Randomized Trial of Amoxicillin Versus Placebo for (Fast Breathing) Pneumonia
Condition: Pneumonia; Tachypnea
MeSH terms: Pneumonia; Tachypnea
Study type: Interventional

Summary: 
      The relative benefits and risks of antibiotic therapy in WHO defined fast breathing pneumonia
      in pre-school children in resource limited settings are controversial both at an individual
      and public health level. Most infections are viral or self-limiting and non-selective drug
      treatment has contributed to the global epidemic of antibiotic resistance. There is no high
      quality trial evidence in managing children with fast breathing in community settings and the
      WHO itself has called for evidence on which to update guidance. The investigators proposed
      non inferiority trial comparing standard antibiotic treatment with placebo in poor urban slum
      settings in South Asia to address this deficit.
    

Detailed description: 
      Pneumonia is a major cause of illness and death in children in low-income countries. With a
      view to decreasing death from pneumonia, the World Health Organization and UNICEF developed
      the Integrated Management of Childhood Illness (IMCI) algorithm which simplifies management
      of common childhood illnesses such as pneumonia and diarrhea into different levels of
      severity for determining the most appropriate case management by primary healthcare
      providers. Many pneumonia cases are categorized as non-severe pneumonia (defined as fast
      breathing above the specified age cut-off for respiratory rates). As there is incomplete
      information regarding the cause of this type of "pneumonia" from primary care settings,
      treatment guidelines by WHO are dictated by culture information from hospital pneumonia cases
      which are different in severity and cause. Current WHO guidelines advocate the use of oral
      antibiotics for fast breathing pneumonia. However, it is postulated that most fast breathing
      pneumonia not requiring hospitalization is of viral etiology, thus does not require
      antibiotic treatment. The cost of antibiotic treatment for all children with pneumonia is
      high; an estimated US$ 200 million in South Asia & sub Saharan Africa alone. Since more than
      60% of pneumonia is classified as non-severe (fast breathing), this puts a strain on already
      under-sourced programmes in low-income countries. Giving antibiotics where they confer no
      benefit also puts the child at risk of side effects and increases the risk of antimicrobial
      resistance in the community. This uncertainty forms the basis of the proposed study.
      Investigators propose to show in a clinical trial that the outcome of children diagnosed with
      WHO defined fast breathing pneumonia is similar regardless of whether they receive
      antibiotics or not. This study will be conducted in five primary health care centers located
      in low income communities of Karachi, Pakistan, with extensive trial experience. Children
      identified to have fast breathing without any danger signs will be randomized to receive
      either three days of the WHO recommended oral antibiotic (amoxicillin 250mg/5ml using WHO
      weight bands) or matching placebo (a drug that will taste and look like the amoxicillin but
      will not have an active ingredient) by a study physician working at the primary health
      center. The assignment of the antibiotic amoxicillin or placebo to a child will be done using
      a computer generated randomization list in a manner that at the end of the trial, there are
      equal numbers of children in both arms of the trial. Based on the statistical calculations
      for sample size, investigators need to assign 1214 children to receive amoxicillin and the
      same number of children to receive placebo. All children will receive the antibiotic or
      placebo under supervision of the primary health care physician in the morning. Evening doses
      will be delivered by locally hired Community Health Workers (CHWs) visiting the children at
      their home. All children will be assessed again on day 3 by a study physician to see if the
      child's presenting sign of high respiratory rate has resolved or not. All children with
      persistently high respiratory rate and/or development of a new clinical sign indicating
      illness progression will be labeled a treatment failure. There will invariably be some
      children with treatment failure in both the treatment arms; investigators hypothesize that
      there will be equal number of treatment failures in both the groups i.e. around 5%.
    

Intervention name(s): Placebo; Amoxicillin
Intervention type(s): Drug; Drug
Intervention description(s): This is an non inferiority trial, the intervention is a placebo; Amoxicillin Liquid
Intervention MeSH terms: Amoxicillin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Amoxicillin; Placebo