Patent Ductus ArteriosusNCT00802685
Timing of PDA Closure and Respiratory Outcome in Premature Infants
A study testing Early ibuprofen in people with Patent Ductus Arteriosus, run by University of Miami at 1 site in United States.
Trial summary
The investigators propose the present study with the following aims: to determine whether early patent ductus arteriosus (PDA) treatment with ibuprofen treatment at the onset of clinical symptoms is superior to late ibuprofen treatment only when symptoms of a hemodynamically significant PDA are present in the… Read more about this study
- Who is it for?
- Ages 1 day to 14 days
- Conditions the study is for
- Patent Ductus Arteriosus
- What is being tested?
- Early ibuprofen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Feb 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 day to 14 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Inborn patients at JHS hospitals (admitted to the NICU at JMH within the first 72 hrs of age
- BW 500-1250 grams
- 23-32 wks gestational age
- > 1d but < 14d of age.
Who cannot join
- Major congenital malformations
- Proven sepsis (positive blood culture)
- Contraindications to the use of Ibuprofen or Indomethacin
- Terminal condition, not expected to survive beyond 48 h
- Infants born excessively SGA(3 S.D. below the mean for GA)
- Infants with initial PDA presentation that is hemodynamically significant
Trial locations and contacts
1 site in 1 country.
United States1 site
Jackson Memorial Hospital/Holtz Children's Center
Miami, Florida, 33136
About this study
The investigators propose the present study with the following aims:
- to determine whether early patent ductus arteriosus (PDA) treatment with ibuprofen treatment at the onset of clinical symptoms is superior to late ibuprofen treatment only when symptoms of a hemodynamically significant PDA are present in the evolution of bronchopulmonary dysplasia (BPD) defined as duration of supplemental oxygen exposure during the first 28 days
- to determine whether early PDA treatment with ibuprofen will be superior to late treatment with ibuprofen in efficacy of PDA closure, need for rescue therapy, need for PDA ligation and incidence of major complications of prematurity.
Read more
Hypothesis: Early pharmacologic closure of PDA with ibuprofen will improve respiratory course and reduce BPD as reflected by a reduction in duration of supplemental oxygen during the first 28 days of age vs. late pharmacologic treatment with ibuprofen.
Outcome variables: The primary outcome of this study is the number of days spent on supplemental oxygen by each infant during the first 28 days.
Other outcomes to be determined between groups include:
- Mortality
- Other respiratory variables: total days on supplemental oxygen, days on mechanical ventilation, oxygen dependence at 36 weeks post menstrual age, age at final extubation.
- Other respiratory complications: pneumothorax, pulmonary interstitial emphysema, need for high frequency ventilation, pulmonary hypertension
- Efficacy of PDA closure: number of courses of medication required, need for ligation
- Other neonatal complications: intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intestinal perforation, sepsis, renal dysfunction (oliguria, elevated creatinine)
- Time to achieving full enteral feedings, time to regain birth weight, weight at discharge.
- Length of hospital stay
Read the detailed description
Study terminated when intravenous (IV) ibuprofen withdrawn for both clinical and research use.
- Conditions
- Patent Ductus Arteriosus
- Being tested
- Early ibuprofen, Late ibuprofen expectant group (placebo)
- Keywords
- Patent ductus arteriosus, Respiratory outcome
- 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.
Early ibuprofenDrug
IBUPROFEN SCHEDULE: initial dose 10 mg/kg, then 2 doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Initial therapy is blinded. At PDA diagnosis, infants randomized to "early treatment" receive blinded ibuprofen. Infants randomized to "late treatment" receive blinded placebo. Hemodynamically significant PDA criteria: SIGNS OF PDA + pulmonary hemorrhage OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due to PDA) defined as at least two of the following: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. Once hemodynamically significant PDA criteria met, if echo is positive, infants from both groups can receive open label ibuprofen.
