Simplified Antibiotic Therapy for Sepsis in Young Infants

Official Title: “Simplified Antibiotic Regimens for the Management of Sepsis in Young Infants in First-level Facilities: Randomized Controlled Trial”

This trial evaluates primary care clinic-based simplified antibiotic therapy options for young infants, 0-59 days old in high neonatal mortality settings in peri-urban Karachi where hospital referral is frequently refused by families.

Primary Objective

To evaluate if out-patient (clinic-based) therapy of young infants with possible serious bacterial infection with 7 days of intramuscular procaine penicillin and gentamicin (reference therapy) is equivalent to: - (1) injectable gentamicin once daily and oral amoxicillin twice daily for seven days; - (2) injectable penicillin and gentamicin once daily for two days followed by oral amoxicillin twice daily for five days; and

Hypothesis

The proportion of babies who fail therapy at (or before 7) days will be 10% in each group. A 5% or less difference in failure rates will be considered equivalent.

Study Design

This will be a randomized, three arm, open-label equivalence trial among young infants, 0-59 days of age who are diagnosed as having possible serious bacterial infection in one of the Karachi field clinics, and whose families refuse facilitated hospital referral, and the infants meet other specified inclusion criteria.

Eligible young infants will be recruited from among those referred to the clinics by trained community health workers as having clinical signs predictive of possible serious illness during regular home visits in the surveillance area, or those presenting directly to the clinics from the areas under pregnancy and newborn surveillance. A diagnosis of possible sepsis will be made by clinicians if specified clinical criteria are met.

Intervention(s) in this Clinical Trial

• Drug: procaine penicillin and gentamicin
  • procaine penicillin 50,000 units/kg by intramuscular injection once daily for 7 days; gentamicin, 5 mg/kg once daily by intramuscular injection for 7 days
• Drug: amoxicillin and gentamicin
  • oral amoxicillin 80-90 mg/kg divided in two doses for 7 days intramuscular gentamicin, 5 mg/kg once daily for 7 days
• Drug: procaine penicillin, gentamicin, amoxicillin
  • procaine penicillin, 50,000 IU/kg once daily intramuscular injection plus gentamicin 5 mg/kg once daily intramuscular injection for 2 days, followed by 5 days of oral amoxicillin, 80-90 mg/kg divided in two doses.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: procaine penicillin and gentamicin
  • Procaine penicillin, 50,000 IU/kg by intramuscular injection plus gentamicin, 5 mg/kg intramuscular injection, both given once daily for 7 days
• Experimental: Amoxicillin and gentamicin
  • Oral amoxicillin (80-90 mg/kg) divided twice daily and intramuscular gentamicin, 5 mg/kg once daily, both given for 7 days
• Experimental: procaine penicillin, gentamicin, and amoxicillin
  • procaine penicillin, 50,000 IU/kg once daily intramuscular injection plus gentamicin 5 mg/kg once daily intramuscular injection for 2 days, followed by 5 days of oral amoxicillin, 80-90 mg/kg divided in two doses.

Primary Measures

• Treatment failure
  • Time Frame: within 7 days of enrolment
    Safety Issue?: Yes

Inclusion Criteria:

Inclusion Criteria

• Infants 0-59 days old who are residents of catchment population of the study hospitals or clinics
• One or more of the following five signs: severe chest in-drawing, axillary temperature >38.0C or <35.50 C, movement only when stimulated, and history of feeding problems (confirmed by poor suck on feeding assessment)
• Family refuses recommended hospitalization or hospitalization otherwise not feasible
• Informed consent by a legal guardian.

Exclusion Criteria:

• Very severe infection/disease characterized by presence of any of the following signs (unconscious, convulsions, unable to feed, apnea, unable to cry, cyanosis, bulging fontanel, prolonged capillary refill, major congenital malformations, major bleeding, surgical conditions needing hospital referral, persistent vomiting defined as vomiting following three attempts to feed the baby within ½ hour)
• Very low birth weight: weight <1500
• Hospitalization for illness in the last two weeks
• Previous inclusion in the study

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 Investigator: Aga Khan University Other

Overall Clinical Trial Officials and Contacts

Overall Contact: Anita K.M Zaidi, MBBS, SM 92-21-3493-0051 anita.zaidi@aku.edu

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01027429

Study ID Number: SC134GL50124

ClinicalTrials.gov Identifier: NCT01027429

Health Authority: United States: International Technical Steering Committee appointed by Save the Children, USA, and