Extremely Premature InfantsPhase 1/2NCT01149564
Comparison of Oral and Intravenous Ibuprofen for PDA Treatment in Premature Infants
A Phase 1/2 study testing iv ibuprofen and oral ibuprofen in people with Extremely Premature Infants and PDA, run by China Medical University Hospital at 1 site in Taiwan.
Trial summary
Background: Patent ductus arteriosus (PDA) continues to be one of the most common problems in premature infants. Pharmacological closure of PDA with intravenous (IV) indomethacin was first reported in 1976, however, concern remains regarding the safety of indomethacin, which affects renal, GI and cerebral perfusion… Read more about this study
- Who is it for?
- Ages 3 to 24 hours
- Conditions the study is for
- Extremely Premature Infants, PDA, Oral Ibuprofen
- What is being tested?
- iv ibuprofen and oral ibuprofen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteTaiwan
- Study dates
- Dec 2009to Jun 2012
- Phase
- Phase 1/2
- 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 3 to 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- premature infants gestational age < 28 weeks, respiratory distress syndrome requiring assisted ventilation, a PDA without other cardiac anomalies confirmed by echocardiography within 24 hours after birth,
Who cannot join
- severe congenital anomalies or lethal cardiopulmonary conditions, and informed consent could be obtained from parents
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
China Medical University Hospital
Taichung, 404
Bai-Horng Su, MD, PhD, 886-4-22052121 ext. 2531, bais@ms49.hinet.net
Bai-Horng Su, MD, PhD
About this study
Official title: Comparison of Oral and Intravenous Ibuprofen for Treatment of Patent Ductus Arteriosus in Extremely Premature Infants: A Randomized Controlled Trial
Background:
Patent ductus arteriosus (PDA) continues to be one of the most common problems in premature infants. Pharmacological closure of PDA with intravenous (IV) indomethacin was first reported in 1976, however, concern remains regarding the safety of indomethacin, which affects renal, GI and cerebral perfusion and may lead to complications such as transient or permanent renal dysfunction, NEC, GI hemorrhage, and reduced cerebral oxygenation. Recently, IV ibuprofen has been shown to be effective for the closure of patent ductus arteriosus in premature infants, without reducing mesenteric, renal, or cerebral blood flow. We have developed the echocardiographic PDA flow pattern as a guide for PDA treatment, fewer doses of drugs were needed to achieve acceptable closing rates. We have also reported that IV ibuprofen is as effective as IV indometacin for the PDA treatment in extremely premature infants, without increasing the incidence of complications in a randomised controlled trial. Several studies reported that oral ibuprofen may be effective for PDA treatment. To date there is no firm conclusion as to the efficacy and safety of oral ibuprofen compared with IV ibuprofen for PDA closure in extremely premature infants.
Read more
Objective:
Since the efficacy of pharmacological closure of PDA is related to gestational age, and extremely premature infants carry the highest rate of mortality and morbidity. We intend to conduct a randomized controlled trial to compare oral and intravenous ibuprofen for treatment of PDA in this high-risk population of extremely premature infants.
Methods:
Extremely premature infants (gestational age < 28 weeks) admit to the NICU will be eligible for enrollment. Informed parental consent will be obtained according to the Institutional Review Board's instructions. Extremely premature infants with respiratory distress syndrome (RDS) and PDA confirmed by echocardiography will be randomly assigned to receive either oral or IV ibuprofen. The subsequent doses of ibuprofen are also determined according to our specific echocardiographic PDA flow patterns at intervals of once every 24 hours from the last dose. The dosage of oral or ibuprofen is 10 mg/kg (1 ml) and then 5 mg/kg at 24-hour intervals as indicated by echocardiographic PDA flow pattern.
Sample Size Calculation and Length of the Study Period:
About 50-60 extremely premature infants will be admitted to our NICU each year. To prove with McNemar's Test at a one-sided significance level of 5% and a power of 90% that using oral ibuprofen instead of IV ibuprofen results in comparable PDA closure rates, only 31 extremely premature infants with RDS and PDA have to be enrolled. Allowing for attrition and exclusion from the final study groups, the length of the study period will be safe to set to 2 years.
Expected Results:
We expect to determine whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants and to compare the complications between infants treated with oral ibuprofen and those with IV ibuprofen.
- Conditions
- Extremely Premature Infants, PDA, Oral Ibuprofen, IV Ibuprofen
- Being tested
- iv ibuprofen, oral ibuprofen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iv ibuprofenDrug
oral ibuprofenDrug
| Study group | Role | What they receive |
|---|---|---|
| IV ibuprofen | Placebo comparator | The first dose of either oral or IV ibuprofen will be given at the time the patient is randomized.The subsequent doses of indometacin or ibuprofen are also determined according to the echocardiographic PDA flow patterns at intervals of once every 24 hours from the last dose. The dosage of both oral ibuprofen (Ibuprofen suspension, 20 mg/ml, Yung Shing Co., Taiwan) and IV ibuprofen (PedeaR 20 mg/ml, developed by Orphan Europe and approved by the EMEA) are an initial dose of 10 mg/kg and then 5 mg/kg at 24-hour intervals as indicated by PDA flow pattern. Receives: Drug: iv ibuprofen |
| Oral ibuprofen | Active comparator | Not described Receives: Drug: oral ibuprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is to ascertain whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants.
Number of extremely premature infants with PDA closed or Adverse Events as a Measure of efficiency and safety.
Measured: 1 month
Secondary outcomes (1)
A secondary objective is to compare the complications between infants treated with oral ibuprofen and those treated with IV ibuprofen.