Late ibuprofen expectant group (placebo)Other
Drug: Late ibuprofen expectant group (placebo): DOSING SCHEDULE: At PDA diagnosis infants randomized to "late ibuprofen expectant group" will receive blinded placebo. If hemodynamically significant PDA develops, infants now receive open label ibuprofen at an initial dose of 10 mg/kg, then two doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Signs of a hemodynamically significant PDA include: SIGNS OF PDA + pulmonary hemorrhage ALONE OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due PDA) defined as at least 2 of the following settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV.
| Study group | Role | What they receive |
|---|---|---|
| early ibuprofen | Experimental | Drug: Early ibuprofen
IBUPROFEN DOSING SCHEDULE: At the diagnosis of PDA, infants randomized to "early treatment" will receive blinded ibuprofen initial dose 10 mg/kg, then two doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Initial therapy will be blinded. This group will then be eligible to receive unblinded, open label ibuprofen for a hemodynamically significant PDA include: SIGNS OF PDA + Presence of significant pulmonary hemorrhage ALONE OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (not due to something other than PDA) defined as at least two of the following respirator settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. Receives: Drug: Early ibuprofen |
| Late Ibuprofen expectant group (placebo) | Other | Late ibuprofen expectant group (placebo): Ibuprofen schedule: At PDA diagnosis, infants randomized to "late expectant group" will receive blinded placebo. If hemo-dynamically significant PDA develops, infants now receive open label ibuprofen, initial dose of 10 mg/kg, then 2 doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Signs of a hemodynamically significant PDA: Signs of PDA + pulmonary hemorrhage alone or Signs of PDA + Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due to PDA) defined as at least two of the following respirator settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. Infants who had received placebo will ibuprofen for the first time (thus, "late" ibuprofen or expectant). Receives: Other: Late ibuprofen expectant group (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days Spent on Supplemental Oxygen During the First 28 Days.
Measured: 28 days of life
Secondary outcomes (1)
Number of Participants on Oxygen at 36 Weeks Postmenstrual Age
Measured: at 36 weeks postmenstrual age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2008 (estimated)
- Study startNov 2007
- Primary completionAug 2010
- Study completionFeb 2011
Why it stopped: Lack of availability of IV ibuprofen as of 8/10 due to a manufacturer's recall
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Patent Ductus ArteriosusStudies of the same condition, open and under way.
- More trials run by University of MiamiThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- H. Lundbeck A/S
- Responsible party
- Principal investigator, Ilene R.S. Sosenko, M.D., University of Miami
- Investigators
- Ilene RS Sosenko, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00802685
- Sponsor's protocol ID
- 20070871
- Status last verified
- Dec 2013
- First submitted
- 4 Dec 2008
- Last updated
- 5 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sosenko IR, Fajardo MF, Claure N, Bancalari E. Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: a double-blind randomized controlled trial. J Pediatr. 2012 Jun;160(6):929-35.e1. doi: 10.1016/j.jpeds.2011.12.031. Epub 2012 Jan 28.
PubMed 22284563
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Timing of PDA Closure and Respiratory Outcome in Premature Infants
- ClinicalTrials.gov ID
- NCT00802685
- Acronym / sponsor ID
- 20070871
- Conditions
- Patent Ductus Arteriosus
- Keywords
- Patent ductus arteriosus, Respiratory outcome
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of availability of IV ibuprofen as of 8/10 due to a manufacturer's recall
- Enrolment
- 105 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- H. Lundbeck A/S
- Study start
- Nov 2007
- Primary completion
- Aug 2010 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 5 Dec 2008 (estimated)
- Results
- Posted 28 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose the present study with the following aims:
- to determine whether early patent ductus arteriosus (PDA) treatment with ibuprofen treatment at the onset of clinical symptoms is superior to late ibuprofen treatment only when symptoms of a hemodynamically significant PDA are present in the evolution of bronchopulmonary dysplasia (BPD) defined as duration of supplemental oxygen exposure during the first 28 days
- to determine whether early PDA treatment with ibuprofen will be superior to late treatment with ibuprofen in efficacy of PDA closure, need for rescue therapy, need for PDA ligation and incidence of major complications of prematurity.
Hypothesis: Early pharmacologic closure of PDA with ibuprofen will improve respiratory course and reduce BPD as reflected by a reduction in duration of supplemental oxygen during the first 28 days of age vs. late pharmacologic treatment with ibuprofen.
Outcome variables: The primary outcome of this study is the number of days spent on supplemental oxygen by each infant during the first 28 days.
Other outcomes to be determined between groups include:
- Mortality
- Other respiratory variables: total days on supplemental oxygen, days on mechanical ventilation, oxygen dependence at 36 weeks post menstrual age, age at final extubation.
- Other respiratory complications: pneumothorax, pulmonary interstitial emphysema, need for high frequency ventilation, pulmonary hypertension
- Efficacy of PDA closure: number of courses of medication required, need for ligation
- Other neonatal complications: intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intestinal perforation, sepsis, renal dysfunction (oliguria, elevated creatinine)
- Time to achieving full enteral feedings, time to regain birth weight, weight at discharge.
