Clinical Research Directory

Early Prediction of Spontaneous Patent Ductus Arteriosus (PDA) Closure and PDA-Associated Outcomes

Patent ductus arteriosus (PDA), very common in preterm infants, is the delayed closure of a fetal blood vessel that limits blood flow through the lungs. PDA is associated with mortality and harmful long term outcomes including chronic lung disease and neurodevelopmental delay. Although, treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve important outcomes. Left untreated, most PDAs close spontaneously. Thus, PDA treatment is increasingly controversial and varies markedly between hospitals and individual providers. The relevant and still unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat and when. Treatment detriments may outweigh benefits, since all forms of deliberate PDA closure have potential adverse effects, especially in infants destined for early, spontaneous PDA closure. Unfortunately, clinicians cannot currently predict in the 1st month which infants are at highest risk for persistent PDA, and which combination of clinical risk factors, echocardiographic (echo) measurements, and serum biomarkers may best predict PDA-associated harm. The American Academy of Pediatrics has acknowledged early identification of infants at high-risk from PDA as a key research goal for informing future PDA-treatment effectiveness trials. Our objective is to use a prospective cohort of untreated infants with PDA to predict spontaneous ductal closure timing and identify echo measurements and biomarkers that are present in the 1st postnatal month and associated with long-term impairment. Our central hypothesis is that these risk factors can be determined to inform appropriate clinical treatments when necessary. Clinical, serum and urine biomarkers (BNP, NTpBNP, NGAL, H-FABP), and echo variables sequentially collected during each of the first 4 postnatal weeks will be examined. In addition myocardial deformation imaging (MDI) and tissue Doppler imaging (TDI), innovative echo methods, will facilitate the quantitative evaluation of myocardial performance. Aim 1 will estimate the probability of spontaneous PDA closure and predict the timing of ductal closure using echo, biomarker, and clinical predictors. Aim 2 will specify which echo predictors and biomarkers are associated with mortality and severity of respiratory illness at 36-weeks PMA. Aim 3 will identify which echo predictors and biomarkers are associated with 22- to 26-month neurodevelopment. All models will be validated in a separate cohort. This project will significantly contribute to clinical outcomes and PDA management by reducing unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure, and will permit the development of outcomes-focused trials to examine the effectiveness of PDA closure in those "high-risk" infants most likely to receive benefit.

PDA for Kidneys Study

The goal of this observational study is to gather more information on kidney oxygen levels in babies with a patent ductus arteriosus (PDA), and evaluate the relationships between kidney oxygen levels, PDA status and kidney injury. Researchers will do this by looking at ultrasound images of the heart, analyzing substances in the urine, and evaluating oxygen levels in the kidneys.

Post Marketing Clinical Follow Up Study to Evaluate Efficacy and Safety of the Occlutech PDA Occluder in Patients With Patent Ductus Arteriosus Defects

This retrospective and prospective, multicenter, international post marketing follow up study evaluates the safety and efficacy of the Occlutech® PDA Occluder, delivered using the Occlutech Occlusions Pusher (OOP), in subjects with patent ductus arteriosus (PDA) defects. Safety and efficacy assessments include vital signs, electrocardiograms, and echocardiographic evaluations performed at baseline/implantation (including assessments within 36 hours post procedure), as well as at follow up visits occurring between Day 30 and Day 90, 6 months to 1 year, 1 to 2 years, and 2 to 3 years after implantation.

Amplatzer Piccolo Occluder Japan Post-marketing Database Surveillance

The purpose of this post-marketing clinical use database surveillance is to observe the frequency, type, and degree of adverse device effects and adverse events in order to assure the safety of the medical device, and to collect safety and efficacy information for evaluating the results of its clinical use.

Management of the PDA Trial

Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.

Precision Dosing of Oral Ibuprofen for PDA, A Pilot RCT

Newborns born early are at risk for a serious health problem called patent ductus arteriosus (PDA). PDA is a passageway between heart and lung that can cause life-threatening complications such as bleeding in the brain or even death if it remains open and large. When closure of PDA is needed, doctors make every attempt to do it as soon as possible. Ibuprofen is the best drug to close the PDA, but it only works for 50% of small newborns. The investigators have shown before that small newborns handle ibuprofen differently and the amount of active ibuprofen that reaches their blood can be very unpredictable. Studies have shown if enough ibuprofen reaches the body, it can close the PDA. Therefore the investigators designed this study to see whether it is possible to give each newborn the right amount of ibuprofen that their body needs to close the PDA. The investigators will compare two ways to give ibuprofen in a small number of newborns: 1 - standard amount of ibuprofen to everyone, which is the usual care or 2 - ibuprofen doses that will be changed based on how much active ibuprofen has reached the body and how well the newborn's PDA is closing. The investigators will then compare the number of PDAs closed in each group and closely monitor any possible challenges for this new practice. By doing this project, the goals can be summarized as below: A. Primary goal: To determine if it is feasible to successfully run a larger study in the future. B. Secondary goals 1. To assess how well and how safely the personalized (MIPD) method works, using a tool called WAPPS-PDA to guide dosing. 2. To compare the effectiveness and safety of the personalized method with standard ibuprofen dosing. 3. To identify drug levels in the blood (Cmin, AUC0-24, AUC0-72) that are associated with complete, partial, or no response to treatment.

NeoDoppler: New Ultrasound Technology for Continuous Monitoring of Cerebral Circulation Pilot

Non-invasive tools for monitoring of course of disease are important and necessary in the treatment of pre-term/premature infants and sick neonates. For many years, the ultrasound group in Trondheim has been at the forefront in the development of new ultrasound technology for the diagnosis and monitoring of disease. Several methods previously developed in this research group are today widely used in hospitals around the world. In this project the investigators aim to test a new ultrasound technology that allows continuous monitoring of cerebral blood flow in sick neonates and pre-term children. This technology was CE-certified in October 2022, and in this project the investigators will test the CE-certified version with the newest available approved software.

Improving Care for Children With Congenital Heart Disease.

Establish a cardiovascular biomarker profile to help screening for congenital heart disease in infants and children as well as use non-invasive cardiac imaging in combination with such profiling to better predict the need for future cardiac interventions such as open heart surgery or cardiac catheter intervention in selected types of with congenital heart disease.

PUFAs in Preterm Infants

The research endeavors to examine the critical composition of Polyunsaturated Fatty Acids (PUFAs) in premature infants across different gestational stages and under varying disease conditions, and delineate the metabolic attributes of PUFAs in premature infants and their interplay with the onset of diseases. This study anticipates furnishing a theoretical foundation for the rationalization of PUFAs supplementation in premature infants and for informing strategies related to disease prevention and management.