A randomized controlled trial of hospital versus home based therapy with oral amoxicillin for severe pneumonia in children aged 3 - 59 months: The IndiaCLEN Severe Pneumonia Oral Therapy (ISPOT) Study (original) (raw)
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The Lancet, 2008
Background WHO case management guidelines for severe pneumonia involve referral to hospital for treatment with parenteral antibiotics. If equally as eff ective as parenteral treatment, home-based oral antibiotic treatment could reduce referral, admission, and treatment costs. Our aim was to determine whether home treatment with high-dose oral amoxicillin and inpatient treatment with parenteral ampicillin were equivalent for the treatment of severe pneumonia in children. Methods This randomised, open-label equivalency trial was done at seven study sites in Pakistan. 2037 children aged 3-59 months with severe pneumonia were randomly allocated to either initial hospitalisation and parenteral ampicillin (100 mg/kg per day in four doses) for 48 h, followed by 3 days of oral amoxicillin (80-90 mg/kg per day; n=1012) or to home-based treatment for 5 days with oral amoxicillin (80-90 mg/kg per day in two doses; n=1025). Follow-up assessments were done at 1, 3, 6, and 14 days after enrolment. The primary outcome was treatment failure (clinical deterioration) by day 6. Analyses were done per protocol and by intention to treat. This trial is registered, ISRCTN95821329. Findings In the per-protocol population, 36 individuals were excluded from the hospitalised group and 37 from the ambulatory group, mainly because of protocol violations or loss to follow-up. There were 87 (8•6%) treatment failures in the hospitalised group and 77 (7•5%) in the ambulatory group (risk diff erence 1•1%; 95% CI-1•3 to 3•5) by day 6. Five (0•2%) children died within 14 days of enrolment, one in the ambulatory group and four in the hospitalised group. In each case, treatment failure was declared before death and the antibiotic had been changed. None of the deaths were considered to be associated with treatment allocation; there were no serious adverse events reported in the trial. Interpretation Home treatment with high-dose oral amoxicillin is equivalent to currently recommended hospitalisation and parenteral ampicillin for treatment of severe pneumonia without underlying complications, suggesting that WHO recommendations for treatment of severe pneumonia need to be revised.
Indian Journal of Child Health
neumonia is one of the leading causes of morbidity and mortality in children under-5 years of age in developing countries. Globally, pneumonia accounted for approximately 16% of 5.6 million under-five deaths, killing around 880,000 children in 2016 [1]. In India, 158,000 underfive children died of pneumonia in the same year accounting for nearly 18% of global burden. Bacterial infection has a far greater role as a cause of pneumonia in children, especially in developing countries. Researchers have identified Streptococcus pneumoniae and Haemophilus influenzae as the common etiological agents of pneumonia in developing countries [2]. These organisms respond to semi-synthetic penicillin [3]. The diagnosis of pneumonia is purely clinical, based on the presence of fast breathing, while chest retraction and general danger signs are used to classify the disease severity [4]. There is lack of consistency in treatment guidelines issued by various organizations. As per IMNCI and INDIACLEN task force on pneumonia, the presence of chest retractions implies severe pneumonia which has to be managed with intravenous (IV) antibiotics [4,5]. On the contrary, as per the WHO guidelines, presences of chest retractions signify non-severe pneumonia managed with oral antibiotics alone [6]. This study was a non-inferiority study, with the primary objective to compare the efficacy of oral amoxicillin against IV ampicillin in children aged 3-59 months with chest retraction pneumonia. The secondary objective was to identify the risk factors associated with the absence of clinical improvement in these children at the end of 48 h of treatment. MATERIALS AND METHODS We undertook a non-blinded randomized controlled, noninferiority trial of oral amoxicillin and IV ampicillin in children aged 3-59 months with chest retraction pneumonia, in the ABSTRACT Background: Pneumonia is one of the leading causes of under-five mortality. There is lack of consistency in treatment guidelines issued by various organizations. Objective: The primary objective of the study was to compare the efficacy of oral amoxicillin against intravenous (IV) ampicillin in children aged 3-59 months with chest retraction pneumonia. The secondary objective was to identify the risk factors associated with the absence of clinical improvement at the end of 48 h of treatment. Materials and Methods: This was a non-blinded randomized controlled, non-inferiority trial of oral amoxicillin 80 mg/kg/day in two divided doses and IV ampicillin 200 mg/kg/day in three divided doses in children aged 3-59 months with chest retraction pneumonia. The study was conducted in the pediatric wards of a tertiary care facility from November 2016 to September 2017. The children were followed up after 48 h and 5 days for the clinical improvement. The primary outcome considered was absence of improvement or deterioration in the study children at the end of 48 h of initiation of therapy and was expressed as risk difference between the two treatment groups. Multivariate regression analysis was performed to determine the predictors of poor outcome of the disease. Results: Risk difference of treatment failure between both groups was-3.7% (95% confidence interval [CI] −16.8%-9.4%). The presence of wheeze and X-ray findings of pneumonia was significant independent risk factors for poor outcome at the end of 48 h. Conclusion: Oral amoxicillin is not inferior to IV penicillin in the treatment of chest retraction pneumonia in children aged 3-59 months. The presence of wheeze and X-ray findings suggestive of pneumonia can be used as prognostic indicators in children.
