The Best Treatment Strategy: Surgical vs Pharmacological to Close the Ductus Arteriosus Persistent in Preterm Infants

Study Overview
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Brief Summary
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The decision to treat patent ductus arteriosus in preterm infants, varies from a conservative, medical or immediate surgical treatment; although, at present, there is some controversy about this decision. This study aims to determine the efficacy and safety of surgical versus pharmacological treatment of patent ductus arteriosus in preterm infants.

Detailed Description
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The ductus arteriosus varies in length, diameter and morphology. The duct closure occurs in two stages: the first one or functional closure; the second or anatomical closure. This condition is associated with other heart diseases, which modify the natural history and require individualized treatment. Treatment varies from conservative, pharmacological or surgical treatment, and there are many controversies regarding the treatment decision. And aims of the closure, is to decrease the likelihood of irreversible pulmonary vascular disease, reduce associated morbidity and mortality. The role of prostaglandin E2 is the permeability of the conduit, by which is indicated the use of cyclooxygenase inhibitors for closure (indomethacin and ibuprofen). In various research studies many factors associated with failure of pharmacological treatment (gestational age, antenatal indomethacin less than 48 hours before delivery, use of high frequency ventilation) are reported, therefore, there is an alternative treatment which is surgical closure. In the pharmacological treatment of ductus arteriosus persistent it should be individualized according to gestational age, respiratory condition and size of the newborn. With early drug treatment can achieve closure of patent ductus arteriosus in up to 90% of cases, while the late treatment between 50-65%. However, it is reported that after treatment with indomethacin, reopening occurs, two doses are recommended more after the first, in addition to its side effects, contraindications and complications. As well, ibuprofen contraindications. So the closure of the ductus arteriosus persistent may be performed by hemodynamics and surgical closure (standard left thoracotomy or thoracoscopic technique). There are specific indications for surgical treatment (no response to two cycles of medical treatment in newborns with less than 1000 gr weight in which I fail one indomethacin, absolute contraindications to it, with significant hemodynamic repercussions. With surgical treatment before the third week of life minimizing morbidity. it is reported by many authors that complications are rare and mortality is associated with other complications of prematurity. So Surgical treatment is considered as an alternative because of its low incidence of complications, mortality and lower cost, plus a total occlusion between 94-100% Because of this, the treatment of patent ductus arteriosus in preterm infants, ranging from conservative treatment, medical or surgical, and currently there is much controversy in the treatment decision. This study aims to determine the efficacy and safety of surgical versus pharmacological treatment for the permanent closure of the patent ductus arteriosus in preterm infants. Methods: Is open label randomized controlled the clinical trial with: 1) experimental group assigned to surgical treatment; 2) control group assigned to pharmacological treatment, for closure of patent ductus arteriosus.

Official Title
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The Best Treatment Strategy: Surgical Versus Pharmacological, to Close the Ductus Arteriosus Persistent in Preterm Infants. A Randomized Controlled Trial

Conditions
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Persistent Ductus Arteriosus

Intervention / Treatment
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* Procedure: Surgical treatment
* Drug: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants Preterm infants hospitalized in the Neonatal Intensive Care Unit with a diagnosis of patent ductus arteriosus Exclusion Criteria: Preterm infants with supportive treatment and / or drug prior to patent ductus arteriosus in another medical unit Preterm infants diagnosed with heart disease associated complex. Preterm infants with associated disease (not hemodynamic or cardiovascular) and its impact on his state of health prior to drug treatment and / or surgery Preterm infants with contraindications to pharmacological and / or surgery treatment Newborns diagnosed with patent ductus arteriosus but with incomplete medical records

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 30 Days

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgical treatment<br>Implement surgical treatment for closure of patent ductus arteriosus | Procedure: Surgical treatment<br>* Standard left thoracotomy<br>* Other names: Surgery;|
| Active Comparator: Control group<br>- Indomethacin: Administer 1 full cycle (3 doses) of indomethacin (1 dose every 12 hours) for 2 days Dose 0.1 - 0.25 mg / kg - Ibuprofen: Administer 1 full cycle (3 doses) of ibuprofen (1 dose every 24 hours) for 2 days Dose 05 - 10 mg / kg - Acetaminophen: Administer 1 full cycle (12 doses) of acetaminophen (1 dose every 6 hours) for 3 days Dose 15 mg / kg | Drug: Control group<br>* - Indomethacin: Administer 1 full cycle (3 doses) / (1 dose every 12 hours) in the first fourteen days of life: Preterm infants less than 48 hours of life: first dose 0.2 mg/kg, second dose 0.1 mg/kg and third dose 0.1 mg/kg Preterm infants more than 48 hours of life: first dose 0.2 mg/kg, second dose 0.2 mg/kg and third dose 0.2 mg/kg And preterm infants more than 7 days of life: first dose 0.2 mg/kg, second dose 0.25 mg/kg and third dose 0.25 mg/kg - Ibuprofen: Administer 1 full cycle (3 doses) / (1 dose every 24 hours) in the first fourteen days of life of preterm infants: First dose 10 mg/kg Second dose 05 mg/kg Third dose 05 mg/kg - Acetaminophen Administer 1 full cycle, in the first fourteen days of life in preterm infants: Acetaminophen 15 mg/kg every 6 hours for 3 days<br>* Other names: Pharmacological;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate of closure patent ductus arteriosus | Tracking each patient for 10 days after treatment (surgical / pharmacological) to verify success rate of closure of patent ductus arteriosus (Failure of ductal closure ) (%) | 10 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from diagnosis to resolution of patent ductus arteriosus | To compare the time from diagnosis to resolution of patent ductus arteriosus (days) | 1 month | 
| Time from start of treatment until resolution | To compare the time from start of treatment until resolution of patent ductus arteriosus (days) | 10 days after treatment | 
| Time limitation of family contact | To compare the time limitation of family contact from diagnosis to hospital discharge of newborns of patent ductus arteriosus (days) | 1 month | 
| Adverse effects and complications of treatment | Describe the type of adverse effects and / or complications (Chronic lung disease , Intraventricular haemorrhage, Creatinine level > 1.8 mg/dl, Pneumothorax , Sepsis, Necrotising enterocolitis, Retinopathy of prematurity, Other bleeding) and the frequency of the two study groups (yes / no) | 10 days | 
| Death before discharge | To compare related mortality among surgical and pharmacological treatment (%) | 1 month | 
| Time of mechanical ventilatory support, parenteral nutrition, fasting, supplementary O2 | To compare the duration of mechanical ventilatory support, parenteral nutrition, fasting, supplementary O2 (days). | 1 month | 
| Anatomy of the ductus arteriosus persistent | Describe the size of the ductus arteriosus (mm) | 1 month | 
| Gestational age at birth | Describe the gestational age of neonates (weeks) | At birth | 
| Apgar | Describe the Apgar score of newborns (3-9) | At birth | 
| Blood flow | Describe the direction of blood flow of the ductus arteriosus (left-right, left-right, two-way) | 1 month | 
| Gradient of the ductus arteriosus | Describe the gradient of the ductus arteriosus (mmHg). | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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persistent ductus arteriosus, preterm infants, surgical treatment, pharmacological treatment