Patent Ductus Arteriosus After Premature BirthPhase 2NCT05493540
Oral Ibuprofen Versus Placebo in Treatment of Patent Ductus Arteriosus (PDA)in Preterm Infants
A Phase 2 study testing Ibuprofen oral suspension in people with Patent Ductus Arteriosus After Premature Birth and Patent Ductus Arteriosus Conservative Management, run by Nada Youssef at 1 site in Egypt.
Trial summary
The management options of Patent Ductus Arteriosus are still controversial and differ between centers. Recently, conservative management has been gaining interest as the evidence of benefit from medical treatment in terms of mortality and morbidity is lacking. Read more about this study
- Who is it for?
- Ages 1 hour to 7 days
- Conditions the study is for
- Patent Ductus Arteriosus After Premature Birth, Patent Ductus Arteriosus Conservative Management
- What is being tested?
- Ibuprofen oral suspension
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Apr 2021to 1 Sep 2022
- Phase
- Phase 2
- 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 1 hour to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Gestational age ≤ 34 weeks
- PDA Size > 1.5 mm and predominantly left-to-right shunt
- One of the following:
- Signs of Pulmonary overflow: Left atrium/Aortic diameter ratio (LA/Ao), Left Ventricular End Diastolic Diameter (LVEDD).
- Signs of Systemic Hypo perfusion: Absent or Reversed diastolic flow in the aorta, celiac/mesenteric, or Anterior Cerebral Artery (ACA)/ Middle Cerebral Artery (MCA)
Who cannot join
- Chromosomal anomaly
- Congenital heart defect, other than PDA and/or patent foramen ovale
- Congenital or acquired gastrointestinal anomaly
- Previous episodes of Necrotizing enterocolitis (NEC) or intestinal perforation
- Active bleeding, especially intracranial or gastrointestinal hemorrhage
- Contraindications to the use of ibuprofen
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Oral Ibuprofen Versus Placebo in Management of Patent Ductus Arteriosus in Preterm Infants: A Double Blind, Randomized Control Trial
The management options of Patent Ductus Arteriosus are still controversial and differ between centers. Recently, conservative management has been gaining interest as the evidence of benefit from medical treatment in terms of mortality and morbidity is lacking.
This study will compare oral ibuprofen (the standard treatment) with the conservative treatment, in terms of ductal closure and morbidity and mortality at discharge in preterm neonates less than 34 weeks.
Read the detailed description
A double-blinded, randomized, placebo-control non-inferiority trial was conducted in the neonatal intensive care unit (NICU) of Ain Shams University children's hospital, Cairo, Egypt.
Informed consent was taken from the parents or legal guardians before enrolment, after fully explaining to them the nature of the study. The approval of the Research Ethics Committee at Ain Shams University was also obtained.
All preterm neonates less than 34 weeks were assessed in the first 48 hours by clinical and echocardiographic examination by a cardiologist to detect PDA and exclude any congenital heart disease.
All neonates meeting the inclusion criteria will be randomized into one of two groups:
Medical treatment group and Placebo group. Targeted neonatal Echo was repeated after 5 days of the start of medical treatment by a neonatologist or a cardiologist to assess PDA closure.
After 7 days of intervention, open-label is offered to all patients with the option of another course for patients in the medical treatment group and Rescue therapy in the Placebo group.
The short-term morbidity is documented.
Withdrawal and replacement of individual subjects:
- The attending physician can decide to withdraw a subject from the study for urgent medical reasons. If they wish, parents or caregivers can leave the study at any time for any reason.
- Infants who are withdrawn from the study will be managed according to NICU Protocols.
