PDA Clinical Trial
Official title:
Comparison of Oral and Intravenous Ibuprofen for Treatment of Patent Ductus Arteriosus in Extremely Premature Infants: A Randomized Controlled Trial
Background:
Patent ductus arteriosus (PDA) continues to be one of the most common problems in premature
infants. Pharmacological closure of PDA with intravenous (IV) indomethacin was first
reported in 1976, however, concern remains regarding the safety of indomethacin, which
affects renal, GI and cerebral perfusion and may lead to complications such as transient or
permanent renal dysfunction, NEC, GI hemorrhage, and reduced cerebral oxygenation. Recently,
IV ibuprofen has been shown to be effective for the closure of patent ductus arteriosus in
premature infants, without reducing mesenteric, renal, or cerebral blood flow. We have
developed the echocardiographic PDA flow pattern as a guide for PDA treatment, fewer doses
of drugs were needed to achieve acceptable closing rates. We have also reported that IV
ibuprofen is as effective as IV indometacin for the PDA treatment in extremely premature
infants, without increasing the incidence of complications in a randomised controlled trial.
Several studies reported that oral ibuprofen may be effective for PDA treatment. To date
there is no firm conclusion as to the efficacy and safety of oral ibuprofen compared with IV
ibuprofen for PDA closure in extremely premature infants.
Objective:
Since the efficacy of pharmacological closure of PDA is related to gestational age, and
extremely premature infants carry the highest rate of mortality and morbidity. We intend to
conduct a randomized controlled trial to compare oral and intravenous ibuprofen for
treatment of PDA in this high-risk population of extremely premature infants.
Methods:
Extremely premature infants (gestational age < 28 weeks) admit to the NICU will be eligible
for enrollment. Informed parental consent will be obtained according to the Institutional
Review Board's instructions. Extremely premature infants with respiratory distress syndrome
(RDS) and PDA confirmed by echocardiography will be randomly assigned to receive either oral
or IV ibuprofen. The subsequent doses of ibuprofen are also determined according to our
specific echocardiographic PDA flow patterns at intervals of once every 24 hours from the
last dose. The dosage of oral or ibuprofen is 10 mg/kg (1 ml) and then 5 mg/kg at 24-hour
intervals as indicated by echocardiographic PDA flow pattern.
Sample Size Calculation and Length of the Study Period:
About 50-60 extremely premature infants will be admitted to our NICU each year. To prove
with McNemar's Test at a one-sided significance level of 5% and a power of 90% that using
oral ibuprofen instead of IV ibuprofen results in comparable PDA closure rates, only 31
extremely premature infants with RDS and PDA have to be enrolled. Allowing for attrition and
exclusion from the final study groups, the length of the study period will be safe to set to
2 years.
Expected Results:
We expect to determine whether oral ibuprofen is effective and safe in inducing PDA closure
in extremely premature infants and to compare the complications between infants treated with
oral ibuprofen and those with IV ibuprofen.
| Status | Recruiting |
| Enrollment | 70 |
| Est. completion date | June 2012 |
| Est. primary completion date | June 2012 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | N/A to 24 Hours |
| Eligibility |
Inclusion Criteria: - premature infants gestational age < 28 weeks, respiratory distress syndrome requiring assisted ventilation, a PDA without other cardiac anomalies confirmed by echocardiography within 24 hours after birth, Exclusion Criteria: - severe congenital anomalies or lethal cardiopulmonary conditions, and informed consent could be obtained from parents |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Taiwan | China Medical University Hospital | Taichung |
| Lead Sponsor | Collaborator |
|---|---|
| China Medical University Hospital |
Taiwan,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The primary outcome is to ascertain whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants. | Number of extremely premature infants with PDA closed or Adverse Events as a Measure of efficiency and safety. | 1 month | Yes |
| Secondary | A secondary objective is to compare the complications between infants treated with oral ibuprofen and those treated with IV ibuprofen. | Number of extremely premature infants in each group with PDA closed or Adverse Events as a Measure of efficiency and safety. | 1 month | Yes |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02396004 -
NIRS in PDA VLBW Infants
|
N/A | |
| Completed |
NCT05321849 -
Echocardiography-guided Percutaneous Patent Ductus Arteriosus Closure
|
||
| Completed |
NCT04379843 -
The Efficacy of Implementing a Treatment Algorithm in Managing Patent Ductus Arteriosus (PDA) in the Extremely Low Birth Weight Neonatal Population.
|
||
| Completed |
NCT01755728 -
Paracetamol (Acetaminophen) for Closure of PDA in Preterm Infants
|
Phase 3 |