Ductus Arteriosus, PatentPIVOTALNCT05547165
Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants
A study testing Percutaneous Patent Ductus Arteriosus Closure (PPC), Responsive Management Intervention and Echocardiogram, cardiac in people with Ductus Arteriosus, Patent, run by Nationwide Children's Hospital at 24 sites in United States.
Trial summary
Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. Read more about this study
- Who is it for?
- Ages 7 to 32 days
- Conditions the study is for
- Ductus Arteriosus, Patent
- What is being tested?
- Percutaneous Patent Ductus Arteriosus Closure (PPC), Responsive Management Intervention and Echocardiogram, cardiac
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 24 sitesUnited States
- Study dates
- 21 Feb 2023to 28 Feb 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 7 to 32 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- EPIs born between 22-weeks+0 days (220/7 wks) and 27-weeks+6 days (276/7 wks) gestation, inclusive
- Admitted to a study NICU
- Birth weight ≥700-grams
- Mechanically ventilated at time of consent and randomization
- HSPDA ("PDA Score" ≥6) noted on echocardiogram (ECHO)
- Randomization is able to be performed within 5 days of the qualifying ECHO and when infant is 7-32 days postnatal
Who cannot join
- Clinical Exclusion Criteria
- Life-threatening congenital defects (including congenital heart disease such as aortic coarctation or pulmonary artery stenosis). PDA and small atrial/ventricular septal defects are permitted;
- Congenital lung abnormalities, (e.g. restrictive lung disease);
- Pharyngeal or airway anomalies (tracheal stenosis, choanal atresia);
- Treatment for acute abdominal process (e.g., necrotizing enterocolitis);
- Infants with planned surgery;
Show all 19Show fewer
- Active infection requiring treatment;
- Chromosomal defects (e.g., Trisomy 18);
- Neuromuscular disorders;
- Infants whose parents have chosen to allow natural death (do not resuscitate order) or for whom limitation of intensive care treatment is being considered (e.g. severe intraventricular hemorrhage)
- Physician deems that the infant would not be a Percutaneous PDA Closure candidate due to clinical instability; however, if the infant's clinical status improves before 30-days postnatal and all inclusion criteria are still met, then the infant may be enrolled.
- ECHO-based Exclusion Criteria
- Pulmonary hypertension (defined by ductal right to left shunting for >33% of the cardiac cycle) in which early PDA closure may increase right ventricular afterload and compromise pulmonary and systemic blood flow;
- Evidence of cardiac thrombus that might interfere with device placement;
- PDA diameter larger than 4 mm at the narrowest portion (consistent with FDA-approved instructions for Piccolo™ device use).
- PDA length smaller than 3 mm (consistent with FDA-approved instructions for Piccolo™ device use).
- PDA that does not meet inclusion requirements ("PDA Score" <6).* * If a potential participant is found to have a PDA meeting eligibility requirements on a subsequent ECHO during the required period of 7 - 30 postnatal days of age, they may then be declared eligible to participate and enrolled, provided all other inclusion criteria are met and exclusion criteria are not met.
- Other Exclusion Criteria
- 1. Parents or legal guardian do not speak English or Spanish
Trial locations and contacts
24 sites in 1 country. Contact the study team or a site near you to ask about taking part.
24 sites in 1 country
United States24 sites, 16 recruiting
- Withdrawn
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
- Withdrawn
Children's Hospital Colorado
Aurora, Colorado, 80045
- Recruiting
University of Alabama
Birmingham, Alabama, 35294
Hope Arnold, MD, 225-571-4656, hopearnold@uabmc.edu
Stephen Clark, MD, 205-934-3460, stclark@uabmc.edu
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Philip Levy, MD, philip.levy@childrens.harvard.edu
- Recruiting
Ann and Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
Nicolas Porta, MD, nporta@luriechildrens.org
Alan Nugent, MD, anugent@luriechildrens.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Jonathan Slaughter, MD, Jonathan.Slaughter@nationwidechildrens.org
Carl Backes, MD, Carl.Backes@nationwidechildrens.org
- Recruiting
Medical City Children's Dallas
Dallas, Texas, 75230
Vivian Dimas, MD, vivian.dimas@hcahealthcare.com
Carrie Herbert, MD, Carrie.Herbert@hcahealthcare.com
- Recruiting
UT Southwestern Children's Medical Center of Dallas
Dallas, Texas, 75235
Sushmita Yallapragada, MD, Sushmita.Yallapragada@UTSouthwestern.edu
Suren Reddy, MD, suren.reddy@utsouthwestern.edu
- Recruiting
Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Peter Guyton, MD, PGuyon@mhs.net
Bruce Schulman, MD, Brucesmd@aol.com
- Recruiting
Texas Children's
Houston, Texas, 77030
Sharada Gowda, MD, 732-925-4563, shgowda@bcm.edu
Gary Stapleton, gestaple@texaschildrens.org
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Megha Sharma, MD, MSharma@uams.edu
Sherry Courtney, MD, SECourtney@uams.edu
- Withdrawn
Children's Hospital Los Angeles
Los Angeles, California, 90027
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Evan Zahn, MD, Evan.Zahn@cshs.org
Kurlen Payton, MD, Kurlen.Payton@cshs.org
- Recruiting
Le Bonheur Children's Medical Center
Memphis, Tennessee, 38103
Mark Weems, MD, mweems@uthsc.edu
- Recruiting
Children's Wisconsin
Milwaukee, Wisconsin, 53226
Vijay Karody, MD, vkarody@mcw.edu
Todd Gudausky, MD, dgudausk@mcw.edu
- Withdrawn
University of Minnesota, Masonic Children's Hospital
Minneapolis, Minnesota, 55455
- Withdrawn
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
- Withdrawn
Morgan Stanley Children's Hospital of New York-Presbyterian
New York, New York, 10032
- Recruiting
Orlando Health
Orlando, Florida, 32806
Michael McMahan, MD, Michael.McMahan@orlandohealth.com
Michael Farias, MD, michael.farias@orlandohealth.com
- Withdrawn
Lucille Packard Children's Hospital at Stanford
Palo Alto, California, 94304
- Withdrawn
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
- Recruiting
UC Davis Children's Hospital
Sacramento, California, 95817
Frank Ing, MD, ffing@ucdavis.edu
- Recruiting
Seattle Children's
Seattle, Washington, 98105
Kirti Upadhyay, MD, kupadhya@uw.edu
Brian Morray, MD, brian.morray@seattlechildrens.org
- Recruiting
St. Louis Children's Hospital
St Louis, Missouri, 63110
Daisuke Kobayashi, MD, daisuke@wustl.edu
Andy Glatz, MD, glatz@wustl.edu
About this study
Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. In the womb, the opening (ductus arteriosus) is the normal part of the circulatory system of the baby, but is expected to close at full term birth. If the opening is tiny, the condition can be self-limiting. If not, medications/surgery are options for treatment.
There are two ways to treat patent ductus arteriosus - one is through closure of the opening with an FDA approved device called PICCOLO, the other is through supportive management (medications). No randomized controlled trials have been done previously to see if one of better than the other. Through our PIVOTAL study, the investigators aim to determine is one is indeed better than the other - if it is found that the percutaneous closure with PICCOLO is better, then it would immediately lead to a new standard of care. If not, then the investigators avoid an invasive costly procedure going forward.
- Conditions
- Ductus Arteriosus, Patent
- Being tested
- Percutaneous Patent Ductus Arteriosus Closure (PPC), Responsive Management Intervention, Echocardiogram, cardiac
- Keywords
- PDA
- 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.
Percutaneous Patent Ductus Arteriosus Closure (PPC)Device
Infants in this group will undergo catheter-based PPC closure ≤48 hours following randomization and within 7-days of qualifying ECHO. All participants assigned to PPC will receive the Amplatzer Piccolo™ Occluder which will be implanted within the duct (intraductal placement). The Piccolo™ occluder is approved by the US FDA for this purpose.
Responsive Management InterventionCombination product
Interventional PDA-closure, including PPC or surgical ligation and post-randomization pharmacologic (NSAID or acetaminophen) (enteral or intravenous) PDA treatment, are not allowed unless secondary treatment thresholds (see below) are met. Healthcare decisions for Responsive Management will be made at the discretion of the treatment team, while the infant is carefully monitored for any decline in status that may be attributed to the presence of PDA, in which case, Secondary Intervention (described below) may be considered.
Despite widespread acceptance of responsive PDA management, no consensus definition exists. The following Responsive Management interventions are permitted but not required per clinician discretion: 1) fluid restriction between 120-140 mL/kg/day; 2) diuretics (per local practice); 3) increases in positive end-expiratory pressure (PEEP).
Echocardiogram, cardiacDiagnostic test
An echocardiogram, also known as "ECHO", is an ultrasound image of the heart. Echocardiography is a common test used for the diagnosis and management of cardiac diseases or conditions.
| Study group | Role | What they receive |
|---|---|---|
| Primary Comparator | Active comparator | Interventional groups that subject will be randomly assigned to include Percutaneous Patent Ductus Arteriosus Closure (PPC) or Responsive Management. Those assigned to PPC will undergo active intervention to close a hemodynamically significant patent ductus arteriosus (HSPDA) whereas those assigned to Responsive Management will be treated to manage the symptoms of the HSPDA and permit natural closure over time. Receives: Device: Percutaneous Patent Ductus Arteriosus Closure (PPC); Combination Product: Responsive Management Intervention; Diagnostic Test: Echocardiogram, cardiac |
| Secondary Intervention | Other | Sub-group of patients initially randomized to Responsive Management who may suffer a decline in health status that can be attributed to the presence of a hemodynamically significant patent ductus arteriosus (HSPDA). These patients, upon meeting pre-specified clinical criteria, will undergo active treatment via Percutaneous Patent Ductus Arteriosus Closure (PPC) as in the active comparator arm. Receives: Device: Percutaneous Patent Ductus Arteriosus Closure (PPC); Diagnostic Test: Echocardiogram, cardiac |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of days free of ventilatory support requirement (ventilator-free days; VFDs)
Ventilator free days (VFDs) are defined as the number of days that a subject is alive and free from mechanical ventilatory support. VFDs are an established respiratory outcome measure in pediatric clinical trials, and are a strong predictor of short-term and longer-term oucomes, including length of neonatal intensive care unit (NICU) stay, morbidities, and mortality.
Measured: 30 days post-randomization
Secondary outcomes (21)
Positive-pressure dependency or death
A composite outcome measure (yes/no), positive pressure dependency at 36 weeks post-menstrual age (PMA) is an indicator of chronic lung disease (CLD), the most common and serious respiratory complication of prematurity. Both invasive and non-invasive positive pressure ventilation at 36 weeks PMA is associated with long-term respiratory and neurodevelopmental impairment.
Measured: 36 weeks post-menstrual age
Diagnosis of pulmonary hypertension or death
A compositve binary outcome measure (yes/no), diagnosis of pulmonary hypertension will be determined by cardiac echocardiogram at 36 weeks post-menstrual age. Diagnosis of pulmonary hypertension is an indicator of increased pulmonary vasculature resistance, a marker for increased morbidity and mortality among infants with chronic lung disease.
Measured: 36 weeks post-menstrual age
Total days on mechanical ventilation
The total number of days (continuous variable) a study subject requires any use of invasive mechanical ventilatory support within a 24-hour calendar day.
Measured: 4 months corrected age
Days requiring positive-pressure assisted breathing
The sum of days the study subject requires either invasive or non-invasive positive pressure assisted ventilation within a 24 hour calendar day.
