Randomized Trial of Amoxicillin Versus Placebo for (Fast Breathing) Pneumonia
Information source: Aga Khan University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pneumonia; Tachypnea
Intervention: Placebo (Drug); Amoxicillin (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Aga Khan University Official(s) and/or principal investigator(s): Fyezah Jehan, Msc, Principal Investigator, Affiliation: Aga Khan Univeristy
Overall contact: Fyezah Jehan, MSc, Phone: +922134864955, Email: fyezah.jehan@aku.edu
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.
Clinical Details
Official title: A Double Blind Community-based Randomized Trial of Amoxicillin Versus Placebo for Fast Breathing Pneumonia in Children Aged 2-59 Months in Karachi, Pakistan
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Cumulative Treatment failure
Secondary outcome: Relapse
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%.
Eligibility
Minimum age: 2 Months.
Maximum age: 59 Months.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- History of cough or difficult breathing < 14 days (observed or reported) AND
- Respiratory rate ≥ 50 breaths per minute in children 2 to <12 months (on two
consecutive readings by independent physicians) OR respiratory rate ≥ 40 breaths per
minute in children12- 59 months (on two consecutive readings by independent
physicians) AND
- Written informed consent by a legal guardian
Exclusion Criteria:
- Previously enrolled in study
- Pedal edema
- History of hospitalization in last two weeks
- With severe lower chest wall in-drawing
- Known asthmatics,TB or other severe illness
- Antibiotics taken in last 48 hours
- Bulging fontanel
- Congenital heart disease
- Any surgical condition requiring hospitalization
- Out of catchment area
- Any general danger sign as defined by WHO: Stridor when calm; hypoxia (SaO2 <
90% in air) ; inability to feed; persistent vomiting (after three attempts to feed
the baby within ½ hour); convulsions; reduced conscious level
Locations and Contacts
Fyezah Jehan, MSc, Phone: +922134864955, Email: fyezah.jehan@aku.edu
PHC Ali Akber Shah, Karachi, Sind, Pakistan; Recruiting Fyezah Jehan, Msc
PHC at Ibrahim Haidry Goth, Karachi, Sind, Pakistan; Recruiting Fyezah Jehan, Msc
Additional Information
Starting date: September 2014
Last updated: April 29, 2015
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