Trial record 17 of 466 for:    pharmacology + NICHD

Dexamethasone Therapy in VLBW Infants at Risk of CLD

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00011362
First received: February 15, 2001
Last updated: January 9, 2011
Last verified: September 2010
  Purpose

Infants who are on breathing support are often treated with steroids (dexamethasone); however, the best timing of therapy is not known. This trial looked at the benefits and hazards of starting dexamethasone therapy at two weeks of age and four weeks of age in premature infants.


Condition Intervention Phase
Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Bronchopulmonary Dysplasia
Drug: Dexamethasone Early
Drug: Dexamethasone Late
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial of Dexamethasone Therapy in Very-Low-Birth-Weight Infants at Risk for Chronic Lung Disease (CLD)

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Number of days from randomization to ventilator independence, defined as extubation not requiring reintubation, or extubation followed by elective reintubation for seven days or less so that the infant could undergo a surgical procedure [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Death before discharge from the hospital [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
  • Duration of assisted ventilation [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
  • Duration of supplemental oxygen therapy [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
  • Duration of hospital stay [ Time Frame: At hospital discharge ] [ Designated as safety issue: No ]
  • Incidence of chronic lung disease [ Time Frame: At hospital discharge ] [ Designated as safety issue: Yes ]
  • Morbidity and mortality from respiratory causes during the first year [ Time Frame: 12 months of age ] [ Designated as safety issue: Yes ]

Enrollment: 371
Study Start Date: September 1992
Study Completion Date: April 1994
Primary Completion Date: January 1994 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dexamethasone
Dexamethasone
Drug: Dexamethasone Early
Tapering course of dexamethasone in doses given twice a day (0.25 mg per kilogram of body weight per dose for five days, then 0.15 mg, 0.07 mg, and 0.03 mg per kilogram per dose for three days each), followed by two weeks of saline.
Drug: Dexamethasone Late
Saline for two weeks, followed by either the same tapering two-week course of dexamethasone given to the first group, if the respiratory-index score was >=2.4 on treatment day 14, or an additional two weeks of saline
Placebo Comparator: Placebo
Saline
Drug: Dexamethasone Early
Tapering course of dexamethasone in doses given twice a day (0.25 mg per kilogram of body weight per dose for five days, then 0.15 mg, 0.07 mg, and 0.03 mg per kilogram per dose for three days each), followed by two weeks of saline.
Drug: Dexamethasone Late
Saline for two weeks, followed by either the same tapering two-week course of dexamethasone given to the first group, if the respiratory-index score was >=2.4 on treatment day 14, or an additional two weeks of saline

Detailed Description:

Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 grams) who had respiratory-index scores (mean airway pressure x the fraction of inspired oxygen) of greater than or equal 2.4 at two weeks of age. The primary outcome was the number of days from randomization to extubation not requiring reintubation (extubation score or death). The secondary outcomes were death before discharge from the hospital; the duration of assisted ventilation, supplementary oxygen therapy and hospital stay; the incidence of chronic lung disease (defined as the need for supplemental oxygen at 36 weeks postconceptional age by best obstetrical estimate) and rates of morbidity and mortality from respiratory causes during the first year. Additional secondary endpoints were hyperglycemia, hypertension, growth, bacteremia, necrotizing enterocolitis and upper GI bleeding.

The sample size of 370 was based on a 0.60 probability that the extubation score of late treatment was greater than early treatment, a 5% two-sided type 1 error, 85% power, and 10% treatment noncompliance.

Infants were randomized to either receive dexamethasone for two weeks followed by saline placebo for two weeks, or saline placebo for two weeks followed by either dexamethasone or additional placebo for two weeks (if they still met entry criteria). Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose then tapered.

The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P less than 0.001) in both groups. Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of age.

  Eligibility

Ages Eligible for Study:   up to 15 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 501 to 1500 grams
  • 13 to 15 days old
  • Respiratory-index score of greater than or equal to 2.4 that had been increasing or minimally decreasing during the previous 48 hours or a score of greater than or equal to 4.0 even if there had been improvement during the preceding 48 hours

Exclusion criteria:

  • Received glucocorticoid treatment after birth
  • Had evidence or suspicious signs of sepsis as judged by the treating physician
  • Major congenital anomaly of the cardiovascular, pulmonary, or central nervous system
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00011362

Locations
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, District of Columbia
George Washington University
Washington, District of Columbia, United States, 20052
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Tennessee
University of Tennessee
Memphis, Tennessee, United States, 38163
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Investigators
Principal Investigator: Lu-Ann Papile, MD University of New Mexico
Principal Investigator: Jon E. Tyson, MD MPH University of Texas Southwestern Medical Center
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: Edward F. Donovan, MD Cincinnati Children's Medical Center
Principal Investigator: Charles R. Bauer, MD University of Miami
Principal Investigator: Sheldon B. Korones, MD University of Tennessee Health Science Center
Principal Investigator: James A. Lemons, MD Indiana University School of Medicine
Principal Investigator: Avroy A. Fanaroff, MD Rainbow Babies & Children's Hospital, Case Western Reserve University
Principal Investigator: David K. Stevenson, MD Stanford University
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: William Oh, MD Women & Infants' Hospital, Brown University
Principal Investigator: Richard A. Ehrenkranz, MD Yale University
  More Information

Additional Information:
Publications:
Responsible Party: Lu-Ann Papile/ Lead Principal Investigator, University of New Mexico
ClinicalTrials.gov Identifier: NCT00011362     History of Changes
Other Study ID Numbers: NICHD-NRN-0005, U10HD027881, U10HD021373, U10HD027851, U10HD027853, U10HD021397, U01HD019897, U10HD021415, U10HD027856, U10HD021364, U10HD027880, U10HD027904, U10HD027871, U10HD021385, M01RR000997, M01RR008084, M01RR000750, M01RR000070, M01RR006022
Study First Received: February 15, 2001
Last Updated: January 9, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Prematurity
Dexamethasone
Glucocorticoids
Respiratory Distress Syndrome
Respiratory insufficiency
Steroids

Additional relevant MeSH terms:
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Birth Weight
Bronchopulmonary Dysplasia
Body Weight
Signs and Symptoms
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014