Community Based Management of Fast Breathing in Infants Aged < 60 Days in Low-income Settlements of Karachi

Study Overview
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Brief Summary
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The aim of the study is to determine optimal management of isolated fast breathing in young infants in a trial design conducted in primary care settings. The investigators hypothesized that proportion of infants who fail therapy will be 4% in each group. A 6% or less difference in failure rate will be considered equivalent.

Detailed Description
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The management of isolated fast breathing is therefore unknown and our experience suggests that these infants could perhaps be managed without antibiotics. Widespread application of the WHO clinical algorithm could therefore result in the referral of as many as 13.7% (135.7 per 1000 live births) of all infants for isolated fast breathing, the vast majority of these unnecessarily, and exposing infants to a high risk of nosocomial sepsis and hospital mortality in addition to over-burdening health resources.

Official Title
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Community Based Management of Fast Breathing in Infants Aged < 60 Days: A Double-Blind, Randomized Placebo-Controlled Trial in Low-income Settlements of Karachi

Conditions
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Fast Breathing in Young Infants

Intervention / Treatment
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* Drug: Amoxicillin
* Drug: Sugar Syrup


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Young infant (0-59 days of age) Fast breathing i.e., respiratory rate ≥60 breaths/min O2 Saturation ≥90% Resident of catchment area (to ensure complaint and follow up) Refused hospitalization and investigations Informed consent is provided by a parent (or legal guardian). Exclusion Criteria: Preterm infants (born <37 weeks) Presence of audible murmur Any concurrent signs of severe infection: not feeding well movement only when stimulated severe chest in-drawing axillary temperature ≥38.0oC or ≤35.5oC Any sign of being critically ill (Cyanosis, bulging fontanel, unable to feed, unable to cry, apnoea, convulsions, unconscious, persistent vomiting) Weight <1800gm at the time of presentation Major congenital malformations or suspected chromosomal abnormalities Hospitalization for illness in the last two weeks Previous inclusion in the study

Ages Eligible for Study
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Maximum Age: 59 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amoxicillin<br>This is an active intervention | Drug: Amoxicillin<br>* 80-100 mg/kg/day in 2 divided doses for 7 days For convenience dose divided into six weight bands Table 2: Dose of amoxicillin Weight band Amount per dose Daily dose Lower Limit (mg or units /kg/d) Upper Limit (mg or units /kg/d) Amoxicillin - desired range 75-100 mg/kg/day (25mg/ml (125mg/5ml); twice daily orally)* 1.8-1.9 kg 3.0 ml 150 mg 75.4 100.0 2.0-2.4 kg 4.0 ml 200 mg 80.3 100.0 2.5-2.9 kg 5.0 ml 250 mg 83.6 100.0 3.0-3.9 kg 6.0 ml 300 mg 75.2 100.0 4.0-4.9 kg 8.0 ml 400 mg 80.2 100.0 5.0-5.9 kg 10.0 ml 500 mg 83.5 100.0<br>|
| Placebo Comparator: Sugar Syrup<br> | Drug: Sugar Syrup<br>* It will be given 2 times/day for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure | O2 sat <90% on Day 2 or any time until Day 7. Clinical deterioration: emergence of any sign of being critically ill or severe infection at any time after randomization (as defined in exclusion criteria) Development of serious adverse effect of the study antibiotics (death, organ failure, anaphylactic reaction, severe diarrhoea, disseminated and severe rash). Hospitalization any time after admission in the study. Death anytime within day 1-7 of enrolment | Day 8 of enrollemnt | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance to treatment | To label as per protocol infant should receive 100% (4 doses) of doses in first 2 days followed by 70% (7 doses) of doses from day 3 to day 8. | 80% of total dosage | 
| Proportion of infants relapse |  | No treatment failure by day 8 and signs of sepsis or fast breathing between day 8-14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fast breathing, Young infants, Management, Amoxicillin, Placebo