Cytokine Change in Bronchoalveolar Lavage Fluid After Early Budesonide-Surfactant Treatment in Premature Infants

This study has been terminated.
Sponsor:
Information provided by:
China Medical University Hospital
ClinicalTrials.gov Identifier:
NCT00146497
First received: September 4, 2005
Last updated: June 26, 2006
Last verified: June 2006
  Purpose

Pulmonary inflammation plays an important role in the development of chronic lung disease (CLD) in preterm infants. This inflammation occurs very early in postnatal life. Any therapy that could be beneficial in preventing CLD should be started very early. The investigators' previous double-blind study has shown that early (< 12 hours) postnatal use of intravenous dexamethasone for 4 weeks significantly suppressed pulmonary inflammation and significantly reduced the incidence of CLD. However, the use of dexamethasone was associated with increased incidence of infection and sepsis. Their follow-up study also suggested an increase in the incidence of psychomotor anomalies. As compared to intravenous administration, endotracheal instillation will provide more local anti-inflammatory effects and less systemic side effects. Infants will be eligible for the study if their birth weight (BW) is < 1500 gm and if they had severe respiratory distress syndrome (RDS) requiring mechanical ventilation shortly after birth. After informed consent is obtained, the infant will be randomly assigned depending on the condition of the infant. The primary outcome is the change in cytokines (interleukin-6, 8, 10 and TNF-α) levels in BAL fluid. Chronic lung disease (CLD) was judged at 36 postmenstrual weeks. Infants in the study group (S/B group) received surfactant (Survanta®, Abbott Laboratories, North Chicago, IL; 100 mg or 4 mL/kg/dose) and Budesonide (Pulmicort®, AstraZeneca Pty Ltd., Australia; 0.5 mg or 1mL/kg/dose), while those in the control group (S group) received surfactant (Survanta® Abbott, 100 mg/kg/dose) and saline (1mL/kg).


Condition Intervention Phase
Premature Infants
Respiratory Distress Syndrome
Chronic Lung Disease
Bronchoalveolar Lavage Fluid
Cytokines
Drug: Budesonide-Surfactant
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention

Resource links provided by NLM:


Further study details as provided by China Medical University Hospital:

Primary Outcome Measures:
  • The primary outcome variables are the levels of proinflammatory cytokines IL-6, IL-8 and TNF-α and anti-inflammatory cytokine IL-10.

Secondary Outcome Measures:
  • The secondary outcome is the clinical endpoint of survival free of oxygen dependence at 36 wks postmenstrual age.

Estimated Enrollment: 30
Study Start Date: August 2004
Detailed Description:

Growing evidence suggests that early, postnatal pulmonary inflammation may play an important role in the development of chronic lung disease (CLD) in preterm infants on mechanical ventilation.The investigator's previous study demonstrated that interleukin-8 (IL-8), a marker of inflammation, in bronchoalveolar lavage (BAL) fluid increased by as early as 2 days of age in infants who subsequently developed CLD compared with infants who did not develop the disease. Thus for any therapy to be beneficial in preventing CLD, it should be started very early. Early postnatal use of intravenous dexamethasone therapy for 4 weeks significantly suppressed pulmonary inflammation and significantly reduced the incidence of CLD. However, the use of dexamethasone was associated with increased incidence of infection and sepsis which affected the immediate outcome and contributed significantly to mortality. It was shown that school age children who had received early postnatal dexamethasone therapy for the prevention of CLD showed a significant increase in incidence of neuromotor and cognitive delay. Based on the results of these studies, early systemic dexamethasone therapy should not be recommended. Budesonide has high local anti-inflammatory activity and is one of the most extensively used inhaled glucocorticoids. Budesonide decreases airway hyperresponsiveness and reduces the number of inflammatory cells and mediators present in the airways of patients with asthma. A previous study indicated that the addition of Budesonide to Survanta did not affect the surface tension. We proposed a randomized controlled trial to study whether early endotracheal instillation of Surfactant-Budesonide (S/B) mixture would reduce lung inflammation and improve pulmonary outcome. We will measure the cytokines levels in BAL fluid to evaluate the local anti-inflammatory effect of S/B treatment.

  Eligibility

Ages Eligible for Study:   up to 1 Day
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Preterm infants with birth weight between 500-1500 gm
  • Have severe radiographic RDS and require mechanical ventilation within 4 hours after birth

Exclusion Criteria:

  • Presence of prenatal infection, congenital anomalies and lethal cardio-pulmonary status.
  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: NCT00146497

Locations
Taiwan
China Medical University Hospital
Taichung, Taiwan
Sponsors and Collaborators
China Medical University Hospital
Investigators
Principal Investigator: Tsu-Fuh Yeh, MD China Medical University Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00146497     History of Changes
Other Study ID Numbers: DMR92-IRB-127
Study First Received: September 4, 2005
Last Updated: June 26, 2006
Health Authority: Taiwan: Department of Health

Keywords provided by China Medical University Hospital:
Respiratory distress syndrome (RDS)
Premature infants
Chronic lung disease (CLD)
Bronchoalveolar lavage fluid (BALF)
Cytokines

Additional relevant MeSH terms:
Syndrome
Lung Diseases
Respiratory Distress Syndrome, Newborn
Disease
Pathologic Processes
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Budesonide
Pulmonary Surfactants
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 18, 2014