Simplified Antibiotic Therapy for Sepsis in Young Infants

Phase 3

Completed

• Conditions: Neonatal Sepsis; Sepsis; Infection
• Interventions: Drug: procaine penicillin and gentamicin; Drug: amoxicillin and gentamicin; Drug: procaine penicillin, gentamicin, amoxicillin

• Registration Number: NCT01027429
• Lead Sponsor: Aga Khan University

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2009-12-07
• Study First Submitted QC: 2009-12-07
• Study First Posted: 2009-12-08
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-26
• Last Update Posted: 2015-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2543

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
procaine penicillin and gentamicin	procaine penicillin, gentamicin, amoxicillin	Procaine penicillin, 50,000 IU/kg by intramuscular injection plus gentamicin, 5 mg/kg intramuscular injection, both given once daily for 7 days
procaine penicillin and gentamicin	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
Amoxicillin and gentamicin	procaine penicillin, gentamicin, amoxicillin	Oral amoxicillin (80-90 mg/kg) divided twice daily and intramuscular gentamicin, 5 mg/kg once daily, both given for 7 days
Amoxicillin and gentamicin	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
procaine penicillin, gentamicin, and amoxicillin	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.

Primary Outcome Measures

Name	Time	Method
Treatment failure	within 7 days of enrolment

Trial Locations

Locations (1)

Ali Akber Shah Goth; 🇵🇰 Karachi, Sindh, Pakistan