None listed
Conditions
Brief summary
Objective: To conduct a multi-centre randomized controlled trial in three countries in Africa (Democratic Republic of Congo, Kenya and Nigeria) to test the safety and efficacy of simplified antibiotic regimens for treating possible serious bacterial infection in 0-59 day-old infants Participants: Study participants will be young infants 0 to 59 days old, from settings in low- and middle-income countries with a high infant mortality (at least 60/1000 live births), with clinical signs of possible serious bacterial infection whose families do not accept or cannot access referral level care. Infants who are critically ill will be excluded, and the study participants will be stratified into two groups according to the severity of the possible serious bacterial infection on admission: - severe infection: not feeding well, movement only when stimulated, severe chest in-drawing, axillary temperature >38.0 degree Centigrade or <35.5 degree Centigrade; and - fast breathing alone: respiratory rate 60 or more per minute. The study will enroll a total of 6,200 young infants -- 3,600 in the stratum of young infants with possible severe infection and 2,600 in the stratum of less severe infection. Reference treatment (Comparison): The comparison group will receive injection gentamicin once daily and injection procaine penicillin once daily for 7 days (Treatment Regimen A, 14 injections in total). Experimental treatments (Intervention): The treatment regimens under evaluation will be: 1. For severe infection: Treatment Regimen B: injection gentamicin once daily and oral amoxicillin twice daily for 7 days (7 injections in total); Treatment Regimen C: injection gentamicin once daily and injection procaine penicillin once daily for 2 days, thereafter oral amoxicillin for 5 days (4 injections in total) Treatment Regimen D: injection gentamicin once daily and oral amoxicillin twice daily for 2 days, thereafter oral amoxicillin twice daily for 5 days (2 injections in total) 2. Fast breathing alone: Treatment Regimen E: oral amoxicillin twice daily for 7 days Outcomes: Treatment failure in the first week following initiation of treatment (primary outcome); death in the first week following initiation of treatment, death the week following completion of treatment, relapse in the week following completion of treatment, and severe adverse effects related to the antibiotics (secondary outcomes).
Interventions
Stratum I (severe infection)
To test the efficacy of the following three simpler regimens, compared to the reference regimen, in children who have 'severe infection'
- Treatment regimen B: injection gentamicin once daily (4-6.5 mg/kg/day) and oral amoxicillin (75-100 mg/kg/day) twice daily for 7 days (7 injections in total)
- Treatment regimen C: injection gentamicin (4-6.5 mg/kg/day) once daily and injection procaine penicillin (40,000-60,000 units/kg/day) once daily for 2 days, thereafter ora
Stratum I (severe infection) To test the efficacy of the following three simpler regimens, compared to the reference regimen, in children who have 'severe infection' - Treatment regimen B: injection gentamicin once daily (4-6.5 mg/kg/day) and oral amoxicillin (75-100 mg/kg/day) twice daily for 7 days (7 injections in total) - Treatment regimen C: injection gentamicin (4-6.5 mg/kg/day) once daily and injection procaine penicillin (40,000-60,000 units/kg/day) once daily for 2 days, thereafter oral amoxicillin (75-100 mg/kg/day) for 5 days (4 injections in total) - Treatment regimen D: injection gentamicin (4-6.5 mg/kg/day) once daily and oral amoxicillin (75-100 mg/kg/day) for 5 days twice daily for 2 days, thereafter oral amoxicillin (75-100 mg/kg/day) twice daily for 5 days (2 injections in total) Stratum II (fast breathing only) To test the efficacy of the following simpler regimen, compared to the reference regimen, in children who have fast breathing: - Treatment regimen E: Oral amoxicillin (75-100 mg/kg/day) twice daily for 7 days
Sponsors
World Health Organization
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
1 Days to 59 Days
Healthy volunteers
No
Inclusion criteria
Stratum 1 (severe infection): One or more of the following five signs of 'severe infection' - not feeding well, movement only when stimulated, severe chest indrawing, axillary temperature >38.0 degree Centigrade or <35.5 degree Centigrade and informed consent is provided by a parent (or legal guardian). Stratum II (fast breathing only): Fast breathing i.e., respiratory rate 60 or more per minute and Informed consent is provided by a parent (or legal guardian)
Exclusion criteria
Stratum I: Exclusion Criteria - Critically ill infant characterized by presence of any of the following signs - unconscious, convulsions, unable to feed at all, apnea, unable to cry, cyanosis, bulging fontanelle, major congenital malformations inhibiting oral antibiotic intake, active bleeding requiring transfusion, surgical conditions needing hospital referral, persistent vomiting defined as vomiting following three attempts to feed the baby within ½ hour - Very low weight (<1500g at the time of presentation) - Hospitalization for illness in the last two weeks - Previous inclusion in the study Stratum II: Exclusion Criteria - Any signs of severe infection: not feeding well, movement only when stimulated, severe chest in-drawing, axillary temperature >38.0 degree Centigrade or <35.5 degree Centigrade , - Any sign of being critically ill - Very low weight (<1500g at the time of presentation) - Hospitalization for illness in the last two weeks - Previous inclusion in the study
Outcome results
None listed