Patent Ductus ArteriosusPhase 3NCT01593163
Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus
A Phase 3 study testing Ibuprofen EchoG and Standard ibuprofen treatment in people with Patent Ductus Arteriosus, run by Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz at 1 site in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 1 month
- Conditions the study is for
- Patent Ductus Arteriosus
- What is being tested?
- Ibuprofen EchoG and Standard ibuprofen treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteSpain
- Study dates
- May 2009to Mar 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 1 month
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site
Department of Neonatology, La Paz University Hospital
Madrid, Madrid, 28046
About this study
Official title: 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.
Read the 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.
- Conditions
- Patent Ductus Arteriosus
- Being tested
- Ibuprofen EchoG, Standard ibuprofen treatment
- Keywords
- Functional echocardiography, power Doppler cranial ultrasonography, N-terminal probrain natriuretic peptide, Patent ductus arteriosus
- Medical subject headings
- Ductus Arteriosus, Patent
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibuprofen EchoGDrug
Also called Echocardiographically guided ibuprofen treatment
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.
Standard ibuprofen treatmentDrug
Infants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated.
| Study group | Role | What they receive |
|---|---|---|
| EchoG | Experimental | 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. Receives: Drug: Ibuprofen EchoG |
| ST (standard treatment) | Other | Infants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated. Receives: Drug: Standard ibuprofen treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
PDA re-opening rate
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.
Measured: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
Secondary outcomes (15)
treatment failure
PDA ≥ 1.5 mm 24 hours after a complete ibuprofen course
Measured: 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
need for surgical ligation
Measured: 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
need for additional ibuprofen doses after treatment was completed
Measured: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
urine output
urine output
Measured: 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
serum creatinine
Measured: 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
mortality
Measured: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
bronchopulmonary dysplasia
bronchopulmonary dysplasia (O2 need at 36 postmenstrual weeks)
Measured: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
necrotising enterocolitis
necrotising enterocolitis
Measured: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
intraventricular hemorrhage
intraventricular hemorrhage
Measured: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
White matter damage
White matter damage
Measured: 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
Laser therapy for retinopathy
Measured: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
peak systolic velocity
peak systolic velocity measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
Measured: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
end-diastolic velocity
end-diastolic velocity measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
Measured: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
resistance index
resistance index measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
Measured: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
pulsatility index
pulsatility index measured by means of cerebral Doppler ultrasonography in the anterior and middle cerebral arteries
Measured: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2012 (estimated)
- Study startMay 2009
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Patent Ductus ArteriosusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maria Carmen Bravo Laguna, Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
- Investigators
- María Carmen Bravo, PhD MD, Principal investigator, Department of Neonatology, La Paz University HospitalFernando Cabañas, PhDMD, Study chair, Department of Neonatology, La Paz University HospitalJoan Riera, Bio-Engineer, Study chair, Department of Neonatology, La Paz University HospitalElia Pérez-Fernández, Study chair, Division of Statistics, La Paz University Hospital. Madrid, Spain.José Quero, PhDMD, Study chair, Department of Neonatology, La Paz University Hospital. Madrid, Spain.Jesús Pérez-Rodríguez, PhDMD, Study chair, Department of Neonatology, La Paz University Hospital. Madrid, Spain.Adelina Pellicer, PhDMD, Study director, Department of Neonatology, La Paz University Hospital. Madrid, Spain.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01593163
- Sponsor's protocol ID
- IbuEchoG
- Status last verified
- May 2012
- First submitted
- 3 May 2012
- Last updated
- 8 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Carmo KB, Evans N, Paradisis M. Duration of indomethacin treatment of the preterm patent ductus arteriosus as directed by echocardiography. J Pediatr. 2009 Dec;155(6):819-822.e1. doi: 10.1016/j.jpeds.2009.06.013. Epub 2009 Jul 29.
PubMed 19643435
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Controlled Clinical Trial of Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus: a Pilot Study
- ClinicalTrials.gov ID
- NCT01593163
- Acronym / sponsor ID
- IbuEchoG
- Conditions
- Patent Ductus Arteriosus
- Keywords
- Functional echocardiography, power Doppler cranial ultrasonography, N-terminal probrain natriuretic peptide, Patent ductus arteriosus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario la PazUniversity, hospital or other
- Study start
- May 2009
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 8 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EchoG | Experimental | Drug: Ibuprofen EchoGInfants 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. |
| ST (standard treatment) | Other | Drug: Standard ibuprofen treatmentInfants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated. |
Who may qualify
- Ages
- Up to 1 month
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ibuprofen EchoGAlso: Echocardiographically guided ibuprofen treatmentInfants 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 | EchoG |
| Standard ibuprofen treatmentInfants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated. | Drug | ST (standard treatment) |
Primary outcome
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.
15 secondary outcomes
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
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 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
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)
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)
mortality
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
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
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
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
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
Time frame: 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
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
resistance 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
Time frame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2012.
- Background: PubMed 19643435Carmo KB, Evans N, Paradisis M. Duration of indomethacin treatment of the preterm patent ductus arteriosus as directed by echocardiography. J Pediatr. 2009 Dec;155(6):819-822.e1. doi: 10.1016/j.jpeds.2009.06.013. Epub 2009 Jul 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
María Carmen Bravo, PhD MD principal investigator
Department of Neonatology, La Paz University Hospital
Fernando Cabañas, PhDMD study chair
Department of Neonatology, La Paz University Hospital
Joan Riera, Bio-Engineer study chair
Department of Neonatology, La Paz University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ibuprofen EchoG and Standard ibuprofen treatment in people with Patent Ductus Arteriosus, run by Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01593163, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2012.