Three days vs five days oral cotrimoxazole therapy in nonsevere pneumonia

1
Three days vs five days oral cotrimoxazole
therapy in non-severe pneumonia
Kartasasmita C, Samir K. Saha and Cotrimoxazole
Study Group Indonesia and Bangladesh.
2
Back 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.

3
Aims

• 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.

4
Study 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.

5
Screening 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

6
Enrollment 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.

7
Study 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).

8
Follow 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.

9
Outcome 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

10
Analysis

• 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

11
Demographic Indicators and Clinical Signs
12
Number 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)  
 
13
Summary Results Per Protocol Analysis
14
Impact of treatment Per protocol
15
Conclusions

• 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.

16
COTRIMOXAZOLE 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