PDA Treatment With Ibuprofen and Changes in Tissue Oxygenation.

Study Overview
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Brief Summary
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Babies who are born very prematurely are often born with murmurs in the heart. In preterm babies, one of the most common causes of murmur is the presence of a PDA. This is the persistence of a connection that normally exists in the baby before it is born, connecting between the major blood vessels that leave the heart. In term babies, this channel closes shortly after birth when normal adult circulation is achieved. However, in preterm babies, the PDA can remain open, which can lead to multiple problems in the baby. Our current standard of treatment in the Neonatal Intensive Care Unit (NICU) is to perform cardiac ultrasound (echocardiogram) in all babies less than 29 weeks gestation to diagnose the presence of hsPDA. We also use an echocardiogram to follow the PDA until complete closure. If present, the standard treatment in the NICU is to give medication, usually Ibuprofen, a non-steroidal anti-inflammatory drugs (NSAID), to close the PDA. Near-infrared spectroscopy (NIRS) is a new type of device to detect oxygenated blood supply to the brain, kidney, and abdominal regions. This device is used to assess the effects of Ibuprofen on oxygen supply to these three regions.

Official Title
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A Pilot, Randomized Controlled Study of the Effects of High Dose Ibuprofen on Cerebral and Splanchnic Tissue Oxygenation During Treatment of Hemodynamically Significant Patent Ductus Arteriosus (hsPDA) in Preterm Infants

Conditions
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Patent Ductus Arteriosus After Premature Birth

Intervention / Treatment
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* Drug: Standard Dose Ibuprofen
* Drug: High Dose Ibuprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants less than (< )29 weeks gestation at birth Echocardiographic evidence of hsPDA (as outlined in the NICU PDA treatment guidelines) at 7-21 days of life requiring pharmacologic treatment as determined by the managing physician. Exclusion Criteria: Preterm infants with congenital heart disease except for PDA, PFO (patent foramen ovale), small and restrictive ASD (atrial septal defect), or small VSD (ventricular septal defect). Preterm infants with lethal genetic malformations. Preterm infants with congenital abdominal wall defects (omphalocele, gastroschisis). Preterm infants with congenital or acquired brain anomaly. Preterm infants with contraindications to Ibuprofen therapy, including severe intraventricular hemorrhage (IVH), low platelet count < 50,000 platelets per microliter, renal impairment with creatinine >160 mmol/L or necrotizing enterocolitis (NEC) > Stage 2 (using modified bell's Criteria). Preterm infants with spontaneous intestinal perforation (SIP). Acute kidney injury (defined as an increase in serum creatinine of 50% or more from the previous lowest value or a urinary output of less than 1 mL/kg per hr.).

Ages Eligible for Study
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Maximum Age: 29 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: The investigators are equipped with unique and complementary expertise that will propel this promising work forward. We will recruit 30 preterm infants less than (<)29 weeks gestation at birth with echocardiographic evidence of hsPDA that require pharmacologic treatment. We will examine renal, cerebral, intestinal blood flow and tissue oxygenation in high-risk preterm infants receiving high dose or standard-dose Ibuprofen treatment for hsPDA. Successful completion of this study will establish feasibility and provide proof-of-concept for a future multi-center trial. We will use descriptive statistics to compare patients' characteristics. To compare NIRS and Doppler data between the two groups, we will use paired t-test if data is normally distributed or Wilcoxon signed-rank test if not normally distributed
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 infants<br>(n=15) will receive three doses of standard-dose Ibuprofen. (10-5-5 mg/kg) 1 dose every 24 hours after enrollment, for a total of 3 doses | Drug: Standard Dose Ibuprofen<br>* (10-5-5 mg/kg) 1 dose every 24 hours after enrollment, for a total of 3 doses<br>|
| Active Comparator: Group 2 infants<br>(n = 15) will receive three doses of high-dose Ibuprofen Motrin. (20-10-10 mg/kg) 1 dose every 24 hours after enrollment, for a total of 3 doses | Drug: High Dose Ibuprofen<br>* (20-10-10 mg/kg) 1 dose every 24 hours after enrollment, for a total of 3 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in regional tissue oxygenation (splanchnic, cerebral, and the splanchnic-cerebral oxygenation ratio 'SCOR') during hsPDA treatment |  | with the first 28 days after enrolment | 
| Change in splanchnic, cerebral, and renal Doppler blood flow during hsPDA treatment [Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), and Resistive Index (RI)] |  | with the first 28 days after enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Necrotizing Enterocolitis (NEC): > 2 (Modified bell's Criteria) |  | with the first 28 days after enrolment | 
| Spontaneous intestinal perforation (SIP) |  | with the first 28 days after enrolment | 
| Incidence of oliguria |  | (<1 ml/kg/hour for > 12 hours) | 
| Feeding intolerance | we define feeding intolerance as the decision by the managing team to withhold feeds for at least 24 hours in the absence of definite evidence of medical or surgical NEC | with the first 28 days after enrolment | 
| Gastrointestinal bleeding | Any amount of visible bright red or altered blood in emesis, nasogastric tube, or feces | with the first 28 days after enrolment | 
| Pulmonary hemorrhage |  | with the first 28 days after enrolment | 
| Presence of echocardiographic features of pulmonary hypertension |  | with the first 28 days after enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ibuprofen