ELGAN BP: Early Blood Pressure Management in Extremely Premature Infants

Sponsor

NICHD Neonatal Research Network (Other)

Overall Status

Completed

CT.gov ID

NCT00874393

Collaborator

National Center for Research Resources (NCRR) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Enrollment

Locations

Arms

Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Hypotension Blood Pressure	Drug: Dopamine Drug: Hydrocortisone Drug: Infusion Placebo Drug: Syringe Placebo	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Early Blood Pressure Management in Extremely Preterm Infants Feasibility Pilot Study

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dopamine and hydrocortisone Dopamine AND hydrocortisone	Drug: Dopamine Dopamine Drug: Hydrocortisone Hydrocortisone
Active Comparator: Dopamine and placebo Dopamine AND normal saline placebo	Drug: Dopamine Dopamine Drug: Syringe Placebo Normal saline
Active Comparator: Placebo and hydrocortisone Dextrose (D5W) placebo AND hydrocortisone	Drug: Hydrocortisone Hydrocortisone Drug: Infusion Placebo Dextrose (D5W)
Placebo Comparator: Placebo and Placebo Dextrose (D5W) placebo AND normal saline placebo	Drug: Infusion Placebo Dextrose (D5W) Drug: Syringe Placebo Normal saline

Outcome Measures

Primary Outcome Measures

Enrollment and completion of 60 infants [1 year]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 24 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	Yale University	New Haven	Connecticut	United States	06504
4	Emory University	Atlanta	Georgia	United States	30303
5	Indiana University	Indianapolis	Indiana	United States	46202
6	University of Iowa	Iowa City	Iowa	United States	52242
7	Tufts Medical Center	Boston	Massachusetts	United States	02111
8	Wayne State University	Detroit	Michigan	United States	48201
9	University of New Mexico	Albuquerque	New Mexico	United States	87131
10	RTI International	Durham	North Carolina	United States	27705
11	Duke University	Durham	North Carolina	United States	27710
12	Cincinnati Children's Medical Center	Cincinnati	Ohio	United States	45267
13	Case Western Reserve University	Cleveland	Ohio	United States	44106
14	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
15	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
16	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
17	University of Utah	Salt Lake City	Utah	United States	84108

Sponsors and Collaborators

NICHD Neonatal Research Network
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator: Beau J. Batton, MD, Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: Ronald N. Goldberg, MD, Duke University
Principal Investigator: Krisa P. Van Meurs, MD, Stanford University
Principal Investigator: Waldemar A Carlo, MD, University of Alabama at Birmingham
Principal Investigator: Kristi L. Watterberg, MD, University of New Mexico
Principal Investigator: Roger G. Faix, MD, University of Utah
Principal Investigator: Abhik Das, PhD, RTI International
Principal Investigator: Edward F. Bell, MD, University of Iowa
Principal Investigator: Abbot R. Laptook, MD, Brown University
Principal Investigator: Barbara J. Stoll, MD, Emory University
Principal Investigator: Brenda P. Poindexter, MD MS, Indiana University
Principal Investigator: Kurt Schibler, MD, Children's Hospital Medical Center, Cincinnati
Principal Investigator: Kathleen A. Kennedy, MD MPH, The University of Texas Health Science Center, Houston
Principal Investigator: Pablo J. Sanchez, MD, University of Texas
Principal Investigator: Seetha Shankaran, MD, Wayne State University
Principal Investigator: Richard A. Ehrenkranz, MD, Yale University
Principal Investigator: Ivan D. Franz III, MD, Tufts University