Thorax, 2007
Objective: To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes. Methods: A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations ,85% in air, shock requiring .20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age ,6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be ,38˚C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness. Results: Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p,0.001 for equivalence). Three children in the oral group were changed to IV antibiotics and seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups. Conclusion: Oral amoxicillin is effective for most children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society guidelines on childhood pneumonia could not draw on evidence to address this issue. This will spare children and their families the trauma and pain of cannulation, and children will spend less time in hospital.
Archives of Disease in Childhood, 2007
Introduction: WHO pneumonia case management guidelines recommend oral amoxicillin as first line treatment for non-severe pneumonia. Increasing treatment failure rates have been reported over a period of time, which could possibly be due to increasing minimum inhibitory concentrations of Streptococcus pneumoniae and Haemophilus influenzae for amoxicillin. Microbiological data show that this resistance can be overcome by increasing amoxicillin dosage. Based on this data, we examined whether we can improve the clinical outcome in non-severe pneumonia by doubling the dose of amoxicillin. Methods: A double blind randomised controlled trial was conducted in the outpatient departments of four large hospitals in Pakistan. Children aged 2-59 months with non-severe pneumonia were randomised to receive either standard (45 mg/kg/day) or double dose (90 mg/kg/day) oral amoxicillin for 3 days and then followed up for 14 days. Final outcome was treatment failure by day 5. Results: From September 2003 to June 2004, 876 children completed the study. 437 were randomised to standard and 439 to double dose oral amoxicillin. 20 (4.5%) children in the standard and 25 (5.7%) in the double dose group had therapy failure by day 5. Including the relapses, by day 14 there were 26 (5.9%) cumulative therapy failures with standard and 35 (7.9%) with double dose amoxicillin. These differences were not statistically significant (p = 0.55 and p = 0.29, respectively). Conclusion: Clinical outcome in children aged 2-59 months with non-severe pneumonia is the same with standard and double dose oral amoxicillin. Non-severe pneumonia can be treated effectively and safely with a 3 day course of a standard dose.
Journal of Antimicrobial Chemotherapy, 2014
Oral amoxicillin (50 mg/kg/day) thrice daily is the first-line therapy for non-severe childhood pneumonia. Compliance could be enhanced if two daily doses are employed. We assessed the equivalence of oral amoxicillin (50 mg/kg/day) thrice or twice daily in those patients. Patients and methods: This randomized (1 : 1), controlled, triple-blinded investigation conducted at one centre in Brazil included children aged 2-59 months with non-severe pneumonia diagnosed by trained paediatricians based on respiratory complaints and radiographic pulmonary infiltrate/consolidation. Participants were randomly assigned to receive one bottle (Amoxicillin 1) at 6 am, 2 pm and 10 pm and the other bottle (Amoxicillin 2) at 8 am and 8 pm: one bottle contained amoxicillin and the other placebo and vice versa. Only the pharmacist knew patients' allocation. Follow-up assessments were done at 2, 5 and 14 days after enrolment. Chest radiographs were read by three independent radiologists. Primary outcome was treatment failure (development of danger signs, persistence of fever, tachypnoea, development of serious adverse reactions, death and withdrawal from the trial) at 48 h. ClinicalTrials.gov: identifier NCT01200706. Results: Four hundred and twelve and 408 participants received amoxicillin thrice or twice daily, respectively. Treatment failure was detected in 94 (22.8%) and 94 (23.0%) patients in intention-to-treat analysis (risk difference 0.2%; 95% CI: 25.5%-6.0%) and in 80 (20.1%) and 85 (21.3%) patients in per-protocol analysis (risk difference 1.2%; 95% CI: 24.4%-6.8%). Pneumonia was radiologically confirmed by concordant reading in 277 (33.8%) cases, among whom treatment failure was registered in 25/133 (18.8%) and 27/144 (18.8%) participants from the thrice and twice daily doses subgroups, respectively (risk difference 20.05%; 95% CI: 29.3%-9.2%). Conclusions: Oral amoxicillin (50 mg/kg/day) twice daily is as efficacious as thrice daily.
International Journal of Paediatrics and Geriatrics
Introduction: The most significant and striking feature of pneumonia is consolidation. Pneumonia continues to be the biggest killer disease globally, of less than five year's children. Pneumonia accounts for 15% of all deaths of children under 5 years old, killing 8, 08694 children in 2017. Methodology: Hospital based prospective observational comparative study. This study was conducted in the department of paediatrics, RVM institute of medical sciences and research canter. This study was approved by the RVM institutional ethical committee prior to the study. The study was conducted between the months of September 2019 to January 2020.100 children who are diagnosed with severe pneumonia were included in this the study. Results: A total of 100 children have been enrolled in the present study. Among them 56 (56%) are Males and 44 (44%) are Females. Male: female ratio was 1.3: 0.8. Treatment Failure rate in oral amoxicillin group is 24% and in Inj.ampicillin plus Amikacin (parenteral) group is 16%.The difference in treatment outcome in the two groups is not statistically significant. (p = 1.0000, p = 0.3173). Conclusion: Proper training of care givers and treating clinicians to promptly recognize the danger signs of very severe pneumonia, one can safely treat the patients with severe pneumonia with oral Amoxicillin.