Simplified Antibiotic Regimens for Outpatient Treatment of Suspected Sepsis in Neonates and Young Infants in Bangladesh

NCT00844337 | Completed DMC

• 2 other identifiers: JHU IRB 1440USAID GHS-A-00-09-00004-00
• Study Type: interventional
• Target: 2,490
• Locations: 1 country
• Sites: 3

Brief Summary

The primary aim is to establish the non-inferiority of several simplified, home-based antibiotic regimens compared to the standard course of parenteral antibiotics for the empiric treatment of suspected sepsis in Bangladeshi young infants whose parents refuse hospitalization. Three alternative regimens will be compared with a standard (reference) regimen of injectable procaine-benzyl penicillin and gentamicin once daily each for seven days. Alternative regimens are (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 (3) injectable gentamicin once daily and oral amoxicillin twice daily for two days followed by oral amoxicillin twice daily for five days. Hypothesis The proportion who fails treatment will be 10 percent in the reference group and the alternative treatment groups. An alternative therapy will be considered non-inferior to the standard therapy if the failure rate in the alternative therapy exceeds the failure rate in the injectable therapy by less than 5 absolute percentage points. Secondary Objectives:

• To identify baseline clinical predictors of treatment failure in severe infections in young infants.
• To determine the proportion of relapse (young infants who were considered cured by day 7 but developed any of the signs of suspected severe infection by day 14).

Conditions

Sepsis

Keywords

antibiotic regimens; sepsis; young infants; Bangladeshi; outpatient treatment; Suspected sepsis in young infants

Outcome Measures

Primary Outcomes (1)

• Treatment failure

  Seven days

Study Arms (3)

1

ACTIVE COMPARATOR

One study arm will receive injectable gentamicin once daily and oral amoxicillin twice daily for seven days by comparison to other study arms.

Drug: Gentamicin & Amoxicillin x 7days

2

ACTIVE COMPARATOR

Injectable penicillin and gentamicin once daily for two days followed by oral amoxicillin twice daily for five days

Drug: Penicillin & gentamicin x 2 d + Amoxicillin X 5 d

3

ACTIVE COMPARATOR

Injectable procaine-benzyl penicillin and gentamicin once daily each for seven days (COMPARISON ARM)

Drug: Standard reference therapy

Interventions

Gentamicin & Amoxicillin x 7days DRUG

Injectable gentamicin once daily and oral amoxicillin twice daily for seven days. The dose for gentamicin is 4 - 5 mg/kg/24 hours. The dose for amoxicillin is 90-115 mg/kg/day.

Also known as: Gentamicin & Amoxicillin

1

Penicillin & gentamicin x 2 d + Amoxicillin X 5 d DRUG

Injectable penicillin and gentamicin once daily for two days followed by oral amoxicillin twice daily for five days. The dose for penicillin is 40,000 - 50,000 U/kg/24 hours, the dose for gentamicin is 4 - 5 mg/kg/24 hours, and the dose for amoxicillin is 90-115 mg/kg/day.

Also known as: Penicillin, Gentamicin

2

Standard reference therapy DRUG

Injectable procaine-benzyl penicillin and gentamicin once daily each for seven days. The penicillin dose is 40,000 - 50,000 U/kg/24 hours, and the gentamicin dose is 4 - 5 mg/kg/24 hours.

3

Eligibility Criteria

• Age: Up to 59 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants 0-59 days old who are residents of catchment population of the study hospitals
• One or more of the following five signs: severe chest in-drawing, axillary temperature \>37.80C or \<35.50 C, lethargic or less than normal movement, 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.

You may not qualify if:

• 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, 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, and/or physician's suspicion of meningitis)
• Very low birth weight: weight \<1500
• Hospitalization for illness in the last two weeks
• Hospital born infants

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• Dhaka Shishu Hospital: collaborator

Study Sites (3)

Dhaka Shishu Hospital/CHRF

Dhaka, Dhaka Division, 1216, Bangladesh

Location

Chittagong Ma O Shishu Hospital

Chittagong, Bangladesh

Location

Shishu Shastya Foundation

Dhaka, Bangladesh

Location

Related Publications (3)

• Longombe AL, Ayede AI, Marete I, Mir F, Ejembi CL, Shahidullah M, Adejuyigbe EA, Wammanda RD, Tshefu A, Esamai F, Zaidi AK, Baqui AH, Cousens S. Oral amoxicillin plus gentamicin regimens may be superior to the procaine-penicillin plus gentamicin regimens for treatment of young infants with possible serious bacterial infection when referral is not feasible: Pooled analysis from three trials in Africa and Asia. J Glob Health. 2022 Nov 21;12:04084. doi: 10.7189/jogh.12.04084.

  PMID: 36403158 DERIVED

• Baqui AH, Saha SK, Ahmed AS, Shahidullah M, Quasem I, Roth DE, Samsuzzaman AK, Ahmed W, Tabib SM, Mitra DK, Begum N, Islam M, Mahmud A, Rahman MH, Moin MI, Mullany LC, Cousens S, El Arifeen S, Wall S, Brandes N, Santosham M, Black RE; Projahnmo Study Group in Bangladesh. Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial. Lancet Glob Health. 2015 May;3(5):e279-87. doi: 10.1016/S2214-109X(14)70347-X. Epub 2015 Apr 1.

  PMID: 25841891 DERIVED

• Baqui AH, Saha SK, Ahmed AS, Shahidullah M, Quasem I, Roth DE, Williams EK, Mitra D, Shamsuzzaman AK, Ahmed W, Mullany LC, Cousens S, Wall S, Brandes N, Black RE. Safety and efficacy of simplified antibiotic regimens for outpatient treatment of serious infection in neonates and young infants 0-59 days of age in Bangladesh: design of a randomized controlled trial. Pediatr Infect Dis J. 2013 Sep;32 Suppl 1(Suppl 1 Innovative Treatment Regimens for Severe Infections in Young Infants):S12-8. doi: 10.1097/INF.0b013e31829ff790.

  PMID: 23945570 DERIVED

MeSH Terms

Conditions

Sepsis

Interventions

Gentamicins; Amoxicillin; Penicillins

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates; Ampicillin; Penicillin G; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Abdullah H Baqui, MBBSMPHDrPH

  Johns Hopkins University Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 13, 2009
• First Posted: February 16, 2009
• Study Start: March 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 16, 2014

Record last verified: 2014-09

Locations

BA (3)