Treatment of fast breathing in neonates and young infants with oral amoxicillin compared with penicillin-gentamicin combination: study protocol for a randomized, open-label equivalence trial

AFRIcan NEonatal Sepsis Trial Group, Antoinette Tshefu, Adrien Lokangaka, Cyril Engmann, Fabian Esamai, Peter Gisore, Adejumoke Idowu Ayede, Adegoke Gbadegesin Falade, Ebunoluwa A Adejuyigbe, Henry Anyabolu, Robinson D Wammanda, William N Ogala, Lu Gram, Simon Cousens, Rajiv Bahl, Nigel Rollins, Sachiyo Yoshida, Shamim Ahmed Qazi, AFRIcan NEonatal Sepsis Trial Group, Antoinette Tshefu, Adrien Lokangaka, Cyril Engmann, Fabian Esamai, Peter Gisore, Adejumoke Idowu Ayede, Adegoke Gbadegesin Falade, Ebunoluwa A Adejuyigbe, Henry Anyabolu, Robinson D Wammanda, William N Ogala, Lu Gram, Simon Cousens, Rajiv Bahl, Nigel Rollins, Sachiyo Yoshida, Shamim Ahmed Qazi

Abstract

Background: The World Health Organization recommends hospitalization and injectable antibiotic treatment for young infants (0-59 days old), who present with signs of possible serious bacterial infection. Fast breathing alone is not associated with a high mortality risk for young infants and has been treated with oral antibiotics in some settings. This trial was designed to examine the safety and efficacy of oral amoxicillin for young infants with fast breathing compared with that of an injectable penicillin-gentamicin combination. The study is currently being conducted in the Democratic Republic of Congo, Kenya and Nigeria.

Methods/design: This is a randomized, open-label equivalence trial. All births in the community are visited at home by trained community health workers to identify sick infants who are then referred to a trial study nurse for assessment. The primary outcome is treatment failure by day 8 after enrollment, defined as clinical deterioration, development of a serious adverse event including death, persistence of fast breathing by day 4 or recurrence up to day 8. Secondary outcomes include adherence to study therapy, relapse, death between days 9 and 15 and adverse effects associated with the study drugs. Study outcomes are assessed on days 4, 8, 11 and 15 after randomization by an independent outcome assessor who is blinded to the treatment being given.

Discussion: The results of this study will help inform the development of policies for the treatment of fast breathing among neonates and young infants in resource-limited settings.

Figures

FIGURE 1.
FIGURE 1.
Overall study approach.

