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

Persistent Ductus Arteriosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02602054
• Other study ID #: HGNAE-07
• Status: Recruiting
• Phase: Phase 2
• First received: November 8, 2015
• Last updated: November 16, 2015
• Start date: October 2015
• Est. completion date: October 2017

Study information

• Verified date: November 2015
• Source: Hospital General Naval de Alta Especialidad - Escuela Medico Naval
• Contact: Esaú Luis Nieto, Pediatrician
• Phone: 5564787736
• Email: dresauln[@]gmail.com
• Is FDA regulated: No
• Health authority: Mexico: Secretaria de Salud
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 2017
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Days

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent
• Persistent Ductus Arteriosus

Intervention

Procedure:
• Surgical treatment
Standard left thoracotomy

Drug:
• Control group
- 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

Locations

Country	Name	City	State
Mexico	Hospital General Naval de Alta Especialidad	Distrito Federal

Sponsors (1)

Lead Sponsor	Collaborator
Hospital General Naval de Alta Especialidad - Escuela Medico Naval

Country where clinical trial is conducted

Mexico, 

References & Publications (18)

Clyman RI, Chorne N. Patent ductus arteriosus: evidence for and against treatment. J Pediatr. 2007 Mar;150(3):216-9. Review. — View Citation

Elorza MD, Pérez RJ, Quero JJ. Tratamiento del Ductus Arterioso Persistente sintomático del recién nacido pretérmino. Hospital Universitario La Paz. Servicio Madrileño de Salud. 2005 (3): 1-8.

Gallardo MAF, González SJM, et al. Experiencia en el cierre quirúrgico de ducto arterioso permeable en la Unidad de Cuidados Intensivos Neonatales de un hospital de segundo nivel en Guadalajara, Jalisco, México. Bol Med Hosp Infant Mex 2010; 67: 128-32

Gimeno Navarro A, Cano Sánchez A, Fernández Gilino C, Carrasco Moreno JI, Izquierdo Macián I, Gutiérrez Laso A, Morcillo Sopena F. [Ibuprofen versus indomethacin in the treatment of patent ductus arteriosus in preterm infants]. An Pediatr (Barc). 2005 Sep — View Citation

Golombek SG, Sola A, Baquero H, Borbonet D, Cabañas F, Fajardo C, Goldsmit G, Lemus L, Miura E, Pellicer A, Pérez JM, Rogido M, Zambosco G, van Overmeire B; Primer Grupo de Consenso Clínico SIBEN. [First SIBEN clinical consensus: diagnostic and therapeuti — View Citation

Hernando BG, et al. Atención médica a niños < 30 semanas de gestación con conducto arterioso persistente. Rev Mex Pediatr. 2013; 80 (4): 131-135.

Kim HK, et al. Effect of indomethacin treatment in full-term infants with symptomatic patent ductus arteriosus. Korean J Perinatol 2013; 24 (4): 237-43.

Kwon NH, Lee JH, et al. Risk Factors of Failure of Ibuprofen Treatment in Preterm Infants with HS PDA. Korean J Perinatol 2014; 25 (4): 257-65.

Lam JY, Lopushinsky SR, Ma IW, Dicke F, Brindle ME. Treatment Options for Pediatric Patent Ductus Arteriosus: Systematic Review and Meta-analysis. Chest. 2015 Sep;148(3):784-93. doi: 10.1378/chest.14-2997. Review. — View Citation

Lee JH, Ro SK, Lee HJ, Park HK, Chung WS, Kim YH, Kang JH, Kim H. Surgical Ligation on Significant Patent Ductus Arteriosus in Very Low Birth Weight Infants: Comparison between Early and Late Ligations. Korean J Thorac Cardiovasc Surg. 2014 Oct;47(5):444- — View Citation

López Sousa M, Pérez Feal A, Soto A, Fraga JM, Couce ML. [Left vocal cord paralysis after patent ductus arteriosus surgery]. An Pediatr (Barc). 2015 Jan;82(1):e7-e11. doi: 10.1016/j.anpedi.2014.04.001. Epub 2014 May 10. Spanish. — View Citation

Moore GP, Lawrence SL, Maharajh G, Sumner A, Gaboury I, Barrowman N, Lemyre B. Therapeutic strategies, including a high surgical ligation rate, for patent ductus arteriosus closure in extremely premature infants in a North American centre. Paediatr Child — View Citation

Mosalli R, Alfaleh K. Prophylactic surgical ligation of patent ductus arteriosus for prevention of mortality and morbidity in extremely low birth weight infants. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006181. doi: 10.1002/14651858.CD006181.pub2. Re — View Citation

Sadeck LS, Leone CR, Procianoy RS, Guinsburg R, Marba ST, Martinez FE, Rugolo LM, Moreira ME, Fiori RM, Ferrari LL, Menezes JA, Venzon PS, Abdallah VQ, Duarte JL, Nunes MV, Anchieta LM, Alves Filho N. Effects of therapeutic approach on the neonatal evolut — View Citation

San Luis-Miranda R, Arias-Monroy LG, Peralta-Pedrero ML, Lázaro-Castillo JL, León-Ávila JL, Benítez-Aréchiga ZM, Jáuregui-Ruiz O, Yáñez-Gutiérrez L, Manrique-Valle M. [Clinical guide practice. Patent ductus arteriosus]. Rev Med Inst Mex Seguro Soc. 2012 J — View Citation

Staines OH, Fuentes TMA, Staines AR. Tratamiento quirúrgico del conducto arterioso persistente. Rev Mex Cir Ped 2005; 12: 39-45.

Sung SI, Choi SY, Park JH, Lee MS, Yoo HS, Ahn SY, Chang YS, Park WS. The timing of surgical ligation for patent ductus arteriosus is associated with neonatal morbidity in extremely preterm infants born at 23-25 weeks of gestation. J Korean Med Sci. 2014 — View Citation

Van Overmeire B, Chemtob S. The pharmacologic closure of the patent ductus arteriosus. Semin Fetal Neonatal Med. 2005 Apr;10(2):177-84. Epub 2004 Dec 15. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Time from diagnosis to resolution of patent ductus arteriosus	To compare the time from diagnosis to resolution of patent ductus arteriosus (days)	1 month	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	Death before discharge	To compare related mortality among surgical and pharmacological treatment (%)	1 month	Yes
Secondary	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	Yes
Secondary	Anatomy of the ductus arteriosus persistent	Describe the size of the ductus arteriosus (mm)	1 month	Yes
Secondary	Gestational age at birth	Describe the gestational age of neonates (weeks)	At birth	Yes
Secondary	Apgar	Describe the Apgar score of newborns (3-9)	At birth	Yes
Secondary	Blood flow	Describe the direction of blood flow of the ductus arteriosus (left-right, left-right, two-way)	1 month	Yes
Secondary	Gradient of the ductus arteriosus	Describe the gradient of the ductus arteriosus (mmHg).	1 month	Yes