Clinical Trial to Evaluate Two Guidelines for the Administration of Ibuprofen in the Treatment of Persistent Ductus Arteriosus Eco-guided: Impact in the Intestinal Prognosis

NCT04282941 | Unknown Phase 3

• 1 other identifier: 2016-002974-11
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 3

Brief Summary

Persistent ductus arteriosus (DA) is a common entity in the premature newborn and is associated with high morbidity and mortality. There is still controversy about which is the best treatment for its closure. Children with AD who receive pharmacological treatment present more frequently than other premature children, necrotizing enterocolitis or isolated intestinal perforation. At the present time, the conventional treatment of DA consists in the administration of intravenous ibuprofen, slow bolus in 3 daily doses 10-5-5 mg / kg / day. Recently, it has been observed that treatment with ibuprofen in continuous iv infusion for 3 days seems to be more effective in closing DA than conventional treatment for 3 days with the same dose but in slow iv bolus. This experimental treatment reduced the incidence of associated necrotizing enterocolitis. Our group demonstrated in a previous pilot trial that the guided treatment with echocardiography (EchoG) of DA with ibuprofen compared with conventional treatment, allows to reduce the number of doses to the patient. The EchoG treatment thus presents a potential reduction of side effects associated with medication, this resulted in a tendency to have a lower incidence of necrotising enterocolitis in the experimental group. This multicenter clinical trial aims to test the hypothesis that the combination of 2 experimental treatments, the use of ibuprofen in continuous perfusion and EchoG, reduces the incidence of digestive side effects (necrotising enterocolitis or isolated intestinal perforation) compared to the treatment also guided by echocardiography but slow bolus iv.

Conditions

Persistent Ductus Arteriosus

Outcome Measures

Primary Outcomes (1)

• Change the incidence of necrotizing enterocolitis or isolated intestinal perforation in preterm infants receiving treatment for closure of AD with ibuprofen in continuous IV perfusion and EchoG vs iv and EchoG boluses

  Change the incidence of necrotizing enterocolitis or isolated intestinal perforation in preterm infants receiving treatment for closure of AD with ibuprofen in continuous IV perfusion and EchoG vs iv and EchoG boluses

  40 weeks

Secondary Outcomes (1)

• To Identify genetic polymorphisms asociated to refractory medical treatment of AD and in those most vulnerable to presenting necrotizing enterocolitis or isolated intestinal perforation.

  Day 0(Visit 1)

Other Outcomes (2)

• To Assess the incidence of neonatal morbidity associated with each of the forms of treatment

  up to 40 Weeks Postmenstrual age

• To Assess the neonatal mortality associated with each of the forms of treatment

  up to 40 Weeks Postmenstrual age

Study Arms (2)

Ibuprofen in continuous (24 hours) iv infusion and EchoG

EXPERIMENTAL

The first dose of ibuprofen will be 10 mg / kg to be administered as a continuous infusion for 24 hours. An echocardiogram will be performed before each of the following 2 doses of 5 mg / Kg and will only be administered if it meets echocardiographic criteria that indicate open DA (observation of ductus permeability with color Doppler regardless of its size). Each dose will be administered as a 24-hour continuous infusion.

Drug: Ibuprofen in continuous (24 hours) iv infusion and EchoG

IV bolus Ibuprofen slow (15 minutes) and EchoG

EXPERIMENTAL

The first dose of ibuprofen of 10 mg / Kg to be administered in slow iv bolus (15 minutes). Before each of the following 2 doses of 5 mg / Kg, echocardiography will be performed and will only be administered if it meets the echocardiographic criteria indicated by open DA (observation of ductus permeability in color Doppler regardless of its size). Each dose will be administered in iv boluses in 15 minutes

Drug: IV bolus Ibuprofen slow (15 minutes) and EchoG

Interventions

Ibuprofen in continuous (24 hours) iv infusion and EchoG DRUG

The first dose of ibuprofen will be 10 mg / kg to be administered as a continuous infusion for 24 hours. An echocardiogram will be performed before each of the following 2 doses of 5 mg / Kg and will only be administered if it meets echocardiographic criteria that indicate open DA (observation of ductus permeability with color Doppler regardless of its size). Each dose will be administered as a 24-hour continuous infusion.

Ibuprofen in continuous (24 hours) iv infusion and EchoG

IV bolus Ibuprofen slow (15 minutes) and EchoG DRUG

The first dose of ibuprofen of 10 mg / Kg to be administered in slow iv bolus (15 minutes). Before each of the following 2 doses of 5 mg / Kg, echocardiography will be performed and will only be administered if it meets the echocardiographic criteria indicated by open DA (observation of ductus permeability in color Doppler regardless of its size). Each dose will be administered in iv boluses in 15 minutes

IV bolus Ibuprofen slow (15 minutes) and EchoG

Eligibility Criteria

• Age: 0 Minutes - 33 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infants with less 33 weeks of gestational age
• DA ≥ 1.5 mm with decision to start pharmacological treatment
• Informed consent signed by the legal representative

You may not qualify if:

• Consent denied
• Presence of serious congenital alterations
• Congenital heart disease
• Contraindication for the administration of IB: oligoanuria (diuresis \<1cc / kg / h), bleeding severe recent intraventricular (HIV grade III or extensive periventricular hemorrhagic infarction), serum creatinine\> 1.5 mg / dl or clinical suspicion of intestinal ischemia.

Sponsors & Collaborators

• Instituto de Investigación Hospital Universitario La Paz: lead

Study Sites (3)

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital 12 de Octubre

Madrid, Spain

RECRUITING

Hospital Quirón Salud Madrid

Madrid, Spain

RECRUITING

MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

Ibuprofen; Infusions, Intravenous

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: A randomized system with closed envelopes will be designed in which patients will be assigned to one of the 2 treatment groups, stratified by gestational age (\<28 weeks and ≥28 weeks) and by hospital center. In each center and each stratum, they will be randomly assigned in a 1: 1 ratio to each group of study. The assignment will be sequential. The doctors responsible for the patient will be blind to the intervention but will be responsible for the sealed envelopes, and at the time of patient randomization, will deliver the sealed envelope corresponding to the nurses responsible for the preparation of the medication.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Administration schedule A: Ibuprofen in continuous iv infusion and EchoG. Each cycle will be 3 doses. Administration schedule B: slow iv bolus Ibuprofen and EchoG. Each cycle will be 3 doses.

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 25, 2020
• Study Start: February 20, 2017
• Primary Completion: January 30, 2020
• Study Completion: November 30, 2020
• Last Updated: October 29, 2020

Record last verified: 2020-07

Locations

ES (3)