Early Blood Pressure Management in Extremely Premature Infants

Study Overview
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Brief Summary
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This trial tests the feasibility of enrolling 60 extremely preterm infants in a randomized, double-blinded study of blood pressure management within 12 months. Eligible infants will receive an infusion drug (dopamine or a dextrose placebo) and a syringe drug (hydrocortisone or a normal saline placebo). Enrolled infants will be randomized to receive one of the following drug pairs: dopamine and hydrocortisone dopamine and normal saline dextrose and hydrocortisone dextrose and normal saline. In addition to the intervention above, the NRN is conducting a 6-month time-limited prospective observational study of all infants born at an NRN center between 23 and 26 weeks gestational age. All clinical decisions made for these babies will be at the discretion of the attending neonatologist/infant care team according to standard practice at each institution. Data on blood pressure management in the first 24 postnatal hours collected for each infant.

Detailed Description
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Since most extremely preterm infants are critically ill in the immediate postnatal period, establishing normal blood pressure (BP) values is difficult. This lack of data makes deciding when to institute therapy for hypotension (low BP) challenging, leading to considerable variability in BP management in neonatal intensive care units (NICUs). Despite a lack of data on safety or efficacy, as many as 64% of extremely preterm infants receive inotropes (e.g., dopamine), and up to 12.4% of very low birthweight infants receive hydrocortisone for perceived hypotension. Since both untreated low BP and therapy provided for low BP may be harmful, the decision of whether to treat is an important issue. To date, no prospective randomized, controlled trial of BP management in this population has been performed. This trial tests the feasibility of enrolling up to 60 extremely preterm infants in a randomized, double-blinded study of blood pressure management within 12 months. It will enroll 60 infants between 23 0/7 and 26 6/7 weeks gestational age born at 6 participating NICHD Neonatal Research Network sites. Eligible infants will receive a study infusion drug (dopamine or a dextrose placebo) and a study syringe drug (hydrocortisone or a normal saline placebo). Infants will be randomized to receive one of the following drug pairs: (1) dopamine and hydrocortisone; (2) dopamine and a placebo (normal saline solution); (3) a placebo (dextrose) and hydrocortisone; or (4) placebo (dextrose) and placebo (normal saline). (NOTE: dopamine is normally mixed with dextrose and hydrocortisone is mixed with saline solution before being administered, which is why two different placebos are being used in this trial.) The information gathered will provide a framework for the design of a potential larger, multi-centered, randomized control trial. NOTE: The NICHD Neonatal Research Network has received a FDA exemption from the IND regulations for this trial. In addition to the interventional trial above, the NRN is conducting a 6-month time-limited prospective observational study of all infants born at an NRN center between 23 and 26 weeks gestational age. All clinical decisions made for these babies will be at the discretion of the attending neonatologist/infant care team according to standard practice at each institution. Data on blood pressure management in the first 24 postnatal hours collected for each infant. Based on slow rate of recruitment, a time-limited observational study of hypotension in ELBW infants has been added to the current study.

Official Title
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Early Blood Pressure Management in Extremely Preterm Infants Feasibility Pilot Study

Conditions
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Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Hypotension, Blood Pressure

Intervention / Treatment
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* Drug: Dopamine
* Drug: Hydrocortisone
* Drug: Infusion Placebo
* Drug: Syringe Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inborn infants 23 0/7 to 26 6/7 weeks estimated gestational age Umbilical arterial catheter in place at study entry <= 24 hours of age Exclusion Criteria: Terminally ill infants Infants that have received (prior to enrollment): >20 ml/kg in fluid boluses, indomethacin, or ibuprofen Infants with major congenital anomalies

Ages Eligible for Study
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Maximum Age: 24 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dopamine and hydrocortisone<br>Dopamine AND hydrocortisone | Drug: Dopamine<br>* Dopamine<br>Drug: Hydrocortisone<br>* Hydrocortisone<br>|
| Active Comparator: Dopamine and placebo<br>Dopamine AND normal saline placebo | Drug: Dopamine<br>* Dopamine<br>Drug: Syringe Placebo<br>* Normal saline<br>|
| Active Comparator: Placebo and hydrocortisone<br>Dextrose (D5W) placebo AND hydrocortisone | Drug: Hydrocortisone<br>* Hydrocortisone<br>Drug: Infusion Placebo<br>* Dextrose (D5W)<br>|
| Placebo Comparator: Placebo and Placebo<br>Dextrose (D5W) placebo AND normal saline placebo | Drug: Infusion Placebo<br>* Dextrose (D5W)<br>Drug: Syringe Placebo<br>* Normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrollment and completion of 60 infants |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death |  | 1 week and prior to hospital discharge | 
| Duration of antihypotensive therapy |  | First 96 postnatal hours | 
| Receipt and timing of medical and/or surgical therapy for a PDA |  | To hospital discharge | 
| Use of open-label antihypotensive therapies (inotropes, corticosteroids, blood and plasma volume expanders) for persistently low BP with biochemical evidence of poor perfusion |  | First 96 postnatal hours | 
| Spontaneous gastrointestinal perforation |  | First 7 days | 
| In-hospital complications (grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis requiring surgical intervention, retinopathy of prematurity requiring laser surgery, or bronchopulmonary dysplasia) |  | To hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NICHD Neonatal Research Network, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity, Blood Pressure Management, Dopamine, Hydrocortisone