Patent Ductus ArteriosusPhase 2NCT03701074
Randomized Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus
A Phase 2 study testing Ibuprofen and acetaminophen in people with Patent Ductus Arteriosus and Preterm Infant, run by University of South Alabama at 1 site in United States.
Trial summary
The purpose of the present study is to determine whether treatment of hemodynamically significant patent ductus arteriosus with a combined therapy of intravenous Ibuprofen and oral acetaminophen has higher success rate in closing the ductus arteriosus than a standard treatment strategy of using intravenous ibuprofen… Read more about this study
- Who is it for?
- Ages 5 to 21 days
- Conditions the study is for
- Patent Ductus Arteriosus, Preterm Infant, Bronchopulmonary Dysplasia
- What is being tested?
- Ibuprofen and acetaminophen
- 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
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2018to 2 Dec 2020
- Phase
- Phase 2
- 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 5 to 21 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm infant ≤27 6/7
- Written parental consent is obtained
- Infant requires respiratory support
- diagnosis of a persistent patent ductus arteriosus after 5 days of age, (defined as at least two of the following:
- Ductus size ≥ 1.5 mm
- Maximum flow velocity through the ductus ≤ 2 m/s
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- Left atrium to aorta ratio ≥ 1.4
- Wide pulse pressure
- B-type natriuretic peptide (BNP)
- Attending neonatologist made decision to treat patent ductus arteriosus
Who cannot join
- No parental consent
- Infants > 21days of postnatal age
- Congenital anomalies such as cardiac or multiple anomalies
- Infection (e.g., septicemia, pneumonia)
- Bleeding disorder or platelet count< 50,000/ml
- Acute kidney injury (AKI)defined as oliguria (urine output< 0.5 ml/kg/hr for 16hrs) and/or serum creatinine > 1.5 mg/dl
Show all 10Show fewer
- Elevated liver enzymes (>2 fold from upper normal limits)
- Pulmonary hypertension or right to left shunt through the ductus arteriosus
- Diagnosis of necrotizing enterocolitis
- Unable to tolerate oral medications at the time of enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single Center, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus
The purpose of the present study is to determine whether treatment of hemodynamically significant patent ductus arteriosus with a combined therapy of intravenous Ibuprofen and oral acetaminophen has higher success rate in closing the ductus arteriosus than a standard treatment strategy of using intravenous ibuprofen alone among preterm infants.
Read the detailed description
The primary objectives of the study are to confirm the safety of oral acetaminophen in extremely low birth infants, given concomitantly with intravenous ibuprofen and also to determine its efficacy in significantly increasing the rates of ductal closure when compared to only intravenous ibuprofen therapy. Hence primary outcome variable include patent ductus arteriosus closure success rate, based on the 2-D transthoracic echocardiographic evidence.
This study is a single center, randomized, double blinded, placebo controlled trial. Preterm infants with gestational age of with a gestational age ≤27 6/7 weeks by the best obstetric estimate are eligible for enrollment.
For randomization, the study population will be stratified to two subgroups based on gestational age (GA ≤24 weeks and > 25 weeks). Randomization will occur by using computer generated random sequence, using a 4-block design, with 1:1 parallel allocation. Allocations include treatment and control arm. Treatment arm will receive combination of intravenous ibuprofen and oral acetaminophen, while control arm will receive intravenous Ibuprofen and oral placebo.
