Early Use of Hydrocortisone in Hypotensive Very Low Birth Weight Infants

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.

Study Overview

• Status: Completed
• Conditions: Neonatal Hypotension
• Intervention / Treatment: Drug: Hydrocortisone

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Division of Neonatology, Children's and Women's Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gestational age ≤ 30 weeks, Birth weight ≤ 1250 grams and ≤ 48 hours age;
• Umbilical or peripheral arterial catheter in place;
• Invasive mean blood pressure < gestational age in completed weeks after 1 Normal Saline bolus 10 ml/kg;
• Parental/legal guardian consent.

Exclusion Criteria:

• Clear evidence of hypovolemia (blood loss);
• Chromosomal abnormalities;
• Hydrops fetalis;
• Major congenital anomalies;
• Cardiac lesions other than patent ductus arteriosus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total cumulative dose of dopamine at 48 hours of study drug administration and by day 7 of life	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Total cumulative dose of epinephrine and total dose of fluids at 48 hours of study drug administration and by day 7 of life	7 days

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: BC Research Inc.
• Investigators: Principal Investigator: Horacio Osiovich, MD, The University of British Columbia

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: July 28, 2006
• First Submitted That Met QC Criteria: July 28, 2006
• First Posted (Estimate): August 1, 2006

Study Record Updates

• Last Update Posted (Estimate): April 12, 2011
• Last Update Submitted That Met QC Criteria: April 11, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: hydrocortisone; steroids; Preterm; hypotension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Body Weight; Birth Weight; Hypotension; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: C05-0006