Clinical trial NCT05325177: PDA Treatment With Ibuprofen and Changes in Tissue Oxygenation.
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Patent Ductus Arteriosus After Premature Birth
Keywords: Ibuprofen
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2022-04-13
Enrollment: 30
Sex: ALL
Maximum age (years): 29
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention 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
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

* Not able to consent for any reason
* 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.
* Infants who receive ibuprofen for PDA treatment during the first week of life will be excluded. We will recruit infants between day 7 and 21 only because high-dose ibuprofen is not indicated during the first week of life
* 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.).

Primary outcomes:
measure: Change in regional tissue oxygenation (splanchnic, cerebral, and the splanchnic-cerebral oxygenation ratio 'SCOR') during hsPDA treatment
timeFrame: with the first 28 days after enrolment
measure: Change in splanchnic, cerebral, and renal Doppler blood flow during hsPDA treatment [Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), and Resistive Index (RI)]
timeFrame: with the first 28 days after enrolment
Secondary outcomes:
measure: Necrotizing Enterocolitis (NEC): > 2 (Modified bell's Criteria)
timeFrame: with the first 28 days after enrolment
measure: Spontaneous intestinal perforation (SIP)
timeFrame: with the first 28 days after enrolment
measure: Incidence of oliguria
timeFrame: (<1 ml/kg/hour for > 12 hours)
measure: Feeding intolerance
timeFrame: with the first 28 days after enrolment
measure: Gastrointestinal bleeding
timeFrame: with the first 28 days after enrolment
measure: Pulmonary hemorrhage
timeFrame: with the first 28 days after enrolment
measure: Presence of echocardiographic features of pulmonary hypertension
timeFrame: with the first 28 days after enrolment
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa General Hospital
Study officials:
References: