Prophylaxis of adrenal insufficiency to prevent CLD
Principal Investigator: K L Watterberg
Affiliation: University of New Mexico
Abstract: Chronic lung disease (CLD) is a frequent complication of prematurity, resulting in increased health care costs, prolonged hospital stay, frequent rehospitalizations, and compromised growth and development. Early treatment with dexamethasone may decrease CLD; however, this therapy has serious immediate and long-term adverse effects. Lung inflammation is a prominent early finding in the development of CLD. At the same time, many small premature infants show biochemical evidence and clinical signs consistent with adrenal insufficiency in the first week of life. Based on the hypothesis that early adrenal insufficiency results in amplified responses to inflammatory stimuli, and other physiologic disruptions, leading to ongoing lung injury and CLD, a randomized, blinded, placebo-controlled pilot study of 40 extremely low birth weight infants (ELBW, 500-999 g birth weight) was conducted. This study showed that hydrocortisone prophylaxis against adrenal insufficiency during the first two weeks of life resulted in a significant increase in survival without chronic lung disease. No increases in adverse outcomes were noted; however, the pilot study was not powerful enough to rule out a Type II error. Based on that hypothesis and pilot study, this application proposes a multicenter, randomized trial of 712 ELBW births, to further define the benefits and assess the risks of hydrocortisone prophylaxis against adrenal insufficiency in these infants. Primary outcome measures will be (1) benefit: increased survival without CLD at 36 weeks postmenstrual age; (2) risk: no increase in cerebral palsy at 18 22 months adjusted age. Other measures of neurodevelopmental outcome will also be assessed. The sample size will detect a change of 10 percentage points in successful outcome, and in the incidence of specific adverse effects, with a power of 80%. The hydrocortisone dose will be 1mg/kg/day for 12 days (equivalent to <10% of the typical starting dexamethasone dose), then 0.5mg/kg/day for 3 days. Baseline data on mother and infant, daily clinical data for the first 28 days of life, outcome data at 36 weeks postmenstrual age, and outcome data at 18 - 22 months adjusted age will be collected. Cortisol and cytokines (IL-1B, 1L6, and ILS) will be assayed at baseline and at 6 days of life. After therapy, cortisol response to ACTH will be assayed. If this study confirms the benefits seen in the pilot study, it will result in a significant improvement in health care for premature infants, both by introducing a beneficial new therapy, and by avoiding higher dose dexamethasone.
Funding Period: 2001-09-20 - 2007-06-30
more information: NIH RePORT
- Effect of dose on response to adrenocorticotropin in extremely low birth weight infantsKristi L Watterberg
Department of Neonatology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131 0001, USA
J Clin Endocrinol Metab 90:6380-5. 2005..Various cosyntropin doses are used to test adrenal function in premature infants, without consensus on appropriate dose or adequate response...
- Cardiac troponin T and cardiac dysfunction in extremely low-birth-weight infantsM A Cruz
Department of Pediatrics, Virginia Commonwealth University Medical Center, Richmond, VA 23298 0276, USA
Pediatr Cardiol 27:396-401. 2006....
- Joint distribution approaches to simultaneously quantifying benefit and riskMichele L Shaffer
Department of Health Evaluation Sciences, Penn State College of Medicine, Hershey, PA, USA
BMC Med Res Methodol 6:48. 2006..The ratio is calculated from the difference in risk and difference in benefit between therapies. Small sample sizes or expected differences in benefit or risk can lead to no solution or problematic solutions for confidence intervals...
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Department of Pediatrics Neonatology, MSC10 5590, 1 University of New Mexico School of Medicine, Albuquerque, NM 87131 0001, USA
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Division of Neonatology, Department of Pediatrics, University of New Mexico Children s Hospital, Albuquerque, NM 87131, USA
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