PDA Treatment With Ibuprofen and Changes in Tissue Oxygenation.

NCT05325177 | Unknown Phase 4 DMC

• 1 other identifier: NICU-PDA-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Patent Ductus Arteriosus After Premature Birth

Keywords

Ibuprofen

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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

  with the first 28 days after enrolment

• Gastrointestinal bleeding

  with the first 28 days after enrolment

Study Arms (2)

Group 1 infants

ACTIVE COMPARATOR

(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

Group 2 infants

ACTIVE COMPARATOR

(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

Interventions

Standard Dose Ibuprofen DRUG

(10-5-5 mg/kg) 1 dose every 24 hours after enrollment, for a total of 3 doses

Group 1 infants

High Dose Ibuprofen DRUG

(20-10-10 mg/kg) 1 dose every 24 hours after enrollment, for a total of 3 doses

Group 2 infants

Eligibility Criteria

• Age: Up to 29 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.).

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa General Hospital

Ottawa, Canada

RECRUITING

MeSH Terms

Interventions

Ibuprofen

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Central Study Contacts

Nadya Ben Fadel, MD

CONTACT

613-737-7600; nbenfadel@cheo.on.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 13, 2022
• Study Start: June 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 31, 2024
• Last Updated: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)