References

    1. Liu L, Johnson HL, Cousens S, et al. Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: An updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012;379:2151–2161.
    1. World Health Organization and UNICEF. Integrated Management of Childhood Illness (IMCI) Chart Booklet. Geneva, Switzerland: World Health Organization; 2008.
    1. World Health Organization. Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Illnesses With Limited Resources. 2nd edition. Geneva, Switzerland: World Health Organization; 2013.
    1. Darmstadt GL, Baqui AH, Choi Y, et al. Bangladesh Projahnmo-2 (Mirzapur) Study Group. Validation of community health workers’ assessment of neonatal illness in rural Bangladesh. Bull World Health Organ. 2009;87:12–19.
    1. Baqui AH, El-Arifeen S, Darmstadt GL, et al. Projahnmo Study Group. Effect of community-based newborn-care intervention package implemented through two service-delivery strategies in Sylhet district, Bangladesh: A cluster-randomised controlled trial. Lancet. 2008;371:1936–1944.
    1. Bhandari N, Bahl R, Bhatnagar V, et al. Treating sick young infants in urban slum setting [letter]. Lancet. 1996;347:1774–1775.
    1. Zaidi AK, Tikmani SS, Warraich HJ, et al. Community-based treatment of serious bacterial infections in newborns and young infants: A randomized controlled trial assessing three antibiotic regimens. Pediatr Infect Dis J. 2012;31:667–672.
    1. Young Infant Clinical Signs Study Group. Clinical signs that predict severe illness in children under age 2 months: A multicentre study. Lancet. 2008;371:135–142.
    1. Reddy MH, Bang AT. How to identify neonates at risk of death in rural India: Clinical criteria for the risk approach. J Perinatol. 2005;25(suppl 1):S44–S50.
    1. Bang AT, Bang RA, Reddy MH, et al. Simple clinical criteria to identify sepsis or pneumonia in neonates in the community needing treatment or referral. Pediatr Infect Dis J. 2005;24:335–341.
    1. Baqui AH, Arifeen SE, Williams EK, et al. Effectiveness of home-based management of newborn infections by community health workers in rural Bangladesh. Pediatr Infect Dis J. 2009;28:304–310.
    1. Bang AT, Bang RA, Morankar VP, et al. Pneumonia in neonates: Can it be managed in the community? Arch Dis Child. 1993;68(5 Spec No):550–556.
    1. Sazawal S, Black RE Pneumonia Case Management Trials Group. Effect of pneumonia case management on mortality in neonates, infants and preschool children: A meta-analysis of community-based trials. Lancet Infect Dis. 2003;3:547–556.
    1. Theodoratou E, Al-Jilaihawi S, Woodward F, et al. The effect of case management on childhood pneumonia mortality in developing countries. Int J Epidemiol. 2010;39(suppl 1):i155–i171.
    1. AFRINEST (AFRIcan NEonatal Sepsis Trial) Group. Simplified regimens for management of neonates and young infants with severe infection in situations when hospital admission is not possible: Study protocol for a randomized, open-label equivalence trial. Pediatr Infect Dis J. 2013;32(suppl):S26–S32.
    1. Zaidi AKM, Baqui AH, Qazi SA, et al. Scientific rationale for study design of community-based simplified antibiotic therapy trials in newborns and young infants with clinically diagnosed severe infections in South Asia and sub-Saharan Africa. Pediatr Infect Dis J. 2013;32(suppl):S7–S11.
    1. Kabra SK, Lodha R, Pandey RM. Antibiotics for community-acquired pneumonia in children. Cochrane Database Syst Rev. 2010:CD004874.
    1. Grant GB, Campbell H, Dowell SF, et al. World Health Organization Department of Child and Adolescent Health and Development. Recommendations for treatment of childhood non-severe pneumonia. Lancet Infect Dis. 2009;9:185–196.
    1. Atkinson M, Lakhanpaul M, Smyth A, et al. A multicentre randomised controlled equivalence trial comparing oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children PIVOT Trial. Thorax. 2007;62:1102–1106.
    1. Addo-Yobo E, Chisaka N, Hassan M, et al. Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: A randomised multicentre equivalency study. Lancet. 2004;364:1141–1148.
    1. Hazir T, Fox LM, Nisar YB, et al. New Outpatient Short-Course Home Oral Therapy for Severe Pneumonia Study Group. Ambulatory short-course high-dose oral amoxicillin for treatment of severe pneumonia in children: A randomised equivalency trial. Lancet. 2008;371:49–56.
    1. Addo-Yobo E, Anh DD, El-Sayed HF, et al. Multicenter Amoxicillin Severe pneumonia Study (MASS) Group. Outpatient treatment of children with severe pneumonia with oral amoxicillin in four countries: The MASS study. Trop Med Int Health. 2011;16:995–1006.
    1. Scott JA, Brooks WA, Peiris JS, et al. Pneumonia research to reduce childhood mortality in the developing world. J Clin Invest. 2008;118:1291–1300.
    1. Bang AT, Bang RA, Stoll BJ, et al. Is home-based diagnosis and treatment of neonatal sepsis feasible and effective? Seven years of intervention in the Gadchiroli field trial (1996 to 2003). J Perinatol. 2005;25(suppl 1):S62–S71.
    1. Wall SN, Mazzeo CI, Adejuyigbe EA, et al. Ensuring quality in the AFRINEST and SATT trials. Pediatr Infect Dis J. 2013;32(suppl):S39–S45.
    1. Bahl R, Martines J, Ali N, et al. Research priorities to reduce global mortality from newborn infections by 2015. Pediatr Infect Dis J. 2009;28(1 suppl):S43–S48.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere