Early Use of Hydrocortisone in Hypotensive Very Low Birth Weight Infants
Condition: Neonatal Hypotension
MeSH terms: Hypotension; Birth Weight
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to investigate the early use of hydrocortisone in hypotensive
      very low birth weight infants.

      Based on the observations that:

        -  hypotension is a common problem in very low birthweight infants and is associated with
           brain injury and poor neurological outcomes;

        -  some infants are refractory to standard treatment (volume expansion and vasopressors),
           which is not exempt of adverse effects;

        -  relative adrenal insufficiency has been described in this population; we hypothesize
           that hydrocortisone is effective in the treatment of hypotension in this population and
           reduce the need for vasopressors.
    

Detailed description: 
      Eligible infants will be randomly assigned to receive hydrocortisone or placebo, using
      sequentially numbered, preassigned treatment designations in sealed, opaque envelopes. The
      study drug will be randomly assigned to each patient number, in advance, using a
      computer-based random number generator.

      Hydrocortisone and placebo doses will be prepared and provided by the hospital pharmacy
      following the assigned study number. Active and placebo drug solutions will be completely
      indistinguishable.

      Infants of multiple gestations will be randomized as separate subjects. Crossover between
      study groups is not allowed. Physicians involved in the care of the infants will be blinded
      to treatment group allocation.

      If the infant remains hypotensive after a Normal Saline (NS) bolus 10 ml/kg, blood for serum
      cortisol level determination will be drawn and hydrocortisone or an equivalent volume of NS
      placebo will be administered intravenously as follows: first dose immediately after
      randomization 2 mg/kg; 6 hours after 1 mg/kg q6h for 3 doses; followed by 0.5 mg/kg q6hs for
      4 doses. If an infant responds to the initial dose of NS but becomes hypotensive within 1
      hour after will also be randomized, otherwise another NS bolus could be administered.

      Initiation and escalation of inotropes:

      Concurrently with the first dose of study drug, dopamine infusion will be started at 5
      mcg/kg/minute, increasing stepwise to a maximum of 15 mcg/kg/minute. If hypotension persists
      an epinephrine infusion at 0.05 mcg/kg/min will be added and increased stepwise if necessary.
      The aim is to maintain mean blood pressure (MBP) above the hypotensive limit defined in the
      inclusion criteria.

      Weaning of inotropes:

      Once normotension has been maintained for 1 hour or MBP > 40 mmHg for 15 minutes, weaning
      should be started. Dopamine infusion will be reduced first, as tolerated, to 5 mcg/kg/minute.
      If the subject is on epinephrine infusion the dose will be reduced stepwise to 0.05
      mcg/kg/minute and discontinued. When the subject is off epinephrine and/or dopamine at 5
      mcg/kg/minute, dopamine will be discontinued. If at any time hypotension recurs, weaning
      should be held and increased inotropes dose as per escalation algorithm.
    

Intervention name(s): Hydrocortisone
Intervention type(s): Drug
Intervention description(s): See detailed description above.
Intervention MeSH terms: Hydrocortisone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Preterm; hypotension; steroids; hydrocortisone