- Being tested
- Ibuprofen and acetaminophen, Ibuprofen and placebo
- Keywords
- patent ductus arteriosus, acetaminophen, ibuprofen, bronchopulmonary dysplasia, mechanical ventilation
- Medical subject headings
- Ductus Arteriosus, Patent, Premature Birth, Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibuprofen and acetaminophenDrug
Intravenous ibuprofen given concomitantly with oral acetaminophen
Ibuprofen and placeboDrug
Intravenous ibuprofen given concomitantly with oral placebo
| Study group | Role | What they receive |
|---|---|---|
| ibuprofen and acetaminophen arm (intervention arm) | Experimental | ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants > 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). Receives: Drug: Ibuprofen and acetaminophen |
| ibuprofen and placebo arm (control arm) | Active comparator | ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants > 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. Receives: Drug: Ibuprofen and placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants With Ductus Arteriosus Closure/Constriction
Ductal closure/constriction rate as defined based on the echocardiographic findings. Ductal closure/constriction will be defined as the complete closure of ductus or ductal diameter <1 mm
Measured: 24-48 hours after the completion of study intervention
Secondary outcomes (22)
Echocardiographic Patent Ductus Arteriosus Parameters Before and After the Study Intervention
Echocardiographic parameters including ductal size (PDA size in mm), Left atrium to aortic root ratio, ductal velocity, descending aortic diastolic flow, before and after the intervention. Between the group and within the group comparison
Measured: 24-48 hours after the completion of study intervention
Ventilatory Settings Before and After the Study Intervention
Ventilator parameters including Fio2, Mean airway pressure, Peak Inspiratory pressure, PEEP, and ventilatory rate oxygenation indices including Oxygenation index and Respiratory Severity score before and after intervention
Measured: 24-48 hours after the completion of study intervention
Proportion of Participants With Liver Injury
liver enzymes compared before and after the study intervention; if any significant elevation of liver enzymes from baseline, the participant classified as having liver injury
Measured: 24-48 hours after the completion of study intervention
Proportion of Participants With Renal Injury
Blood urea nitrogen (BUN) and serum creatinine before and after the study intervention are compared. Participants exhibiting significant elevation BUN and S creatine, are classified as having renal injury
Measured: 24-48 hours after the completion of study intervention
Proportion of Participants With Hematological Adverse Events
Hematocrit and platelet counts compared before and after the study intervention; if any significant alteration from baseline, the participant classified as having hematological adverse event,
Measured: 24-48 hours after the completion of study intervention
Total Number of Days of Mechanical Ventilation
The total number of days on mechanical ventilation are counted as total duration of conventional mechanical ventilation plus high frequency ventilatory days
Measured: from randomization until discharge/40 weeks post menstrual age
Total Number of Days of Need for Supplemental Oxygen
Cumulative days on any supplemental O2 (including Mechanical ventilation., noninvasive ventilation, nasal cannula support) calculated from randomization until 4 weeks of postmenstrual age
Measured: from randomization until discharge/40 weeks post menstrual age
Duration of Noninvasive Ventilation
Total cumulative days on noninvasive ventilation, including NIPPV and nasal CPAP,
Measured: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants With Persistence of Ductus-needing Pharmacological Treatment
Proportion of participants in each group requiring open label treatment with pharmacological agents for ductal closure, e.g. IV Ibuprofen or IV Acetaminophen or IV indomethacin therapies, as decided by the treating physician
Measured: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Requiring Surgical Ligation of PDA
Proportion of participants in each group requiring surgical ligation of persistent PDA for definitive surgical closure
Measured: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Developing Bronchopulmonary Dysplasia
Proportion of participants diagnosed to have BPD based supplemental O2 requirement at 36 weeks' postmenstrual age
Measured: at 36 weeks post menstrual age
Percentage of Infants Requiring Home Oxygen Therapy
Proportion of participants in each group requiring home-based supplemental O2 therapy following the initial discharge from hospital.
Measured: at discharge/40 weeks post menstrual age
Proportion of Participants Developing Death Before Discharge
Proportion of participants in each group developing in-hospital death prior to 40 weeks of postmenstrual age.
Measured: until discharge/40 weeks post menstrual age
Time to Achieve Full Enteral Feeding
Duration days during the postnatal period required to achieve an enteral feeding volume of 120 ml/kg/day.
