Comparing Ibuprofen And Indomethacin For The Treatment Of The Patent Ductus Arteriosus in Very Premature Babies
|First Received Date ICMJE||May 7, 2007|
|Last Updated Date||June 23, 2009|
|Start Date ICMJE||May 2007|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Incidence of oliguria and gastric bleeding [ Time Frame: within one week of treatment ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00470743 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Comparing Ibuprofen And Indomethacin For The Treatment Of The Patent Ductus Arteriosus in Very Premature Babies|
|Official Title ICMJE||A Randomised Controlled Trial Comparing Ibuprofen And Indomethacin For The Treatment Of The Patent Ductus Arteriosus In Very Premature Infants|
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
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 Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Ibuprofen and Indomethacin|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Estimated Enrollment ICMJE||150|
|Estimated Completion Date||June 2009|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||up to 29 Weeks|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Singapore|
|NCT Number ICMJE||NCT00470743|
|Other Study ID Numbers ICMJE||SQPDA02|
|Has Data Monitoring Committee||No|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||KK Women's and Children's Hospital|
|Information Provided By||KK Women's and Children's Hospital|
|Verification Date||June 2009|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP