Health Condition 1: P369- Bacterial sepsis of newborn, unspecified Health Condition 2: A418- Other specified sepsis
Conditions
Interventions
Intervention1: Amikacin solution for Injection or Infusion
Flomoxef powder for Intravenous Injection
Fosfomycin: powder for solution for infusion
Ampicillin powder for solution for injection
Amoxicill
Sponsors
Global Antibiotic Research and Development Partnership (GARDP)
Novotech Clinical Research India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Currently admitted to hospital 2. Aged less than or equal to 28 days (post-natal age) 3. Weight greater than or equal to 1000gram 4. Clinical diagnosis of a new episode of sepsis with two or more of the following clinical signs together with planned treatment with IV antibiotics a. Abnormal temperature (less than 35.5 degree Celsius Or greater than or equal to 38degree celsius) b. Chest indrawing or increase in oxygen requirement or increase of respiratory support c. Abdominal distension d. Difficulty in feeding or feeding intolerance e. Evidence of shock including cold peripheries f. Lethargy, or reduced or no spontaneous movement g. Cyanosis h. Abnormal heart rate (bradycardia less than 80 Beats Per Minute; tachycardia greater than 80 Beats Per Minute) i. Convulsions j. Irritability For making the diagnosis of significant sepsis, the neonate should have no alternative primary explanation for these criteria (such as Hypoxic Ischaemic Encephalopathy, hypothermia, hypoglycemia, prematurity etc) 5. At moderate to high risk of death from this episode of sepsis, based on a neonatal sepsis severity score (NeoSep Severity Score). This was adapted from the WHO Possible serious bacterial infection based scores for the hospital setting and developed using baseline clinical information and subsequent mortality from the Neonatal observational study study; specifically, a NeoSep Severity Score of 5 or higher at presentation for this episode of sepsis (which may be before formal screening) 6. Can receive all potential treatment options on the relevant randomisation list for this neonate at their site, ensuring randomisation is possible see country-specific appendices 7. Intravenous antibiotics about to be started OR not received more than 24 hours of Intravenous antibiotics for this episode of neonatal sepsis at the point of randomisation 8. Parent or guardian willing and able to provide consent (written or, if their neonate is severely ill, verbal consent which must be confirmed by written consent as soon as possible and wherever possible within 48 hours after the first trial specific procedure). Verbal consent allows for administration of first-line antibiotics at no or minimal delay.
Exclusion criteria
Exclusion criteria: 1. A known serious, non-infective co-morbidity anticipated to cause death within this admission (including major congenital abnormalities anticipated to cause death within this admission other than prematurity, e.g. known large ventricular septal defect) 2. Previously enrolled in this trial 3. Current participation in any other clinical study of an Investigational Medicinal Product (IMP) that is a systemic drug, unless it has received prior approval by the NeoSep1 Trial Management Group (TMG) 4. Known contraindication to any of the trial antibiotics on the randomisation list for the relevant neonatal sub-population in that site.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 28-day mortalityTimepoint: Baseline to Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical status, assessed daily after randomisation through to the earlier of discharge from a trial site or Day 28 using a clinical recovery score based on data from the NeoOBS observational studyTimepoint: Baseline to Day 28;Additional systemic antibiotics beyond the first randomised treatment through Day 28Timepoint: Baseline to Day 28;Additional systemic antibiotics beyond the first randomised and second (for failure) treatment through Day 28Timepoint: Baseline to Day 28;Length of stay during the index hospitalisationTimepoint: Baseline to Day 28;Systemic antibiotic exposure (days on antibiotics) during the index hospitalisationTimepoint: Baseline to Day 28;90-day mortalityTimepoint: Day 29 to Day 90;Change in C-reactive protein to Day 3 and 7 from baselineTimepoint: Baseline to Day 3 and day 7;Grade 3/4 adverse events (AEs) graded using a combined low and middle income country (LMIC) relevant adapted Division of AIDS (DAIDS) and International Neonatal Consortium Neonatal Adverse Event Severity Scale (NAESS) through Day 28Timepoint: Baseline to Day 28;Adverse events of any grade related to antibiotics through Day 28Timepoint: Baseline to Day 28;Modification (including discontinuation) of antibiotics for adverse reactions through Day 28Timepoint: Baseline to Day 28;Neurodevelopment as assessed by the WHO Global Scale for Early Development (GSED) package at Day 28 and Day 90Timepoint: Day 28 and Day 90;Re-admission by Day 90 (all-cause)Timepoint: Discharge to Day 90 | — |
Countries
Bangladesh, Ghana, India, Kenya, Pakistan, South Africa, Uganda, Viet Nam
Contacts
Public ContactKanhaiya Choudhary
Novotech India Private Limited
Outcome results
None listed