Timing of Surgical PDA Ligation and Neonatal Outcomes

Patent Ductus Arteriosus Clinical Trial

Official title:

Effect of the Timing of Surgical PDA Ligation on Neonatal Outcomes: a Bicentric Retrospective Observational Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04126512
• Other study ID #: PDA-lig-SO-CAM
• Status: Completed
• Start date: September 25, 2019
• Est. completion date: December 31, 2019

Study information

• Verified date: June 2020
• Source: Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Patent ductus arteriosus (PDA) is common among very preterm infants. If pharmacological closure is ineffective or contraindicated, surgical ligation may be required. Access to cardiothoracic surgery may influence the timing of ligation, with possible long-term clinical effects. This study protocol aims to assess the impact of different surgical management of PDA (bedside surgery vs. referral to a cardiac surgery centre) on ligation timing and neonatal clinical outcomes in two tertiary Neonatal Intensive Care Units.

Infants born at St. Orsola-Malpighi University Hospital, Bologna, Italy (group 1, bedside ligation) and Cambridge University Hospital, Cambridge, UK (group 2, referred to an off-site specialist paediatric cardiac surgical centre) who underwent PDA ligation between 2007 and 2018 will be included in this retrospective cohort study if fulfilling the following criteria: gestational age (GA) <32 weeks, birth weight (BW) <1500 g, inborn, absence of major malformation or congenital heart disease. Neonatal clinical outcomes will be collected and compared between the 2 groups.

Description:

Patent ductus arteriosus (PDA) is a common condition among preterm infants, with an estimated incidence of 60% in extremely low birth weight infants (ELBW). Several factors, such as the relative oxygen hyposensitivity and increased sensitivity to prostaglandins of the immature tissues and the scarceness of ductal medial muscles, contribute to the patency of arterial duct in prematurely born neonates; as a consequence, the rate of spontaneous closure is inversely related to gestational age (GA) Over the past two decades, the persistence of a significant systemic-to-pulmonary shunt through the PDA has been associated with a higher incidence of adverse clinical outcomes, including acute pulmonary morbidities and bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), feeding intolerance and increased mortality rates.

The management of PDA in very preterm infants first includes supportive therapy (e.g., restricted fluid intake, diuretics, increasing end-expiratory pressure) and targeted pharmacologic treatment with cyclooxygenase inhibitors (i.e., ibuprofen, indomethacin, acetaminophen) or paracetamol if spontaneous closure does not occur. However, when pharmacological closure is ineffective or contraindicated and the neonate requires extensive respiratory support, surgical ligation may be required. PDA ligation can be performed on-site, either at the infants' bedside or in the operation room, or off-site, if a paediatric cardiac surgery team is not available locally. By favouring one approach over the other, the setting may also contribute to influence the timing for PDA ligation. To date, literature comparing the effects of early vs. delayed PDA ligation on the main neonatal morbidities has led to contrasting results; hence, the optimal timing of surgical PDA closure remains a matter of debate among neonatologists.

This study aims to assess whether a different management of surgical PDA closure (on-site bedside ligation vs. referral to an off-site specialist paediatric cardiac surgical centre) may influence the timing of the intervention and the main neurological, respiratory and gastrointestinal clinical outcomes in very low birth weight (VLBW) preterm infants from two tertiary Neonatal Intensive Care Units with different paediatric cardiac surgery capabilities. Postoperative complications, mortality rates and the length of hospital stay will be also evaluated as secondary outcomes.

Methods Preterm infants <32 weeks' gestation born at the Neonatal Intensive Care Unit (NICU) of Cambridge University Hospital (CUH, Cambridge, UK) and of St. Orsola-Malpighi Hospital (SOM, Bologna, Italy) between January 1st, 2007 and June 30th, 2018 will be included in this retrospective study if, due to failed or contraindicated medical therapy, underwent surgical closure of PDA, judged hemodynamically significant (hsPDA) either on a clinical (hypotension, ventilator dependence, heart failure symptoms) or echocardiographic basis (left atrial/aortic root ratio >1.5, pulsatile left-to-right shunt and/or mean velocity in the left pulmonary artery >0.6 m/s). The presence of major congenital malformations, including congenital heart disease, was considered an exclusion criterion.

