Resolved = 983
2nd follow-up
Failure= 47
Resolved = 980
Failure= 37
Relapse=32
Cured = 948
Relapse= 29
3rd follow-up
Cured = 954
Results
Table 1: Loss to follow-up
3 day
AMX
N
%
5 day
Total
AMX
N
% N
%
Absolute
difference,
C.I
LTF Day 4
37
3.4 43
3.9 80
3.7 0.5
(-1, 2.0)
LTF Day 6
62
5.7 67
6.1 129
5.9 0.4
(-1.5, 2.4)
LTF Day
12-14
96
9.8 94
8.6 190
8.7 0.2
(-2.2, 2.5)
Results
Table 2: Adherence to treatment types
3-day
AMX n %
5-day
AMX n %
Total
n%
p-value
Adherence
at 3 day
1031
94.2
1026
93.9
2057
94
0.78
Adherence
at 5 day
937
85.6
928
84.9
1865
85.2
0.66
Results
Table 3: Outcome Measures (Per Protocol)
N
3-day
AMX
%
N
5-day
AMX
%
Absolute
Difference
95% C.I
Total recruited
1033
1026
Cure on day 6
980
94.9
983
95.8
0.9
(-0.9, 2.8)
Relapse
32
3.3
29
3.0
0.3
(-1.2, 1.85)
Results
Table 5: Risk factors associated with failures by logistic
analysis
Variable
Adjusted OR
C.I
Unadjusted OR
C.I
Excess Respiratory
Rate more than 10
bmp
2.82
2.8
(1.8, 4.45)
(1.5, 5.2)
Non-Adherence at 5
days
11.57
(7.4, 18.0)
-
RSV positivity
1.95
(1.0, 3.8)
13.1
(8.5, 20.2)
2.1
(.9, 4.9)
SP resistant
Time 0
SP resistant
Time 2
3 day AMX
HI resistant
Time 0
5 day AMX
62.2
57.4
61.2
54.4
78.2
66.7
66.1
100
80
60
40
20
0
66.6
Resistance pattern of isolates in two treatment types
HI resistant
Time 2
CONCLUSIONS
1. Oral amoxicillin for 3 days is as effective
clinically as 5 days in the treatment of
children 2-59 months old suffering from
non severe pneumonia.
2. In S. pneumoniae on day 12 – 14 an
increased in-vitro resistance to
cotrimoxazole with 5 day treatment seen.
RECOMMENDATIONS
For the treatment of non-severe
pneumonia in children 2 to 59
months of age the National
ARI Control Programmes
already using amoxicillin as
first line drug should consider
3 day antibiotic therapy