Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus

May 4, 2012 updated by: Maria Carmen Bravo Laguna, Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

Randomised Controlled Clinical Trial of Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus: a Pilot Study

Patent ductus arteriosus (PDA) is a very common condition in immature newborn babies and it has been associated to morbidity and mortality. Ibuprofen is the drug of choice for PDA treatment according to the last version of the Cochrane review. Nowadays the best dose regimen for ibuprofen remains uncertain. The investigators aim to perform a randomized controlled clinical trial to assess whether echocardiographically guided PDA ibuprofen treatment versus standard treatment could reduce the number of doses of ibuprofen without increasing the reopening rate and reducing the side effects associated to this medication.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Patent ductus arteriosus (PDA) is presented in 55 to 70% of the preterm infants with a gestational age lower than 30 weeks or a birth weight lower than 1000 grams. PDA has being associated to mortality or morbidity such as ischemic or hemorrhagic cerebral events, necrotising enterocolitis, renal disfunction or poor pulmonary outcome; however, it is not clear whether these are a consequence of the PDA presence, the treatment implemented for closing it, or the immaturity of these population. PDA standard treatment (ST) consists on three doses of indomethacin or ibuprofen (10-5-5mg/kg) given 24 hours apart, being the surgical closure a second line therapeutic option. In spite of ibuprofen has been pointed as the drug of choice for PDA treatment by the last version of the Cochrane review, side effects have been associated to both medication. Standard ibuprofen treatment is based on a clinical trial where the three-dose protocol seemed to be more effective than one-dose scheme for PDA closure; however, the sample size was not powered to find differences statistically significant, so nowadays the best dose regimen for ibuprofen remains uncertain. Functional echocardiographic assessment is spreading to all over the world. In this scenario, it has been proposed its implementation to guide PDA treatment in order to individualize the number of doses of indomethacin administered as a function of patient's response, limiting the doses and side effects in those where PDA presented an early constriction. The investigators hypothesized whether echocardiographically guided PDA ibuprofen treatment could reduce the number of doses of ibuprofen without increasing the reopening rate and reducing the side effects associated to this medication.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28046
        • Department of Neonatology, La Paz University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 1 month (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Preterm infants with a gestational age lower than 37 weeks of gestational age
  • PDA ≥ 1.5 mm
  • No contraindication to receive ibuprofen
  • Informed consent signed.

Exclusion Criteria:

  • Life-threatening congenital defects
  • Congenital heart disease
  • Contraindication for ibuprofen administration such as oligoanuria < 1cc/kg/h or recent severe intraventricular bleeding (IVH grade III) or creatinine serum level > 1.5 mg/dl or potential intestinal ischemia.
  • Informed consent refused

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: EchoG
Infants in the experimental group (echoG treatment) received additional doses of ibuprofen only if PDA was still ≥ 1.5 mm at the time of the corresponding ibuprofen dose.
Drug: Ibuprofen EchoG
Infants in the experimental group (echoG treatment) received additional doses of ibuprofen only if PDA was still ≥ 1.5 mm at the time of the corresponding ibuprofen dose.
Other Names:
  • Echocardiographically guided ibuprofen treatment
Other: ST (standard treatment)
Infants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated.
Drug: Standard ibuprofen treatment
Infants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
PDA re-opening rate
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
PDA re-opening after echocardiographically documented closure, which the attending physician deemed amenable to additional treatment. Infants with ventilator weaning difficulty, protracted metabolic acidosis or persistent hemodynamic instability were included in this category.
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
treatment failure
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
PDA ≥ 1.5 mm 24 hours after a complete ibuprofen course
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
need for surgical ligation
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
need for surgical ligation
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
need for additional ibuprofen doses
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
need for additional ibuprofen doses after treatment was completed
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
urine output
Time Frame: before the first ibuprofen dose was administered (between 12-72 hours of life) until 24 hours after the last dose of ibuprofen was administered (between 36-168 h of life)
urine output
before the first ibuprofen dose was administered (between 12-72 hours of life) until 24 hours after the last dose of ibuprofen was administered (between 36-168 h of life)
serum creatinine
Time Frame: before the first ibuprofen dose was administered (between 12-72 hours of life) until 24 hours after the last dose of ibuprofen was administered (between 36-168 h of life)
serum creatinine
before the first ibuprofen dose was administered (between 12-72 hours of life) until 24 hours after the last dose of ibuprofen was administered (between 36-168 h of life)
mortality
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
mortality
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
bronchopulmonary dysplasia
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
bronchopulmonary dysplasia (O2 need at 36 postmenstrual weeks)
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
necrotising enterocolitis
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
necrotising enterocolitis
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
intraventricular hemorrhage
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
intraventricular hemorrhage
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
White matter damage
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
White matter damage
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
Laser therapy for retinopathy
Time Frame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
Laser therapy for retinopathy
Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
peak systolic velocity
Time Frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
peak systolic velocity measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
end-diastolic velocity
Time Frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
end-diastolic velocity measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
resistance index
Time Frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
resistance index measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
pulsatility index
Time Frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
pulsatility index measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: María Carmen Bravo, PhD MD, Department of Neonatology, La Paz University Hospital
  • Study Chair: Fernando Cabañas, PhDMD, Department of Neonatology, La Paz University Hospital
  • Study Chair: Joan Riera, Bio-Engineer, Department of Neonatology, La Paz University Hospital
  • Study Chair: Elia Pérez-Fernández, Division of Statistics, La Paz University Hospital. Madrid, Spain.
  • Study Chair: José Quero, PhDMD, Department of Neonatology, La Paz University Hospital. Madrid, Spain.
  • Study Chair: Jesús Pérez-Rodríguez, PhDMD, Department of Neonatology, La Paz University Hospital. Madrid, Spain.
  • Study Director: Adelina Pellicer, PhDMD, Department of Neonatology, La Paz University Hospital. Madrid, Spain.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 3, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 8, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IbuEchoG

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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