Echo-Doppler studies of each patient will be reviewed, and the following parameters from the latest pre-operative scan were will be recorded: PDA size and shunt characteristics (direction and pattern); left atrial to aortic root ratio; evidence of reversed end-diastolic flow in the descending aorta and/or in the middle or anterior cerebral artery (when evaluated). Contraindications and adverse effects of pharmacological treatment will be also reviewed. Failure of pharmacological treatment is defined by PDA persistency after at least two full pharmacological courses.

Neonatal characteristics and the following pre- and peri-operative data will be recorded:

echocardiographic PDA characteristics, PDA management (supportive or pharmacological treatment, related adverse effects, rates of responsiveness and recurrence), post-conceptional age, days of life and weight at surgical intervention.

Neonatal outcomes include mortality rates, IVH, periventricular leukomalacia (PVL), NEC, sepsis (defined as relevant symptoms with positive blood culture and/or C reactive protein >25 mg/L and >5 days of antibiotic treatment), retinopathy of prematurity (ROP, any grade) and BPD (defined as any requirement for supplemental oxygen and/or positive-pressure respiratory support at 36 weeks' post-conceptional age). Length of hospital stay, time needed to achieve full enteral feeding, total duration of mechanical ventilation and the rate of supplemental oxygen need at hospital discharge will be also evaluated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Gender: All
• Age group: N/A to 6 Months

Eligibility

Inclusion Criteria:

• Gestational age <32 weeks' gestation

• Surgical PDA ligation

Exclusion Criteria:

• Major congenital malformations

• Congenital heart disease

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent
• Patent Ductus Arteriosus
• Patent Ductus Arteriosus - Delayed Closure
• Patent Ductus Arteriosus After Premature Birth
• Premature Birth

Intervention

Other:
• PDA ligation
PDA ligation was performed at bedside, if a local cardiac surgery team was available, or in the case this service was not available, infants were referred to off-site specialist paediatric cardiac surgical services, where PDA ligation was performed.

Locations

Country	Name	City	State
Italy	S. Orsola-Malpighi University Hospital	Bologna	Emilia-Romagna
United Kingdom	The Rosie Hospital, Cambridge University Hospitals	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi

Countries where clinical trial is conducted

Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PDA ligation timing	Days of life at PDA ligation in SOM group compared to the CUH group	From birth up to hospital discharge (average period: 6 months)
Primary	Mortality	Any decrease in the mortality rate in the SOM group compared to the CUH group	From birth up to hospital discharge (average period: 6 months)
Primary	Bronchopulmonary dysplasia	Any decrease in the rate of bronchopulmonary dysplasia in the SOM group compared to the CUH group	36 weeks' post-conceptional age
Secondary	Intraventricular haemorrhage (IVH)	Any decrease in the incidence of IVH in SOM group compared to the CUH group	From birth up to hospital discharge (average period: 6 months)
Secondary	Periventricular leukomalacia (PVL)	Any decrease in the incidence of PVL in SOM group compared to the CUH group	From birth up to hospital discharge (average period: 6 months)
Secondary	Necrotizing enterocolitis (NEC)	Any decrease in the incidence of NEC in SOM group compared to the CUH group	From birth up to hospital discharge (average period: 6 months)
Secondary	Retinopathy of prematurity (ROP)	Any decrease in the incidence of ROP in SOM group compared to the CUH group	From birth up to hospital discharge (average period: 6 months)
Secondary	Oxygen need at discharge	Any decrease in the rate of oxygen need at discharge in SOM group compared to the CUH group	Hospital discharge (average age: 6 months of life)
Secondary	Length of hospital stay	Duration of hospitalization in the SOM group compared to the CUH group	Hospital discharge (average age: 6 months of life)
Secondary	Time to achieve full enteral feeding	Time needed to achieve full enteral feeding in the SOM group compared to the CUH group	From birth up to hospital discharge (average period: 6 months)
Secondary	Duration of mechanical ventilation	Days spent on mechanical ventilation in the SOM group compared to the CUH group	From birth up to hospital discharge (average period: 6 months)