Comparing Ibuprofen And Indomethacin For The Treatment Of The Patent Ductus Arteriosus in Very Premature Babies
Summary
The purpose of the study is to determine the safety and efficacy of ibuprofen, compared with indomethacin, in the treatment for the closure of the patent ductus arteriosus in premature babies born under 29 weeks gestation
Description
According to Very Low Birth Weight (VLBW) High Risk Registration database in KKWCH, a hemodynamically significant patent ductus arteriosus (PDA) is a common problem in very premature infants born at a gestational age of 29 weeks and under, with more than 50% of them needing indomethacin treatment for closure of the PDA.
Prostaglandins play a major role in keeping the ductus patent . Indomethacin, because of its anti-prostaglandin effect via inhibition of the prostaglandin forming cyclo-oxygenase enzymes, has been used to medically close the PDA since the 1970s. Concerns with this drug relate to its effect on cerebral, renal and gastrointestinal blood flow. Necrotising enterocolitis (NEC), gastrointestinal perforation, gastrointestinal bleeding, transient or permanent renal impairment and reduced cerebral blood flow have been associated with indomethacin.
Ibuprofen treatment for PDA have been reported in the 1990s. It is as effective as indomethacin in closing the PDA. It is potentially better than indomethacin because regional blood flows were not affected. The few trials that have been done comparing intravenous ibuprofen and indomethacin involved mainly heavier very low birth weight (VLBW) infants. In a New England Journal of Medicine editorial on this subject, Clyman pointed out the need for trials involving the very immature infants to look at efficacy and safety.
The main obstacle for ibuprofen use in premature infants is the absence of a commercially available intravenous preparation. In our proposed trial a new i.v. ibuprofen preparation manufactured by Cumberland Pharmaceuticals (Nashville, Tennessee) will be used.
A Cochrane systematic review on ibuprofen for the treatment of PDA in premature infants concluded that it performed with the same effectiveness when compared to indomethacin. There was a significant decrease in the incidence of oliguria in the ibuprofen arm, with a higher risk of chronic lung disease at 28 days of life (borderline statistical significance), but not at 36 weeks.There is no biologically plausible explanation for the latter effect and this could be attributed to chance in view of this, plus the weak statistical proof. The other problem with this review was that it included trials where enteral ibuprofen was used, and this route is clearly impractical in the very premature infants which we plan to study because of the unpredictable absorption from the immature gut and their general intolerance to feeding at such an early age. The concern regarding pulmonary hypertension with the prophylactic use of ibuprofen also should not apply to our planned study where the time of administration of the drugs will be around 24 hours of age.
The potential benefits stemming from ibuprofen's biological advantage over indomethacin will be reduction in the rates of oliguria, gastrointestinal bleeding, NEC and gastrointestinal perforation. NEC and gastrointestinal perforation are conditions with serious morbidities and usually result in prolonged hospital stay and poorer neurodevelopmental outcome for the affected infants. A better drug could lead to cost savings.
Neurosensory impairment is an important outcome to monitor because indomethacin reduces cerebral blood flow. This point was also emphasized in the Cochrane systematic review mentioned above. However this will be the subject of another proposal in view of the significant additional budget needed.
The objective of the trial is to compare, the the safety and efficacy of intravenous ibuprofen treatment for the closure of the patent ductus arteriosus diagnosed via 2D echocardiography in very premature babies born under 29 weeks of gestation, with traditional therapy indomethacin.
The primary outcome measure will be the incidence of oliguria and gastric bleeding within one week after the 1st dose of treatment
Study Design
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Ductus Arteriosus, Patent
Intervention
Ibuprofen and Indomethacin
Location
KK Women's and Children's Hospital / National University Hospital
Singapore
Singapore
229899
Status
Withdrawn
Source
KK Women's and Children's Hospital
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00470743
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Ductus Arteriosus, Patent
A congenital heart defect characterized by the persistent opening of fetal DUCTUS ARTERIOSUS that connects the PULMONARY ARTERY to the descending aorta (AORTA, DESCENDING) allowing unoxygenated blood to bypass the lung and flow to the PLACENTA. Normally, the ductus is closed shortly after birth.
