Title: Three days vs five days oral cotrimoxazole therapy in nonsevere pneumonia
1Three days vs five days oral cotrimoxazole
therapy in non-severe pneumonia
Kartasasmita C, Samir K. Saha and Cotrimoxazole
Study Group Indonesia and Bangladesh.
2Back ground
- WHO recommendation for Non-Severe pneumonia.
- Cotrimoxazole or Amoxicillin for 5 days
- Attention to shorter course of therapy
- Better understanding about the role of antibiotic
- ICDDR,B experience with drop-outs
- Pakistan experience with Short course amoxicillin
therapy. - Implications on Compliance, Cost and Microbial
resistance.
3Aims
- To determine the equivalence of 3 and 5 days of
oral Cotrimoxazole for the treatment of non
severe pneumonia. - To study the impact of cotrimoxazole treatment on
carriage strains of Streptococcus pneumoniae and
Haemophilus influenzae.
4Study design
- Double blind, Randomized, Placebo-controlled
equivalence trial. - Study was conducted form July 2001 to May 2003.
- Ethical clearance was obtained from the ERC of
Bangladesh Institute of Child Health and Hasan
Sadikin General Hospital.
5Screening of Patients
- Exclusion criteria
- Having severe pneumonia or other very severe
disease - Allergic to cotrimoxazole
- Acute Asthma
- Prior enrollment in the study.
- Required antibiotic for any other disease(s)
- Previous hospitalization in last two weeks.
- Prior antibiotic
- Weight lt4.0 kg
- Inclusion criteria
- Age 2-59 months
- WHO defined non-severe pneumonia with or without
wheezing. - Consent given
6Enrollment of patients
- Baseline assessment
- Demographic information
- Clinical examination
- Randomization
- Done in 3 unequal blocks of 4, 6 8 in a larger
block of 18. - Provided with unique ID
- NP swab to isolate Spn and Hi.
7Study Medicine
- Two bottles for each patients
- Blue cap 1st three days
- Contained cotrimoxazole
- 1st dose given at health care
- White Cap Last two days
- Contained either contrimoxazole (5 days group) or
placebo (3 days group).
8Follow up
- Follow up on day 3, and 5 15.
- Children were assessed clinically
- Compliance to therapy was recorded.
- Drug consumption gt80
- Not missed gt1 dose
- Outcome recorded
- Resolved on day 3 5
- Failed day 3 5
- Relapsed day 15
- 2nd NP swab was collected on day 15.
9Outcome of treatment
- Treatment failure on day 3 (any two of the
following) - RR is not reduced by ?5
- Temp not reduced by ?10C
- Mother/caregiver mentioned that baby has
deteriorated. - Treatment failure on day 5
- RR is fast
- Chest in-drawing
- Other danger sign(s)
- Relapse Day 15
- Development of pneumonia again by 15 day.
- Clinically resolved
- RR ?age specific cut offs
- No danger sign
10Analysis
- Sample size 1000 under five non severe pneumonia
cases at each site. - Data were double entered and verified in EPI Info
6. - Final analysis was done using EPI Info 6 and SPSS
11.0
11Demographic Indicators and Clinical Signs
12Number randomized (2022)
Day 5 N 1014
Day 3 N 1008
Intention to treat analysis
Number excluded - Lost to follow
up D5 (LFU) only (63) - Protocol
violation (PV) only (44) Combination LFU
and PV (22)
Number excluded - Lost to follow
up D5 (LFU) only (82) - Protocol
violation (PV) only (44) - Combination
LFU and PV ( 16)
Number futher analyzed (879)
Number futher analyzed (872)
Day 3 Followup
Per Protocol analysis
Number failed therapy/died 12/0
Number failed therapy/died 18/0
Number improved (867)
Number improved (854)
Day 5 Followup
Number failed therapy/died 68/0
Number failed therapy/died 64/1
Number resolved (799)
Number resolved (790)
Day 15 Follow-up
Number relapsed (55)
Number relapsed (62)
Number cured (735)
Number cured (737)
13Summary Results Per Protocol Analysis
14Impact of treatment Per protocol
15Conclusions
- Cotrimoxazole therapy for 3 and 5 days are
equivalent. - Treatment with cotrimoxazole increases the
nonsusceptibility of NP carriage strains. - Impact of treatment on carriage strains are
similar in both the groups. - As a whole, short course cotrimoxazole is
effective in a population with high rate of in
vitro cotrimoxazole non susceptible Spn and Hi.
16COTRIMOXAZOLE STUDY GROUP MEMBERS
- INDONESIA
- Cissy B. K
- Dwi Agustian
- Chrysanti
- Ni Sayu Dewi
- Maula Rifada
- Anglita
- Vidi Permatagalih
- Sri Yusnita
- BANGLADESH
- Samir K. Saha
- Nawshad
- M. Hanif
- M. Ruhulamin
- Billal Hossain
- Rafeza Khanam
- Tanima Sharmin
- Maksuda Islam
- Abdullah-Al-Mahin
- Masoodul Haque
- Shams-el Arifeen
CONSULTANTS Eric Simoes, MD. Shamim Qazi, WHO