Randomized Trial of Amoxicillin Versus Placebo for (Fast Breathing) Pneumonia

NCT02372461 | Completed DMC

• 2 other identifiers: MR/L004283/1OPP1158281
• Study Type: interventional
• Target: 4,000
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pneumonia; Tachypnea

Keywords

Amoxicillin; Placebo

Outcome Measures

Primary Outcomes (1)

• Cumulative Treatment failure

  Primary outcome will be cumulative treatment failure at or before 3 days. The following definitions will be used: either death, any danger sign, onset of chest in drawing as defined by WHO, hospitalization due to any reason, change in antibiotic regimen by study physician for new-onset infectious co-morbidity or change in antibiotic regimen by study physician for serious non-fatal antibiotic-associated adverse event on or before day 3.

  Day 0-3

Secondary Outcomes (1)

• Relapse

  Day 4-14

Study Arms (2)

Experimental

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Control

ACTIVE COMPARATOR

Amoxicillin Liquid

Drug: Amoxicillin

Interventions

Placebo DRUG

This is an non inferiority trial, the intervention is a placebo

Experimental

Amoxicillin DRUG

Amoxicillin Liquid

Control

Eligibility Criteria

• Age: 2 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aga Khan University: lead

Study Sites (1)

PHC at Ibrahim Haidry Goth, Ali Akber Shah Colony, Rerhi Goth, Bhains Colony

Karachi, Sindh, Pakistan

Location

Related Publications (3)

• Jehan F, Nisar I, Kerai S, Balouch B, Brown N, Rahman N, Rizvi A, Shafiq Y, Zaidi AKM. Randomized Trial of Amoxicillin for Pneumonia in Pakistan. N Engl J Med. 2020 Jul 2;383(1):24-34. doi: 10.1056/NEJMoa1911998.

  PMID: 32609980 DERIVED

• Brown N, Rizvi A, Kerai S, Nisar MI, Rahman N, Baloch B, Jehan F. Recurrence of WHO-defined fast breathing pneumonia among infants, its occurrence and predictors in Pakistan: a nested case-control analysis. BMJ Open. 2020 Jan 7;10(1):e035277. doi: 10.1136/bmjopen-2019-035277.

  PMID: 31915178 DERIVED

• Jehan F, Nisar MI, Kerai S, Brown N, Balouch B, Hyder Z, Ambler G, Ginsburg AS, Zaidi AK. A double blind community-based randomized trial of amoxicillin versus placebo for fast breathing pneumonia in children aged 2-59 months in Karachi, Pakistan (RETAPP). BMC Infect Dis. 2016 Jan 13;16:13. doi: 10.1186/s12879-015-1334-9.

  PMID: 26758747 DERIVED

MeSH Terms

Conditions

Pneumonia; Tachypnea

Interventions

Amoxicillin

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Fyezah Jehan, Msc

  Aga Khan Univeristy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: February 26, 2015
• Study Start: November 9, 2014
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: September 16, 2019

Record last verified: 2019-09

Locations

PA (1)