Persistent Fetal Circulation Syndrome
A syndrome of persistent PULMONARY HYPERTENSION in the newborn infant (INFANT, NEWBORN) without demonstrable HEART DISEASES. This neonatal condition can be caused by severe pulmonary vasoconstriction (reactive type), hypertrophy of pulmonary arterial muscle (hypertrophic type), or abnormally developed pulmonary arterioles (hypoplastic type). The newborn patient exhibits CYANOSIS and ACIDOSIS due to the persistence of fetal circulatory pattern of right-to-left shunting of blood through a patent ductus arteriosus (DUCTUS ARTERIOSUS, PATENT) and at times a patent foramen ovale (FORAMEN OVALE, PATENT).
Ductus Arteriosus
A fetal blood vessel connecting the pulmonary artery with the descending aorta.
Hypoplastic Left Heart Syndrome
A condition caused by underdevelopment of the whole left half of the heart. It is characterized by hypoplasia of the left cardiac chambers (HEART ATRIUM; HEART VENTRICLE), the AORTA, the AORTIC VALVE, and the MITRAL VALVE. Severe symptoms appear in early infancy when DUCTUS ARTERIOSUS closes.
Truncus Arteriosus, Persistent
A congenital anomaly caused by the failed development of TRUNCUS ARTERIOSUS into separate AORTA and PULMONARY ARTERY. It is characterized by a single arterial trunk that forms the outlet for both HEART VENTRICLES and gives rise to the systemic, pulmonary, and coronary arteries. It is always accompanied by a ventricular septal defect.
Clinical Trials
Second Course of Therapy for Resistant Patent Ductus Arteriosus (PDA)
Patency of the ductus arteriosus (PDA) is functionally essential for fetal circulation, however persistence of ductal patency postnatally may have significant adverse hemodynamic effects i...
Safety/Efficacy Study of Optimizing Ibuprofen Dosing to Achieve Higher PDA Closure Rates
The purpose of this study is to determine if increasing the ibuprofen dose will increase the likelihood of closing the patent ductus arteriosus in premature babies.
Feeding During Ibuprofen or Indomethacin Treatment of Preterm Infants
We hypothesize that feeding preterm infants while they receive indomethacin or ibuprofen therapy for treatment of a patent ductus arteriosus will decrease the incidence of feeding intolera...
Ibuprofen vs. Continuous Indomethacin in the Treatment of PDA
The purpose of this study is to determine whether closure of the PDA in premature neonates using IV ibuprofen vs continuous IV indomethacin has different side effects, eg. effects on renal...
A patent ductus arteriosus (PDA) is associated with increased morbidity in premature infants. Standard indomethacin treatment is associated with intestinal and renal morbidity. B-type natr...
PubMed Articles
AIM: The aim of this study was to explore the effects of early oral ibuprofen administration on the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and define the association...
Patent ductus arteriosus (PDA) is the most common cardiovascular abnormality of the preterm infant usually treated with ibuprofen (IBU). PDA is strictly related to oxidative stress (OS) in neonates. T...
Current evidence on the safety profile of NSAIDs for the treatment of PDA.
Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants. Nonsteroidal anti-inflammatory drugs, especially Indomethacin and Ibuprofen, have been widely used for both preventio...
Estimation of patent ductus arteriosus diameters by colour Doppler echocardiography in children.
OBJECTIVE: To investigate whether accurate estimation of the diameter of the patent ductus arteriosus can be obtained by colour Doppler echocardiography. METHODS: The minimum and maximum diameters of...
Doppler manifestations of ductal steal: role in decision making.
Patent ductus arteriosus in extremely premature babies is associated with major neonatal morbidities such as necrotizing enterocolitis and intraventricular haemorrhage. Altered systemic blood flow and...