- Length of hospital stay
Detailed description
Study terminated when intravenous (IV) ibuprofen withdrawn for both clinical and research use.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| early ibuprofen | Experimental | Drug: Early ibuprofenDrug: Early ibuprofen IBUPROFEN DOSING SCHEDULE: At the diagnosis of PDA, infants randomized to "early treatment" will receive blinded ibuprofen initial dose 10 mg/kg, then two doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Initial therapy will be blinded. This group will then be eligible to receive unblinded, open label ibuprofen for a hemodynamically significant PDA include: SIGNS OF PDA + Presence of significant pulmonary hemorrhage ALONE OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (not due to something other than PDA) defined as at least two of the following respirator settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. |
| Late Ibuprofen expectant group (placebo) | Other | Other: Late ibuprofen expectant group (placebo)Late ibuprofen expectant group (placebo): Ibuprofen schedule: At PDA diagnosis, infants randomized to "late expectant group" will receive blinded placebo. If hemo-dynamically significant PDA develops, infants now receive open label ibuprofen, initial dose of 10 mg/kg, then 2 doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Signs of a hemodynamically significant PDA: Signs of PDA + pulmonary hemorrhage alone or Signs of PDA + Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due to PDA) defined as at least two of the following respirator settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. Infants who had received placebo will ibuprofen for the first time (thus, "late" ibuprofen or expectant). |
Who may qualify
- Ages
- 1 day to 14 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Inborn patients at JHS hospitals (admitted to the NICU at JMH within the first 72 hrs of age
- BW 500-1250 grams
- 23-32 wks gestational age
- > 1d but < 14d of age.
Key exclusion criteria (6 listed)
- Major congenital malformations
- Proven sepsis (positive blood culture)
- Contraindications to the use of Ibuprofen or Indomethacin
- Terminal condition, not expected to survive beyond 48 h
- Infants born excessively SGA(3 S.D. below the mean for GA)
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 |
|---|---|---|
| Early ibuprofenIBUPROFEN SCHEDULE: initial dose 10 mg/kg, then 2 doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Initial therapy is blinded. At PDA diagnosis, infants randomized to "early treatment" receive blinded ibuprofen. Infants randomized to "late treatment" receive blinded placebo. Hemodynamically significant PDA criteria: SIGNS OF PDA + pulmonary hemorrhage OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due to PDA) defined as at least two of the following: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. Once hemodynamically significant PDA criteria met, if echo is positive, infants from both groups can receive open label ibuprofen. | Drug | early ibuprofen |
| Late ibuprofen expectant group (placebo)Drug: Late ibuprofen expectant group (placebo): DOSING SCHEDULE: At PDA diagnosis infants randomized to "late ibuprofen expectant group" will receive blinded placebo. If hemodynamically significant PDA develops, infants now receive open label ibuprofen at an initial dose of 10 mg/kg, then two doses 5 mg/kg each, after 24 and 48 h, slow IV infusion. Signs of a hemodynamically significant PDA include: SIGNS OF PDA + pulmonary hemorrhage ALONE OR SIGNS OF PDA +: Pulmonary edema, plus a large heart on CXR + one of the following: Hypotension, Respiratory failure (due PDA) defined as at least 2 of the following settings: Need for supplemental O2 > 50%; need IMV >40; need for PIP > 20; or need for HFOV. | Other | Late Ibuprofen expectant group (placebo) |
Primary outcome
Days Spent on Supplemental Oxygen During the First 28 Days.
Time frame: 28 days of life
1 secondary outcome
Number of Participants on Oxygen at 36 Weeks Postmenstrual Age
Time frame: at 36 weeks postmenstrual age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22284563Sosenko IR, Fajardo MF, Claure N, Bancalari E. Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: a double-blind randomized controlled trial. J Pediatr. 2012 Jun;160(6):929-35.e1. doi: 10.1016/j.jpeds.2011.12.031. Epub 2012 Jan 28.
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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.
Ilene RS Sosenko, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Early ibuprofen in people with Patent Ductus Arteriosus, run by University of Miami at 1 site in United States.
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 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: stopped early, as of the sponsor's last update on 5 Feb 2014. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Days Spent on Supplemental Oxygen During the First 28 Days. (time frame: 28 days of life). 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 NCT00802685, 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 5 Feb 2014.