- Conditions
- Patent Ductus Arteriosus After Premature Birth, Patent Ductus Arteriosus Conservative Management
- Being tested
- Ibuprofen oral suspension, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibuprofen oral suspensionDrug
Also called Active treatment
The medical treatment group will receive oral Ibuprofen with conservative therapy in the form of fluid restriction, Positive End Expiratory Pressure (PEEP), and/or diuretics
An additional course of Ibuprofen may be offered if there is:
- Moderate/Severe PDA on Echocardiography
- Prolonged ventilation or Increased ventilatory setting
- Prolonged use of inotropes or vasopressors or escalating dose
- Another form of treatment may be offered if the patient developed side effects from Ibuprofen
PlaceboDrug
Also called Conservative
Placebo Group will receive Oral Placebo and Conservative therapy in the form of fluid restriction, PEEP, and/or diuretics
An Open-label option might be offered if there are concerns by attending physicians over the poor patient condition that might be attributed to persistent PDA:
- Prolonged Ventilation or Escalating Ventilatory Setting
- Prolonged Use Of Inotropes or Vasopressors or escalation of Doses
Rescue therapy in the form of a course of oral ibuprofen may be offered:
- After 5 days of recruitment
- Moderate/Severe PDA on Echocardiography
- Prolonged ventilation or Increased ventilatory setting
- Prolonged use of inotropes or vasopressors or escalating dose - Another form of treatment may be offered if the patient developed side effects from Ibuprofen
| Study group | Role | What they receive |
|---|---|---|
| Medical treatment Group | Active comparator | 40 preterm neonates will receive Ibuprofen oral suspension Receives: Drug: Ibuprofen oral suspension |
| Placebo Group | Placebo comparator | 40 preterm neonates will receive oral placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of PDA Closure by Echocardiography
Compare the incidence of PDA closure assessed by Echocardiography during hospitalization between the two groups
Measured: Hospital discharge (approximately 3 months unless death occurs first)
Secondary outcomes (5)
Incidence of death during hospitalization
Compare the incidence of death during hospitalization between the two groups
Measured: Hospital discharge (approximately 3 months unless death occurs first)
Incidence of Necrotizing Enterocolitis (NEC)
Compare the incidence of NEC during hospitalization between the two groups by Bell's staging
Measured: Hospital discharge (approximately 3 months unless death occurs first)
Incidence of Bronchopulmonary dysplasia (BPD)
Compare the Incidence of BPD (needing supplemental oxygen at 28 days of life) during hospitalization between the two groups
Measured: Hospital discharge (approximately 3 months unless death occurs first)
Incidence of Sepsis
Compare the Incidence of sepsis during hospitalization between the two groups by positive blood culture.
Measured: Hospital discharge (approximately 3 months unless death occurs first)
Incidence of Intraventricular hemorrhage (IVH)
Compare the Incidence of IVH during hospitalization between the two groups by transcranial ultrasound
Measured: Hospital discharge (approximately 3 months unless death occurs first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2022
- Study start15 Apr 2021
- Primary completion15 Aug 2022
- Study completion1 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patent Ductus Arteriosus After Premature BirthStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nada Youssef
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nada Youssef, Ain Shams University
- Investigators
- Nada H Youssef, Principal investigator, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05493540
- Sponsor's protocol ID
- MD 96 2020
- Status last verified
- Feb 2023
- First submitted
- 2 Aug 2022
- Last updated
- 28 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Ibuprofen Versus Placebo in Management of Patent Ductus Arteriosus in Preterm Infants: A Double Blind, Randomized Control Trial
- ClinicalTrials.gov ID
- NCT05493540
- Acronym / sponsor ID
- MD 96 2020
- Conditions
- Patent Ductus Arteriosus After Premature Birth, Patent Ductus Arteriosus Conservative Management
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Nada YoussefUniversity, hospital or other
- Study start
- 15 Apr 2021 (actual)
- Primary completion
- 15 Aug 2022 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 9 Aug 2022 (actual)
- 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.
The management options of Patent Ductus Arteriosus are still controversial and differ between centers. Recently, conservative management has been gaining interest as the evidence of benefit from medical treatment in terms of mortality and morbidity is lacking.
This study will compare oral ibuprofen (the standard treatment) with the conservative treatment, in terms of ductal closure and morbidity and mortality at discharge in preterm neonates less than 34 weeks.
Detailed description
A double-blinded, randomized, placebo-control non-inferiority trial was conducted in the neonatal intensive care unit (NICU) of Ain Shams University children's hospital, Cairo, Egypt.
Informed consent was taken from the parents or legal guardians before enrolment, after fully explaining to them the nature of the study. The approval of the Research Ethics Committee at Ain Shams University was also obtained.
All preterm neonates less than 34 weeks were assessed in the first 48 hours by clinical and echocardiographic examination by a cardiologist to detect PDA and exclude any congenital heart disease.
All neonates meeting the inclusion criteria will be randomized into one of two groups:
Medical treatment group and Placebo group. Targeted neonatal Echo was repeated after 5 days of the start of medical treatment by a neonatologist or a cardiologist to assess PDA closure.
After 7 days of intervention, open-label is offered to all patients with the option of another course for patients in the medical treatment group and Rescue therapy in the Placebo group.
