PDA Treatment With Ibuprofen and Changes in Tissue Oxygenation.

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

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.

Study Overview

• Status: Recruiting
• Conditions: Patent Ductus Arteriosus After Premature Birth
• Intervention / Treatment: Drug: Standard Dose Ibuprofen; Drug: High Dose Ibuprofen

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nadya Ben Fadel, MD; Phone Number: 3716 613-737-7600; Email: nbenfadel@cheo.on.ca

Study Locations

• Canada
  • Ottawa, Canada
    • Recruiting
    • The Ottawa General Hospital
    • Contact: Rebecca Grimwood; Email: RGrimwood@cheo.on.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No

Description

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.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 infants; (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; (10-5-5 mg/kg) 1 dose every 24 hours after enrollment, for a total of 3 doses
Active Comparator: Group 2 infants; (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; (20-10-10 mg/kg) 1 dose every 24 hours after enrollment, for a total of 3 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Ibuprofen
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Heart Defects, Congenital; Cardiovascular Abnormalities; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Ductus Arteriosus, Patent; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: NICU-PDA-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No