Clinical trial NCT01027429: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neonatal Sepsis
Sepsis
Infection
Keywords: infant
newborn
sepsis
infection
community
Lead sponsor: Aga Khan University
Sponsor class: OTHER
Collaborators: name: Save the Children
name: World Health Organization
name: London School of Hygiene and Tropical Medicine
name: Emory University
First posted: 2009-12-08
Enrollment: 2543
Sex: ALL
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment failure
timeFrame: within 7 days of enrolment
Secondary outcomes:
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Ali Akber Shah Goth
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Shiyam S Sunder, MBBS
role: STUDY_DIRECTOR
References:
citation: Mir F, Pearce RE, Baig-Ansari N, Qazi S, Barrett JS, Abdel-Rahman S, Kearns G, Zaidi AK. Serum amoxicillin levels in young infants (0-59 days) with sepsis treated with oral amoxicillin. Arch Dis Child. 2020 Dec;105(12):1208-1214. doi: 10.1136/archdischild-2019-317342. Epub 2020 May 13.
citation: Mir F, Nisar I, Tikmani SS, Baloch B, Shakoor S, Jehan F, Ahmed I, Cousens S, Zaidi AK. Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial. Lancet Glob Health. 2017 Feb;5(2):e177-e185. doi: 10.1016/S2214-109X(16)30335-7. Epub 2016 Dec 15.
citation: Zaidi AK, Tikmani SS, Sultana S, Baloch B, Kazi M, Rehman H, Karimi K, Jehan F, Ahmed I, Cousens S. Simplified antibiotic regimens for the management of clinically diagnosed severe infections in newborns and young infants in first-level facilities in Karachi, Pakistan: study design for an outpatient randomized controlled equivalence trial. Pediatr Infect Dis J. 2013 Sep;32 Suppl 1(Suppl 1 Innovative Treatment Regimens for Severe Infections in Young Infants):S19-25. doi: 10.1097/INF.0b013e31829ff7aa.