Number of extremely premature infants in each group with PDA closed or Adverse Events as a Measure of efficiency and safety.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2010 (estimated)
- Study startDec 2009
- Primary completionJun 2012 (estimated)
- Study completionJun 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extremely Premature InfantsStudies of the same condition, open and under way.
- More trials run by China Medical University HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Bai-Horng Su, MD, PhD, Study chair, China Medical University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01149564
- Sponsor's protocol ID
- DMR-99
- Other IDs
- DMR-98
- Status last verified
- Jun 2010
- First submitted
- 20 Jun 2010
- Last updated
- 23 Jun 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Oral and Intravenous Ibuprofen for Treatment of Patent Ductus Arteriosus in Extremely Premature Infants: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01149564
- Acronym / sponsor ID
- DMR-99
- Conditions
- Extremely Premature Infants, PDA, Oral Ibuprofen, IV Ibuprofen
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Jun 2012 (estimated)
- Study completion
- Jun 2012 (estimated)
- First posted
- 23 Jun 2010 (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.
Background:
Patent ductus arteriosus (PDA) continues to be one of the most common problems in premature infants. Pharmacological closure of PDA with intravenous (IV) indomethacin was first reported in 1976, however, concern remains regarding the safety of indomethacin, which affects renal, GI and cerebral perfusion and may lead to complications such as transient or permanent renal dysfunction, NEC, GI hemorrhage, and reduced cerebral oxygenation. Recently, IV ibuprofen has been shown to be effective for the closure of patent ductus arteriosus in premature infants, without reducing mesenteric, renal, or cerebral blood flow. We have developed the echocardiographic PDA flow pattern as a guide for PDA treatment, fewer doses of drugs were needed to achieve acceptable closing rates. We have also reported that IV ibuprofen is as effective as IV indometacin for the PDA treatment in extremely premature infants, without increasing the incidence of complications in a randomised controlled trial. Several studies reported that oral ibuprofen may be effective for PDA treatment. To date there is no firm conclusion as to the efficacy and safety of oral ibuprofen compared with IV ibuprofen for PDA closure in extremely premature infants.
Objective:
Since the efficacy of pharmacological closure of PDA is related to gestational age, and extremely premature infants carry the highest rate of mortality and morbidity. We intend to conduct a randomized controlled trial to compare oral and intravenous ibuprofen for treatment of PDA in this high-risk population of extremely premature infants.
Methods:
Extremely premature infants (gestational age < 28 weeks) admit to the NICU will be eligible for enrollment. Informed parental consent will be obtained according to the Institutional Review Board's instructions. Extremely premature infants with respiratory distress syndrome (RDS) and PDA confirmed by echocardiography will be randomly assigned to receive either oral or IV ibuprofen. The subsequent doses of ibuprofen are also determined according to our specific echocardiographic PDA flow patterns at intervals of once every 24 hours from the last dose. The dosage of oral or ibuprofen is 10 mg/kg (1 ml) and then 5 mg/kg at 24-hour intervals as indicated by echocardiographic PDA flow pattern.
Sample Size Calculation and Length of the Study Period:
About 50-60 extremely premature infants will be admitted to our NICU each year. To prove with McNemar's Test at a one-sided significance level of 5% and a power of 90% that using oral ibuprofen instead of IV ibuprofen results in comparable PDA closure rates, only 31 extremely premature infants with RDS and PDA have to be enrolled. Allowing for attrition and exclusion from the final study groups, the length of the study period will be safe to set to 2 years.
Expected Results:
We expect to determine whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants and to compare the complications between infants treated with oral ibuprofen and those with IV ibuprofen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV ibuprofen | Placebo comparator | Drug: iv ibuprofenThe first dose of either oral or IV ibuprofen will be given at the time the patient is randomized.The subsequent doses of indometacin or ibuprofen are also determined according to the echocardiographic PDA flow patterns at intervals of once every 24 hours from the last dose. The dosage of both oral ibuprofen (Ibuprofen suspension, 20 mg/ml, Yung Shing Co., Taiwan) and IV ibuprofen (PedeaR 20 mg/ml, developed by Orphan Europe and approved by the EMEA) are an initial dose of 10 mg/kg and then 5 mg/kg at 24-hour intervals as indicated by PDA flow pattern. |
| Oral ibuprofen | Active comparator | Drug: oral ibuprofen |
Who may qualify
- Ages
- 3 to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- premature infants gestational age < 28 weeks, respiratory distress syndrome requiring assisted ventilation, a PDA without other cardiac anomalies confirmed by echocardiography within 24 hours after birth,
Key exclusion criteria (1 listed)
- severe congenital anomalies or lethal cardiopulmonary conditions, and informed consent could be obtained from parents
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 |
|---|---|---|
| iv ibuprofen | Drug | IV ibuprofen |
| oral ibuprofen | Drug | Oral ibuprofen |
Primary outcome
The primary outcome is to ascertain whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants.
Time frame: 1 month
Number of extremely premature infants with PDA closed or Adverse Events as a Measure of efficiency and safety.
1 secondary outcome
A secondary objective is to compare the complications between infants treated with oral ibuprofen and those treated with IV ibuprofen.
Time frame: 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2010.
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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.
Bai-Horng Su, MD, PhD study chair
China Medical 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 1/2 study testing iv ibuprofen and oral ibuprofen in people with Extremely Premature Infants and PDA, run by China Medical University Hospital at 1 site in Taiwan.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 23 Jun 2010. 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 Taiwan. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bai-Horng Su, MD, PhD (886-4-22052121 ext. 2061, bais@ms49.hinet.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome is to ascertain whether oral ibuprofen is effective and safe in inducing PDA closure in extremely premature infants. (time frame: 1 month). 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 23 Jun 2010.