Measured: from birth until discharge/40 weeks post menstrual age
Total Days on Total Parenteral Nutrition
Cumulative days of receiving total parental nutrition from birth until the participant is discharged or reached postmenstrual age of 40 weeks
Measured: from birth until discharge/40 weeks post menstrual age
Proportion of Participants With Retinopathy of Prematurity
Proportion of participants in each group diagnosed to have retinopathy of prematurity
Measured: from birth until discharge/40 weeks post menstrual age
Proportion of Participants Developing Spontaneous Intestinal Perforation
Proportion of participants developing or having the diagnosis of spontaneous intestinal perforation from randomization until discharge or 40 weeks' Postmenstrual age
Measured: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Developing Necrotizing Enterocolitis
Proportion of participants in each group with the diagnosis of medical or surgical Necrotizing Enterocolitis
Measured: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Developing Gastrointestinal Hemorrhage
Proportion of participants in each group developing gastrointestinal hemorrhage following randomization until discharge or postmenstrual age of 40 weeks
Measured: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Developing Late Onset Sepsis
Proportion of participants diagnosed to have either probable sepsis with minimum of 7 days of antibiotic therapy or culture proven sepsis
Measured: from randomization until discharge/40 weeks post menstrual age
Length of Hospital Stay
Total duration (in days ) of hospital stay
Measured: from birth until discharge/40 weeks post menstrual age
Proportion of Participants With Periventricular Leukomalacia
Proportion of participants in each group with the evidence of periventricular leukomalacia on neurosonography
Measured: from randomization until discharge/40 weeks post menstrual age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2018
- Study start15 Dec 2018
- Primary completion30 Oct 2020
- Study completion2 Dec 2020
Why it stopped: very slow enrollment. Only one patient enrolled. Termination by PI
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of South Alabama
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ramachandra Bhat, University of South Alabama
- Investigators
- Fabien Eyal, MD, Study director, University of South Alabama
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03701074
- Sponsor's protocol ID
- 15-081/730216-8
- Status last verified
- Apr 2026
- First submitted
- 22 Aug 2018
- Last updated
- 30 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Center, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus
- ClinicalTrials.gov ID
- NCT03701074
- Acronym / sponsor ID
- 15-081/730216-8
- Keywords
- patent ductus arteriosus, acetaminophen, ibuprofen, bronchopulmonary dysplasia, mechanical ventilation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: very slow enrollment. Only one patient enrolled. Termination by PI
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of South AlabamaUniversity, hospital or other
- Study start
- 15 Dec 2018 (actual)
- Primary completion
- 30 Oct 2020 (actual)
- Study completion
- 2 Dec 2020 (actual)
- First posted
- 9 Oct 2018 (actual)
- Results
- Posted 11 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the present study is to determine whether treatment of hemodynamically significant patent ductus arteriosus with a combined therapy of intravenous Ibuprofen and oral acetaminophen has higher success rate in closing the ductus arteriosus than a standard treatment strategy of using intravenous ibuprofen alone among preterm infants.
Detailed description
The primary objectives of the study are to confirm the safety of oral acetaminophen in extremely low birth infants, given concomitantly with intravenous ibuprofen and also to determine its efficacy in significantly increasing the rates of ductal closure when compared to only intravenous ibuprofen therapy. Hence primary outcome variable include patent ductus arteriosus closure success rate, based on the 2-D transthoracic echocardiographic evidence.
This study is a single center, randomized, double blinded, placebo controlled trial. Preterm infants with gestational age of with a gestational age ≤27 6/7 weeks by the best obstetric estimate are eligible for enrollment.
For randomization, the study population will be stratified to two subgroups based on gestational age (GA ≤24 weeks and > 25 weeks). Randomization will occur by using computer generated random sequence, using a 4-block design, with 1:1 parallel allocation. Allocations include treatment and control arm. Treatment arm will receive combination of intravenous ibuprofen and oral acetaminophen, while control arm will receive intravenous Ibuprofen and oral placebo.
