A1260612903krUsS

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• 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

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Study Location

• - Mumbai
• - Lucknow
• - Nagpur
• - New Delhi
• - Chandigarh
• - Trivandrum
• - Vellore

C
N.D
L
N
M
CChandigarh N.D N. Delhi, LLucknow, NNagpur,
MMumbai, TTrivendrum, VVellore
T
V
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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.

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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

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Objectives

• Secondary
• To compare
• 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)

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Outcome Measures

• Clinical Cure- on day 6
• Clinical failure- Till day 6
• Clinical relapse days 7-14

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DEFINITIONS
Clinical cure Return of respiratory rate to age
specific WHO cut off. Clinical Failure Developmen
t 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.
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• Inclusion Criteria
• Children aged 2 - 59 months
• with non-severe pneumonia (WHO defined)
• Written informed consent

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• Exclusion criteria
• 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

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• 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

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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

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FINAL OUTCOME
3 days 1095
5 days 1093
1st follow-up
Failure 73
Failure 68
Resolved 1027
Resolved 1020
2nd follow-up
Failure 47
Resolved 983
Resolved 980
Failure 37
Relapse32
Cured 948
3rd follow-up
Relapse 29
Cured 954
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ResultsTable 1 Loss to follow-up
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ResultsTable 2 Adherence to treatment types
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ResultsTable 3 Outcome Measures (Per Protocol)
3-day AMX N 5-day AMX N 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)
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ResultsTable 5 Risk factors associated with
failures by logistic analysis
13.1 (8.5, 20.2)
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Resistance pattern of isolates in two treatment
types
P value 0.01
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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.
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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