Effects of Melatonin as a Novel Antioxidant and Free Radicals Scavenger in Neonatal Sepsis
Condition: Neonatal Sepsis
MeSH terms: Sepsis; Toxemia; Neonatal Sepsis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Assess the efficacy of melatonin as an adjuvant in the treatment of free radical disease in
      septic preterms receiving melatonin compared to those on conventional treatment through
      measuring the level of Malondialdehyde as a marker of oxidative stress and by comparing other
      clinical and laboratory parameters of sepsis in both groups.
    

Detailed description: 
      This is a randomized controlled trial. It will be provisionally conducted on 55 neonates
      admitted to the neonatal intensive care units (NICUs) of Ain Shams University Hospitals,
      Cairo, Egypt.

      Inclusion criteria:

      The study will include:Preterm infants (less than 37 weeks gestational age). Evidence of
      neonatal sepsis.

      Exclusion Criteria: Neonate with evidence of any of the following will be excluded:

      Infants with hypoxic ischemic encephalopathy. Infants on nothing per os. Infants with high
      oxygen needs either on invasive or non-invasive mechanical ventilation.

      Group Classification:

      Studied neonates will be completely evaluated and subsequently discriminated, into 2 main
      groups:Sepsis group: including neonates with proved sepsis. These will be subsequently
      randomized by permuted block randomization according to sequence of enrollment into:Subgroup
      A: neonates with odd numbers will receive melatonin.

      Subgroup B: neonates with even numbers will not receive the medicine. Non Sepsis group:
      healthy neonates, in whom sepsis will be ruled-out on the basis of absence of any clinical or
      laboratory evidence suggestive of infection.

      Diagnosis of neonatal sepsis will be established based on the presence of: risk factors of
      sepsis (e.g., prematurity, chorioamnionitis), any clinical evidence suggestive of sepsis,
      quantitative C-reactive protein (CRP) levels ≥6 mg/dL, Rodwell's hematological scores ≥3,
      with or without positive blood culture results

        1. Comprehensive history taking including:

           A.Antenatal history: Maternal age, maternal diseases; Maternal diabetic control,
           maternal fever, infection, prolonged rupture of membranes >=18 hours, malodorous vaginal
           discharge.

           B.Natal history: Gestational age, sex, and mode of delivery. C.Postnatal history: APGAR
           score, Respiratory distress and/or cyanosis.

        2. Gestational age will be estimated using the date of the last menstrual period, early
           antenatal ultrasound if present when available and confirmed by the new Ballard scoring
           system

        3. Full clinical examination including: chest, cardiac, abdominal and neurological
           examination.

        4. Clinical signs of infection: lethargy, irritability, prolonged capillary refill,
           tachycardia, respiratory distress, apnea, convulsions, abdominal distension, feeding
           intolerance, hyperglycemia, temperature instability and bleeding.

        5. Assessment of the hemodynamic state of the neonates: mean arterial blood pressure
           (MABP), urinary output, temperature, capillary refill time.

        6. Laboratory investigations Complete blood picture (CBC) with differential leucocytic
           count. C- reactive protein (CRP) quantitative assay. Blood cultures. MDA assay: blood
           samples will be collected in plain tubes from peripheral veins or central venous access.
           Samples will be allowed to clot before centrifugation for 15 minutes and serum will be
           stored at (-20 degree C) until MDA analysis using MDA competitive ELISA-kit.

           Blood samples will be collected from all included neonates at enrollment and in day one
           for healthy group.

           As for subgroup A, other samples will be withdrawn at 4 and 72 hours after melatonin
           administration to assess serum level of malondialdehyde while for subgroup B another
           sample will be withdrawn after 72 hours

        7. Melatonin Medication:

           Melatonin 10 mg rapid release capsules (puritans pride) will be used. Melatonin will be
           given at a total dose of 20 mg dissolved in 4 ml of distilled water via enteral route in
           two doses of 10 mg each(2 ml ), with a 1-hour interval.(Gitto et al., 2000)

        8. Treatment protocol: All neonates will be managed according to the protocol of NICU
           beside routine neonatal care.

      Babies admitted to NICU will be bathed, placed in incubator, attached to monitor.

      Cannula will be inserted, IV fluids is started and IV antibiotics. If there is respiratory
      distress: O2 or ventilation is started, usually feeds are delayed to day 2 or day 3 (or even
      later) according the severity of condition (clinical decision according to the attending
      neonatologist).

      If no distress and the baby is well: trophic feeds will be started (10ml/kg/day milk), feeds
      are increased in 10-20ml/kg/day according to baby tolerance, and the condition of the baby
      (clinical decision according to the attending neonatologist), IV fluids are reduced
      gradually.
    

Intervention name(s): Melatonin 10 mg; Conventional treatment of neonatal sepsis
Intervention type(s): Drug; Combination Product
Intervention description(s): Melatonin will be given at a total dose of 20 mg dissolved in 4 ml of distilled water via enteral route in two doses of 10 mg each(2 ml ), with a 1-hour interval. to one group together with conventional treatment; Conventional treatment of neonatal sepsis including antibiotics,IV fluids, Total Parenteral Nutrition,etc...
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care