The short-term morbidity is documented.
Withdrawal and replacement of individual subjects:
- The attending physician can decide to withdraw a subject from the study for urgent medical reasons. If they wish, parents or caregivers can leave the study at any time for any reason.
- Infants who are withdrawn from the study will be managed according to NICU Protocols.
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 |
|---|---|---|
| Medical treatment Group | Active comparator | Drug: Ibuprofen oral suspension40 preterm neonates will receive Ibuprofen oral suspension |
| Placebo Group | Placebo comparator | Drug: Placebo40 preterm neonates will receive oral placebo |
Who may qualify
- Ages
- 1 hour to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Gestational age ≤ 34 weeks
- PDA Size > 1.5 mm and predominantly left-to-right shunt
- One of the following:
- Signs of Pulmonary overflow: Left atrium/Aortic diameter ratio (LA/Ao), Left Ventricular End Diastolic Diameter (LVEDD).
- Signs of Systemic Hypo perfusion: Absent or Reversed diastolic flow in the aorta, celiac/mesenteric, or Anterior Cerebral Artery (ACA)/ Middle Cerebral Artery (MCA)
Key exclusion criteria (6 listed)
- Chromosomal anomaly
- Congenital heart defect, other than PDA and/or patent foramen ovale
- Congenital or acquired gastrointestinal anomaly
- Previous episodes of Necrotizing enterocolitis (NEC) or intestinal perforation
- Active bleeding, especially intracranial or gastrointestinal hemorrhage
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 oral suspensionAlso: Active treatmentThe medical treatment group will receive oral Ibuprofen with conservative therapy in the form of fluid restriction, Positive End Expiratory Pressure (PEEP), and/or diuretics An additional course of Ibuprofen may be offered if there is: 1. Moderate/Severe PDA on Echocardiography 2. Prolonged ventilation or Increased ventilatory setting 3. Prolonged use of inotropes or vasopressors or escalating dose * Another form of treatment may be offered if the patient developed side effects from Ibuprofen | Drug | Medical treatment Group |
| PlaceboAlso: ConservativePlacebo Group will receive Oral Placebo and Conservative therapy in the form of fluid restriction, PEEP, and/or diuretics An Open-label option might be offered if there are concerns by attending physicians over the poor patient condition that might be attributed to persistent PDA: 1. Prolonged Ventilation or Escalating Ventilatory Setting 2. Prolonged Use Of Inotropes or Vasopressors or escalation of Doses Rescue therapy in the form of a course of oral ibuprofen may be offered: 1. After 5 days of recruitment 2. Moderate/Severe PDA on Echocardiography 3. Prolonged ventilation or Increased ventilatory setting 4. Prolonged use of inotropes or vasopressors or escalating dose - Another form of treatment may be offered if the patient developed side effects from Ibuprofen | Drug | Placebo Group |
Primary outcome
Incidence of PDA Closure by Echocardiography
Time frame: Hospital discharge (approximately 3 months unless death occurs first)
Compare the incidence of PDA closure assessed by Echocardiography during hospitalization between the two groups
5 secondary outcomes
Incidence of death during hospitalization
Time frame: Hospital discharge (approximately 3 months unless death occurs first)
Incidence of Necrotizing Enterocolitis (NEC)
Time frame: Hospital discharge (approximately 3 months unless death occurs first)
Incidence of Bronchopulmonary dysplasia (BPD)
Time frame: Hospital discharge (approximately 3 months unless death occurs first)
Incidence of Sepsis
Time frame: Hospital discharge (approximately 3 months unless death occurs first)
Incidence of Intraventricular hemorrhage (IVH)
Time frame: Hospital discharge (approximately 3 months unless death occurs first)
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 28 Feb 2023.
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Patent Ductus Arteriosus After Premature Birth
Active, not recruitingPhase 3
Management of the PDA Trial
Infant, Premature, Patent Ductus Arteriosus
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.
Nada H Youssef principal investigator
Ain Shams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibuprofen oral suspension in people with Patent Ductus Arteriosus After Premature Birth and Patent Ductus Arteriosus Conservative Management, run by Nada Youssef at 1 site in Egypt.
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 5 inclusion and 6 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 28 Feb 2023. 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 Egypt. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Incidence of PDA Closure by Echocardiography (time frame: Hospital discharge (approximately 3 months unless death occurs first)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Feb 2023.