Official Title: “Randomized Controlled Trial of Intramuscular Ceftriaxone Versus Procaine Penicillin Versus Cotrimoxazole and Gentamicin for Management of Serious Bacterial Infections in Young Infants in Community Settings”

Approximately one-third of neonatal deaths in developing countries are due to infections acquired through the birth canal and/or exposure to an unclean environment soon after birth.

Current World Health Organization recommendations for the management of infants younger than 2 months of age who have serious bacterial infections involve hospitalization and parenteral therapy for at least 10 days with antibiotic regimens containing penicillin or ampicillin combined with an aminoglycoside.However, in many settings throughout the developing world, this is not currently possible, nor is this standard of care likely to be feasible in the near future. Several studies have reported that for a variety of sociocultural reasons many families are unable or unwilling to access hospital-based care and their sick young infants do not get hospitalized, and instead, receive a variety of home-based antibiotic therapies, or none at all. In our community field sites, approximately 70% of families refuse hospital referral for a sick newborn, despite provision of transport.

Thus, there is an urgent need to define the role of community/first-level facility-based care versus hospitalization for the management of young infants with serious bacterial infections, and the potential for community-based parenteral antibiotics as an alternative strategy in resource poor areas with high neonatal mortality rates. Bang and colleagues have demonstrated significant reductions in neonatal mortality from infections in an underdeveloped rural district in Maharashtra, India by a field-based case management approach which used oral cotrimoxazole and intramuscular gentamicin given for 7 days as treatment for neonates with sepsis.

This study is an equivalence randomized controlled trial (RCT) comparing once daily IM ceftriaxone injection to once daily IM procaine penicillin and gentamicin injection, to once daily intramuscular gentamicin injection and twice daily oral cotrimoxazole, given for 7 days in babies with clinically-diagnosed possible serious bacterial infection (pneumonia, or sepsis with or without local infections such as skin or umbilical infections) whose families refused referral to a hospital. After supplementary informed consent, patients meeting specific inclusion and exclusion criteria are randomly allocated to one of the three regimens being tested. The study hypothesis is that all 3 regimens will perform equally well in the treatment of sepsis in a first-level facility setting.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment

Intervention(s) in this Clinical Trial

• Drug: ceftriaxone, procaine penicillin and gentamicin, oral cotrimoxazole and gentamicin

Primary Measures

• The primary outcome of success rate will be defined as patient cured or improved with the regimen assigned to, on day 7 of therapy.

Secondary Measures

• Completion rates
• Adverse events
• Relapse rates

Inclusion Criteria:

• Age 0-59 days presenting to Young Infant community study site
• Clinical diagnosis of possible serious bacterial infection by study physician according to specified clinical criteria
• Parents refuse to accept referral care and sign (or thumb imprint) document stating this.
• Parents consent to community centre-based intramuscular antibiotic injections

Exclusion Criteria:

• Age over 59 days
• Presence of severe jaundice diagnosed clinically or by laboratory investigation (bilirubin > 12 g/dl in term and > 7 in pre-term baby).
• Presence of obvious meningitis (bulging fontanelle, observed seizures)
• Patient previously enrolled in antibiotic therapy trial
• Parents accept hospital referral
• Parents do not consent to any injectable therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 59 Days

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Aga Khan University

Overall Clinical Trial Officials and Contacts

Anita KM Zaidi, MBBS, SM Principal Investigator Department of Pediatrics, Aga Khan University  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00189384

Study ID Number: SC/SNL 11150-0902-50001-269

ClinicalTrials.gov Identifier: NCT00189384

Health Authority: Pakistan:Pakistan Medical Research Council