Projects

IndiaCLEN Multicentre Trial of Home versus Hospital Oral Amoxicillin for Management of Severe Pneumonia in Children (ISPOT)
 Background:

In an effort to address the high rate of mortality due to acute respiratory infection (ARI) among children under five years of age, the WHO launched a program to improve the management of ARI. The main objectives of the program were to reduce child mortality due to ARI and to rationalize antibiotic use by using a standard case management strategy. The program recommendations include: hospitalization and parenteral antibiotics. Other supportive therapy is also recommended for those children who also have lower chest indrawing (considered to be a sign of severe pneumonia) but who otherwise are accepting treatment orally and for those with features of very severe illness such as lethargy, convulsions, cyanosis, grunt, inability to feed (considered to be signs of very severe pneumonia). For severe pneumonia (pneumonia and lower chest indrawing) the program recommends either injectable benzyl penicillin or ampicillin every 6 hours for at least 3 days. After the child has improved, it is recommended to switch to oral ampicillin, amoxicillin or daily procaine penicillin injections and to complete a 5-day course of antibiotics. The questions raised by researchers and clinicians regarding these WHO guidelines are as follows:

  • Should the children with severe pneumonia be given injectable antibiotics at all and if the antibiotics are given should they be given orally to children with severe pneumonia?

  • Should treatment be administered at the hospital or in the home?

Two important studies emerged from these research questions the Amoxicillin Penicillin Pneumonia International study (APPIS) and New Outpatient Short-course Home Oral Therapy for Severe Pneumonia (NO SHOTS) study. The APPIS study was a large, multicenter, randomized, controlled trial which compared injectable penicillin versus oral amoxicillin was conducted at tertiary care centers in 8 countries. The study found that injectable penicillin and oral amoxicillin were equivalent in the treatment of severe pneumonia in hospitalized children aged 3-59 months. The NO SHOTS study was conducted in Pakistan and showed that home treatment with high-dose oral amoxicillin was equivalent to currently recommended hospitalization and parenteral ampicillin for treatment of severe pneumonia without complications. The evidence generated by these two studies strongly suggested that the WHO recommendations for treatment of severe pneumonia be revisited.

Currently, the national program, Reproductive Child Health II implements the Integrated Management of Neonatal and Childhood Illness (IMNCI) for management of pneumonia in children under five. The national program is based on the WHO ARI management guidelines. Based on the findings in the APPIS and NO-SHOTS studies, the RCH II guidelines may require modification. Currently, the approach used in India by community health centers and by private health practitioners is to administer parenteral antibiotics to children with pneumonia. This study intends to show that home treatment of severe pneumonia in children with oral antibiotics is equivalent to the same treatment of oral antibiotics that is currently being provided in hospitals.

 Objectives:

Primary objectives

  • To assess the rates of treatment failure within the first 7 days and the efficacy of a 7-day course of oral amoxicillin when administered at home in comparison to administration of oral amoxicillin within the first 48 hours in the hospital

Secondary objectives

  • To determine the proportion of children who need to restart antibiotics i.e. “failure of treatment”, between day 8 and 14 due to reappearance of any danger signs, lower chest indrawing or fast breathing which is non-responsive to three trials of nebulization with bronchodilator
  • To identify clinical predictors at baseline and during the course of treatment that predicts “failure of oral treatment”, from enrollment until day 14
  • To determine the costs of home and hospital management of severe pneumonia with oral amoxicillin
  • To determine in children receiving oral amoxicillin for severe pneumonia those that left against medical advice or voluntary withdrawal of consent from day 7 to day 14
  • To determine in children receiving oral amoxicillin for severe pneumonia those who were lost to follow-up from day 8 to day 14
 Methodology:

This study is an open-labeled, multi-centered, randomized clinical trial to determine the differences in the failure of treatment of children (3 to 59 months) with severe pneumonia with a 7-day course of oral amoxicillin administered during the first 48 hours in the hospital in comparison to children who were sent home to receive the same treatment after enrollment in the study. Children (3-59 months) who present to the outpatient department of a participating community health center with a history of cough or difficult breathing and are found to have lower chest indrawing will be referred to a member of the investigation team. That team member will perform the screening and determine the eligibility for the trial.

 Time Line:
  • Selection of research agency (Before October 1, 2010)
  • Tool development (October 2010)
  • Field work (January to June 2010)
  • Study coordination (October to May 2010)
  • Data Safety Monitoring Board (April 2010)
  • Data analysis and key findings
  • Report writing
  • Dissemination of findings
 Geographical Focus:

Chennai, Nagpur, and Chandigarh

 Key Stakeholders:
  • Government of India
  • WHO
  • UNICEF
 Expected Outcome / Output:

Based on the APPIS and NO-SHOTS studies it is estimated that children with severe pneumonia can be treated at home just as successfully as children who are treated in a hospital for 48 hours. It is expected that at least 85% of the children will respond positively to the oral antibiotics. It is also expected that the failure rate of those children treated with oral amoxicillin at home would not be different from those treated with oral amoxicillin at a hospital with at least 48 hours of supervision.