title: Ambulatory Treatment of Fast Breathing in Young Infants Aged <60 Days: A Double-Blind, Randomized, Placebo-Controlled Equivalence Trial in Low-Income Settlements of Karachi.
abstract: (See the Editorial Commentary by Jehan and Qazi on pages 190-1) BACKGROUND: Integrated Management of Childhood Illness recommends that young infants with isolated fast breathing be referred to a hospital for antibiotic treatment, which is often impractical in resource-limited settings. Additionally, antibiotics may be unnecessary for physiologic tachypnea in otherwise well newborns. We tested the hypothesis that ambulatory treatment with oral amoxicillin for 7 days was equivalent (similarity margin of 3%) to placebo in young infants with isolated fast breathing in primary care settings where hospital referral is often unfeasible.
  
  
  METHODS
  This randomized equivalence trial was conducted in 4 primary health centers of Karachi, Pakistan. Infants presenting with isolated fast breathing and oxygen saturation ≥90% were randomly assigned to receive either oral amoxicillin or placebo twice daily for 7 days. Enrolled infants were followed on days 1-8, 11, and 14. The primary outcome was treatment failure by day 8, analyzed per protocol. The trial was stopped by the data safety monitoring board due to higher treatment failure rate and the occurrence of 2 deaths in the placebo arm in an interim analysis.
  
  
  RESULTS
  Four hundred twenty-three infants fulfilled per protocol criteria in the amoxicillin arm and 426 in the placebo arm. Twelve infants (2.8%) had treatment failure in the amoxicillin arm and 25 (5.9%) in the placebo arm (risk difference, 3.1; P value .04). Two infants in the placebo arm died, whereas no deaths occurred in the amoxicillin arm. Other adverse outcomes, as well as the proportions of relapse, were evenly distributed across both study arms.
  
  
  CONCLUSIONS
  This trial failed to show equivalence of placebo to amoxicillin in the management of isolated fast breathing without hypoxemia or other clinical signs of illness in term young infants.
  
  
  BACKGROUND
  NCT01533818.
authors.affiliation: Departments of Paediatrics and Child Health, shiyam.sunder@aku.edu.
authors.forename: Shiyam S
authors.initials: SS
authors.lastname: Tikmani
authors.affiliation: Departments of Paediatrics and Child Health.
authors.forename: Amber A
authors.initials: AA
authors.lastname: Muhammad
authors.affiliation: Departments of Paediatrics and Child Health.
authors.forename: Yasir
authors.initials: Y
authors.lastname: Shafiq
authors.affiliation: Departments of Paediatrics and Child Health.
authors.forename: Saima
authors.initials: S
authors.lastname: Shah
authors.affiliation: Departments of Paediatrics and Child Health.
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Departments of Paediatrics and Child Health.
authors.forename: Imran
authors.initials: I
authors.lastname: Ahmed
authors.affiliation: Community Health Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Azam
authors.affiliation: Community Health Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Omrana
authors.initials: O
authors.lastname: Pasha
authors.affiliation: Departments of Paediatrics and Child Health.
authors.forename: Anita K M
authors.initials: AK
authors.lastname: Zaidi
mesh_terms: D000553:Ambulatory Care / Q000379:methods; D000658:Amoxicillin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010154:Pakistan; D011203:Poverty; D012720:Severity of Illness Index; D059245:Transient Tachypnea of the Newborn / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000658:Amoxicillin
keywords: amoxicillin; clinical trial.; fast breathing; newborn; young infants