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 |
|---|---|---|
| ibuprofen and acetaminophen arm (intervention arm) | Experimental | Drug: Ibuprofen and acetaminophenibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants > 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses). |
| ibuprofen and placebo arm (control arm) | Active comparator | Drug: Ibuprofen and placeboibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants > 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals. |
Who may qualify
- Ages
- 5 to 21 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Preterm infant ≤27 6/7
- Written parental consent is obtained
- Infant requires respiratory support
- diagnosis of a persistent patent ductus arteriosus after 5 days of age, (defined as at least two of the following:
- Attending neonatologist made decision to treat patent ductus arteriosus
Key exclusion criteria (10 listed)
- No parental consent
- Infants > 21days of postnatal age
- Congenital anomalies such as cardiac or multiple anomalies
- Infection (e.g., septicemia, pneumonia)
- Bleeding disorder or platelet count< 50,000/ml
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 and acetaminophenIntravenous ibuprofen given concomitantly with oral acetaminophen | Drug | ibuprofen and acetaminophen arm (intervention arm) |
| Ibuprofen and placeboIntravenous ibuprofen given concomitantly with oral placebo | Drug | ibuprofen and placebo arm (control arm) |
Primary outcome
Proportion of Participants With Ductus Arteriosus Closure/Constriction
Time frame: 24-48 hours after the completion of study intervention
Ductal closure/constriction rate as defined based on the echocardiographic findings. Ductal closure/constriction will be defined as the complete closure of ductus or ductal diameter <1 mm
22 secondary outcomes
Echocardiographic Patent Ductus Arteriosus Parameters Before and After the Study Intervention
Time frame: 24-48 hours after the completion of study intervention
Ventilatory Settings Before and After the Study Intervention
Time frame: 24-48 hours after the completion of study intervention
Proportion of Participants With Liver Injury
Time frame: 24-48 hours after the completion of study intervention
Proportion of Participants With Renal Injury
Time frame: 24-48 hours after the completion of study intervention
Proportion of Participants With Hematological Adverse Events
Time frame: 24-48 hours after the completion of study intervention
Total Number of Days of Mechanical Ventilation
Time frame: from randomization until discharge/40 weeks post menstrual age
Total Number of Days of Need for Supplemental Oxygen
Time frame: from randomization until discharge/40 weeks post menstrual age
Duration of Noninvasive Ventilation
Time frame: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants With Persistence of Ductus-needing Pharmacological Treatment
Time frame: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Requiring Surgical Ligation of PDA
Time frame: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Developing Bronchopulmonary Dysplasia
Time frame: at 36 weeks post menstrual age
Percentage of Infants Requiring Home Oxygen Therapy
Time frame: at discharge/40 weeks post menstrual age
Proportion of Participants Developing Death Before Discharge
Time frame: until discharge/40 weeks post menstrual age
Time to Achieve Full Enteral Feeding
Time frame: from birth until discharge/40 weeks post menstrual age
Total Days on Total Parenteral Nutrition
Time frame: from birth until discharge/40 weeks post menstrual age
Proportion of Participants With Retinopathy of Prematurity
Time frame: from birth until discharge/40 weeks post menstrual age
Proportion of Participants Developing Spontaneous Intestinal Perforation
Time frame: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Developing Necrotizing Enterocolitis
Time frame: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Developing Gastrointestinal Hemorrhage
Time frame: from randomization until discharge/40 weeks post menstrual age
Proportion of Participants Developing Late Onset Sepsis
Time frame: from randomization until discharge/40 weeks post menstrual age
Length of Hospital Stay
Time frame: from birth until discharge/40 weeks post menstrual age
Proportion of Participants With Periventricular Leukomalacia
Time frame: from randomization until discharge/40 weeks post menstrual age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Fabien Eyal, MD study director
University of South Alabama
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 and acetaminophen in people with Patent Ductus Arteriosus and Preterm Infant, run by University of South Alabama 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 10 inclusion and 10 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 30 Apr 2026. 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.
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?
Yes. Results are posted in the registry (first posted 11 May 2021). 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?
Proportion of Participants With Ductus Arteriosus Closure/Constriction (time frame: 24-48 hours after the completion of study intervention). 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 30 Apr 2026; AzTrials last refreshed its copy on 31 Oct 2026.