Cytokine Change in Bronchoalveolar Lavage Fluid After Early Budesonide-Surfactant Treatment in Premature Infants
Information source: China Medical University Hospital
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Premature Infants; Respiratory Distress Syndrome; Chronic Lung Disease; Bronchoalveolar Lavage Fluid; Cytokines
Intervention: Budesonide-Surfactant (Drug)
Phase: Phase 4
Status: Terminated
Sponsored by: China Medical University Hospital Official(s) and/or principal investigator(s):
Tsu-Fuh Yeh, MD, Principal Investigator, Affiliation: China Medical University Hospital
Summary
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).
Clinical Details
Study design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: 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: The secondary outcome is the clinical endpoint of survival free of oxygen dependence at 36 wks postmenstrual age.
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
Minimum age: N/A.
Maximum age: 1 Day.
Gender(s): Both.
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.
Locations and Contacts
China Medical University Hospital, Taichung, Taiwan
Additional Information
Starting date: August 2004
Last updated: June 26, 2006
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