SATT: Simplified Antibiotic Therapy for Sepsis in Young Infants

Sponsor

Aga Khan University (Other)

Overall Status

Completed

CT.gov ID

NCT01027429

Collaborator

Save the Children (Other), World Health Organization (Other), London School of Hygiene and Tropical Medicine (Other), Emory University (Other)

2,543

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neonatal Sepsis Sepsis Infection	Drug: procaine penicillin and gentamicin Drug: amoxicillin and gentamicin Drug: procaine penicillin, gentamicin, amoxicillin	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

2543 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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	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: 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.
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	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.
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.	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.

Arm

Intervention/Treatment

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

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: 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.

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

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

Experimental: procaine penicillin, gentamicin, and amoxicillin

Drug: procaine penicillin, gentamicin, amoxicillin

Outcome Measures

Primary Outcome Measures

Treatment failure [within 7 days of enrolment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 59 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)