Measured: Randomization through 4 months corrected age
Days on supplemental oxygen
Total number of days the study subject requires supplemental oxygen. The subject may be on either invasive or non-invasive ventilatory support during this time. The subject must be free from supplemental oxygen use for a period of at least 24 hours to interrupt or cease counting.
Measured: Randomization through 4 months corrected age
Time to death
A continuous measure, in days, of the time from a study subject's randomization to expiration, if this occurs.
Measured: Randomization through 4 months corrected age
Diagnosis of cardiac dysfunction
A diagnosis of left-ventricular output by echocardiography (ECHO) at 36 weeks post-menstrual age.
Measured: 36 weeks post-menstrual age
Abnormal cardiac remodeling
Finding of left-ventricular end-diastolic volume (LV EDV) >97% on echocardiography (ECHO) at 36 weeks post-menstrual age.
Measured: 36 weeks post-menstrual age
General Movements Assessment (GMA)
The General Movements Assessment (GMA) is a standardized video-based neurological exam to evaluate the presence of "fidgety" versus "absent fidgety" and "cramped-synchronized" versus "non cramped-synchronized" movement patterns at 34 - 36 weeks post-menstrual age. It is used to assist in the diagnosis of impaired motor neurodevelopment and cerebral palsy.
Measured: 34 - 36 weeks post-menstrual age
Need for rescue intervention
Recording of incidence of need for study subjects randomized to Responsive Management to undergo Percutaneous Patent Ductus Arteriosus Closure (PPC) due to decline in health status.
Measured: Randomization through 4 months corrected age
Hammersmith Neonatal Neurological Examination (HNNE)
The HNNE is a standardized neurological examination of 34 items to evaluate tone, motor patterns, spontaneous movements, reflexes, visual and auditory attention, and behavior.
Measured: 34 - 36 weeks post-menstrual age
Hammersmith Infant Neurological Examination (HINE)
The HINE is similar to the HNNE, used to assess neurological function at 3 - 24 months of age, including cranial nerve function, movements, reflexes, protective reactions and behavior, and age-dependent evaluation of gross and fine-motor function.
Measured: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Low Registration Domain)
Caregiver questionnaire responses to determine if their infant appropriately processes and responds to environmental stimuli, versus missing or taking longer to respond ("Low Registration"). There are 13 items with scores of 13 - 65 possible; scores of 42 - 51 are considered "Typical performance".
Measured: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Sensation Seeking Domain)
Caregiver questionnaire responses to determine if their infant is hyposensitive, seeking additional sensory stimulation. There are 6 items with scores of 6 - 30 possible; scores of 7 - 15 are considered "Typical performance".
Measured: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Sensory Sensitivity Domain)
Caregiver questionnaire responses to determine if their infant responds readily to sensory stimulation, without actively avoiding it. There are 12 items with scores of 12 - 60 possible; scores of 45 - 57 are considered "Typical performance)
Measured: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Sensation Avoiding Domain)
Caregiver questionnaire responses to determine if their infant avoids sensory stimulation. There are 5 items with scores of 5 - 25 possible; scores of 19 - 25 are considered "Typical performance".
Measured: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Low Threshold Domain)
Caregiver questionnaire responses which are the sum of the Sensory Sensitivity and Sensation Avoiding domains). Summed scores of 15 - 85 are possible; summed scores of 64 - 81 are considered "Typical performance".
Measured: 3 - 4 months of corrected age
Baby Care Questionnaire (BCQ)
The BCQ is another caregiver-based questionnaire for parental perspectives of an infant's feeding and sleeping habits. It is used as an evaluation of a parent's reliance upon structure / routines and attunement (dependence upon infant's cues).
Measured: 3 - 4 months of corrected age
Mother-Infant Bonding Scale (MIBS)
The MIBS is an 8-item questionnaire to evaluate a mother's bondedness towards her infant. Responses are scored from 0 to 3 for each item, with a total possible range of 0 - 24. Lower scores indicate more favorable outcomes for mother-infant bondedness, whereas higher scores indicate the potential for difficulties.
Measured: 3 - 4 months of corrected age
Type and incidence of any adverse event
Reporting of type and frequency of any adverse event that occurs during percutaneous closure procedures, and post-procedurally that may be related to the intervention.
Measured: 3 - 4 months of corrected age
Type and incidence of serious adverse event
Reporting of type and frequency of any serious adverse event (e.g., potentially life-threatening change in status) that occurs during percutaneous closure procedures, and post-procedurally that may be related to the intervention.
Measured: 3 - 4 months of corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2022
- Study start21 Feb 2023
- Primary completion28 Feb 2026 (estimated)
- Study completion28 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Ductus Arteriosus, PatentStudies of the same condition, open and under way.
- More trials run by Nationwide Children's 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Abbott, University of Pittsburgh, University of Bristol, Dartmouth College, University of Iowa, Emory University, Cedars-Sinai Medical Center, Children's Hospital Los Angeles, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Carl Backes, MD, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05547165
- Sponsor's protocol ID
- 00002501
- Other IDs
- UG3HL161338
- Acronym
- PIVOTAL
- Status last verified
- Mar 2025
- First submitted
- 30 Aug 2022
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Benitz WE; Committee on Fetus and Newborn, American Academy of Pediatrics. Patent Ductus Arteriosus in Preterm Infants. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3730. Epub 2015 Dec 15.
PubMed 26672023Benitz WE. Patent ductus arteriosus: to treat or not to treat? Arch Dis Child Fetal Neonatal Ed. 2012 Mar;97(2):F80-2. doi: 10.1136/archdischild-2011-300381. Epub 2011 Dec 15.
PubMed 22174019Liebowitz M, Katheria A, Sauberan J, Singh J, Nelson K, Hassinger DC, Aucott SW, Kaempf J, Kimball A, Fernandez E, Carey WA, Perez J, Serize A, Wickremasinghe A, Dong L, Derrick M, Wolf IS, Heuchan AM, Sankar M, Bulbul A, Clyman RI; PDA-TOLERATE (PDA: TOLEave it alone or Respond And Treat Early) Trial Investigators. Lack of Equipoise in the PDA-TOLERATE Trial: A Comparison of Eligible Infants Enrolled in the Trial and Those Treated Outside the Trial. J Pediatr. 2019 Oct;213:222-226.e2. doi: 10.1016/j.jpeds.2019.05.049. Epub 2019 Jun 27.
PubMed 31255386Donovan JL, Rooshenas L, Jepson M, Elliott D, Wade J, Avery K, Mills N, Wilson C, Paramasivan S, Blazeby JM. Optimising recruitment and informed consent in randomised controlled trials: the development and implementation of the Quintet Recruitment Intervention (QRI). Trials. 2016 Jun 8;17(1):283. doi: 10.1186/s13063-016-1391-4.
PubMed 27278130Wilson C, Rooshenas L, Paramasivan S, Elliott D, Jepson M, Strong S, Birtle A, Beard DJ, Halliday A, Hamdy FC, Lewis R, Metcalfe C, Rogers CA, Stein RC, Blazeby JM, Donovan JL. Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework. Trials. 2018 Jan 19;19(1):50. doi: 10.1186/s13063-017-2413-6.
PubMed 29351790Donovan JL, Lane JA, Peters TJ, Brindle L, Salter E, Gillatt D, Powell P, Bollina P, Neal DE, Hamdy FC; ProtecT Study Group. Development of a complex intervention improved randomization and informed consent in a randomized controlled trial. J Clin Epidemiol. 2009 Jan;62(1):29-36. doi: 10.1016/j.jclinepi.2008.02.010. Epub 2008 Jul 10.
PubMed 18619811Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1415-1424. doi: 10.1056/NEJMoa1606220. Epub 2016 Sep 14.
PubMed 27626136Rooshenas L, Scott LJ, Blazeby JM, Rogers CA, Tilling KM, Husbands S, Conefrey C, Mills N, Stein RC, Metcalfe C, Carr AJ, Beard DJ, Davis T, Paramasivan S, Jepson M, Avery K, Elliott D, Wilson C, Donovan JL; By-Band-Sleeve study group; CSAW study group; HAND-1 study group; Optima prelim study group; Romio feasibility study group. The QuinteT Recruitment Intervention supported five randomized trials to recruit to target: a mixed-methods evaluation. J Clin Epidemiol. 2019 Feb;106:108-120. doi: 10.1016/j.jclinepi.2018.10.004. Epub 2018 Oct 16.
PubMed 30339938Donovan JL, Paramasivan S, de Salis I, Toerien M. Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials. Trials. 2014 Jan 6;15:5. doi: 10.1186/1745-6215-15-5.
PubMed 24393291Rooshenas L, Elliott D, Wade J, Jepson M, Paramasivan S, Strong S, Wilson C, Beard D, Blazeby JM, Birtle A, Halliday A, Rogers CA, Stein R, Donovan JL; ACST-2 study group; By-Band-Sleeve study group; Chemorad study group; CSAW study group; Optima prelim study group; POUT study group. Conveying Equipoise during Recruitment for Clinical Trials: Qualitative Synthesis of Clinicians' Practices across Six Randomised Controlled Trials. PLoS Med. 2016 Oct 18;13(10):e1002147. doi: 10.1371/journal.pmed.1002147. eCollection 2016 Oct.
PubMed 27755555Mills N, Donovan JL, Wade J, Hamdy FC, Neal DE, Lane JA. Exploring treatment preferences facilitated recruitment to randomized controlled trials. J Clin Epidemiol. 2011 Oct;64(10):1127-36. doi: 10.1016/j.jclinepi.2010.12.017. Epub 2011 Apr 7.
PubMed 21477994Jepson M, Elliott D, Conefrey C, Wade J, Rooshenas L, Wilson C, Beard D, Blazeby JM, Birtle A, Halliday A, Stein R, Donovan JL; CSAW study group; Chemorad study group; POUT study group; ACST-2 study group; OPTIMA prelim study group. An observational study showed that explaining randomization using gambling-related metaphors and computer-agency descriptions impeded randomized clinical trial recruitment. J Clin Epidemiol. 2018 Jul;99:75-83. doi: 10.1016/j.jclinepi.2018.02.018. Epub 2018 Mar 2.
PubMed 29505860Donovan JL, de Salis I, Toerien M, Paramasivan S, Hamdy FC, Blazeby JM. The intellectual challenges and emotional consequences of equipoise contributed to the fragility of recruitment in six randomized controlled trials. J Clin Epidemiol. 2014 Aug;67(8):912-20. doi: 10.1016/j.jclinepi.2014.03.010. Epub 2014 May 5.
PubMed 24811157Rooshenas L, Paramasivan S, Jepson M, Donovan JL. Intensive Triangulation of Qualitative Research and Quantitative Data to Improve Recruitment to Randomized Trials: The QuinteT Approach. Qual Health Res. 2019 Apr;29(5):672-679. doi: 10.1177/1049732319828693. Epub 2019 Feb 22.
PubMed 30791819Coyne IT. Sampling in qualitative research. Purposeful and theoretical sampling; merging or clear boundaries? J Adv Nurs. 1997 Sep;26(3):623-30. doi: 10.1046/j.1365-2648.1997.t01-25-00999.x.
PubMed 9378886
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants
- ClinicalTrials.gov ID
- NCT05547165
- Acronym / sponsor ID
- PIVOTAL / 00002501
- Conditions
- Ductus Arteriosus, Patent
- Keywords
- PDA
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Abbott, University of Pittsburgh, University of Bristol, Dartmouth College, University of Iowa, Emory University, Cedars-Sinai Medical Center, Children's Hospital Los Angeles, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 21 Feb 2023 (actual)
- Primary completion
- 28 Feb 2026 (estimated)
- Study completion
- 28 Feb 2026 (estimated)
- First posted
- 21 Sep 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.
Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. In the womb, the opening (ductus arteriosus) is the normal part of the circulatory system of the baby, but is expected to close at full term birth. If the opening is tiny, the condition can be self-limiting. If not, medications/surgery are options for treatment.
There are two ways to treat patent ductus arteriosus - one is through closure of the opening with an FDA approved device called PICCOLO, the other is through supportive management (medications). No randomized controlled trials have been done previously to see if one of better than the other. Through our PIVOTAL study, the investigators aim to determine is one is indeed better than the other - if it is found that the percutaneous closure with PICCOLO is better, then it would immediately lead to a new standard of care. If not, then the investigators avoid an invasive costly procedure going forward.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Primary Comparator | Active comparator | Device: Percutaneous Patent Ductus Arteriosus Closure (PPC), Combination Product: Responsive Management Intervention, Diagnostic Test: Echocardiogram, cardiacInterventional groups that subject will be randomly assigned to include Percutaneous Patent Ductus Arteriosus Closure (PPC) or Responsive Management. Those assigned to PPC will undergo active intervention to close a hemodynamically significant patent ductus arteriosus (HSPDA) whereas those assigned to Responsive Management will be treated to manage the symptoms of the HSPDA and permit natural closure over time. |
| Secondary Intervention | Other | Device: Percutaneous Patent Ductus Arteriosus Closure (PPC), Diagnostic Test: Echocardiogram, cardiacSub-group of patients initially randomized to Responsive Management who may suffer a decline in health status that can be attributed to the presence of a hemodynamically significant patent ductus arteriosus (HSPDA). These patients, upon meeting pre-specified clinical criteria, will undergo active treatment via Percutaneous Patent Ductus Arteriosus Closure (PPC) as in the active comparator arm. |
Who may qualify
- Ages
- 7 to 32 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- EPIs born between 22-weeks+0 days (220/7 wks) and 27-weeks+6 days (276/7 wks) gestation, inclusive
- Admitted to a study NICU
- Birth weight ≥700-grams
- Mechanically ventilated at time of consent and randomization
- HSPDA ("PDA Score" ≥6) noted on echocardiogram (ECHO)
Key exclusion criteria (19 listed)
- Clinical Exclusion Criteria
- Life-threatening congenital defects (including congenital heart disease such as aortic coarctation or pulmonary artery stenosis). PDA and small atrial/ventricular septal defects are permitted;
- Congenital lung abnormalities, (e.g. restrictive lung disease);
- Pharyngeal or airway anomalies (tracheal stenosis, choanal atresia);
- Treatment for acute abdominal process (e.g., necrotizing enterocolitis);
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 |
|---|---|---|
| Percutaneous Patent Ductus Arteriosus Closure (PPC)Infants in this group will undergo catheter-based PPC closure ≤48 hours following randomization and within 7-days of qualifying ECHO. All participants assigned to PPC will receive the Amplatzer Piccolo™ Occluder which will be implanted within the duct (intraductal placement). The Piccolo™ occluder is approved by the US FDA for this purpose. | Device | Primary Comparator, Secondary Intervention |
| Responsive Management InterventionInterventional PDA-closure, including PPC or surgical ligation and post-randomization pharmacologic (NSAID or acetaminophen) (enteral or intravenous) PDA treatment, are not allowed unless secondary treatment thresholds (see below) are met. Healthcare decisions for Responsive Management will be made at the discretion of the treatment team, while the infant is carefully monitored for any decline in status that may be attributed to the presence of PDA, in which case, Secondary Intervention (described below) may be considered. Despite widespread acceptance of responsive PDA management, no consensus definition exists. The following Responsive Management interventions are permitted but not required per clinician discretion: 1) fluid restriction between 120-140 mL/kg/day; 2) diuretics (per local practice); 3) increases in positive end-expiratory pressure (PEEP). | Combination product | Primary Comparator |
| Echocardiogram, cardiacAn echocardiogram, also known as "ECHO", is an ultrasound image of the heart. Echocardiography is a common test used for the diagnosis and management of cardiac diseases or conditions. | Diagnostic test | Primary Comparator, Secondary Intervention |
Primary outcome
Number of days free of ventilatory support requirement (ventilator-free days; VFDs)
Time frame: 30 days post-randomization
Ventilator free days (VFDs) are defined as the number of days that a subject is alive and free from mechanical ventilatory support. VFDs are an established respiratory outcome measure in pediatric clinical trials, and are a strong predictor of short-term and longer-term oucomes, including length of neonatal intensive care unit (NICU) stay, morbidities, and mortality.
21 secondary outcomes
Positive-pressure dependency or death
Time frame: 36 weeks post-menstrual age
Diagnosis of pulmonary hypertension or death
Time frame: 36 weeks post-menstrual age
Total days on mechanical ventilation
Time frame: 4 months corrected age
Days requiring positive-pressure assisted breathing
Time frame: Randomization through 4 months corrected age
Days on supplemental oxygen
Time frame: Randomization through 4 months corrected age
Time to death
Time frame: Randomization through 4 months corrected age
Diagnosis of cardiac dysfunction
Time frame: 36 weeks post-menstrual age
Abnormal cardiac remodeling
Time frame: 36 weeks post-menstrual age
General Movements Assessment (GMA)
Time frame: 34 - 36 weeks post-menstrual age
Need for rescue intervention
Time frame: Randomization through 4 months corrected age
Hammersmith Neonatal Neurological Examination (HNNE)
Time frame: 34 - 36 weeks post-menstrual age
Hammersmith Infant Neurological Examination (HINE)
Time frame: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Low Registration Domain)
Time frame: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Sensation Seeking Domain)
Time frame: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Sensory Sensitivity Domain)
Time frame: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Sensation Avoiding Domain)
Time frame: 3 - 4 months of corrected age
Infant/Toddler Sensory Profile (Low Threshold Domain)
Time frame: 3 - 4 months of corrected age
Baby Care Questionnaire (BCQ)
Time frame: 3 - 4 months of corrected age
Mother-Infant Bonding Scale (MIBS)
Time frame: 3 - 4 months of corrected age
Type and incidence of any adverse event
Time frame: 3 - 4 months of corrected age
Type and incidence of serious adverse event
Time frame: 3 - 4 months of corrected age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Background: PubMed 26672023Benitz WE; Committee on Fetus and Newborn, American Academy of Pediatrics. Patent Ductus Arteriosus in Preterm Infants. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3730. Epub 2015 Dec 15.
- Background: PubMed 22174019Benitz WE. Patent ductus arteriosus: to treat or not to treat? Arch Dis Child Fetal Neonatal Ed. 2012 Mar;97(2):F80-2. doi: 10.1136/archdischild-2011-300381. Epub 2011 Dec 15.
- Background: PubMed 31255386Liebowitz M, Katheria A, Sauberan J, Singh J, Nelson K, Hassinger DC, Aucott SW, Kaempf J, Kimball A, Fernandez E, Carey WA, Perez J, Serize A, Wickremasinghe A, Dong L, Derrick M, Wolf IS, Heuchan AM, Sankar M, Bulbul A, Clyman RI; PDA-TOLERATE (PDA: TOLEave it alone or Respond And Treat Early) Trial Investigators. Lack of Equipoise in the PDA-TOLERATE Trial: A Comparison of Eligible Infants Enrolled in the Trial and Those Treated Outside the Trial. J Pediatr. 2019 Oct;213:222-226.e2. doi: 10.1016/j.jpeds.2019.05.049. Epub 2019 Jun 27.
- Background: PubMed 27278130Donovan JL, Rooshenas L, Jepson M, Elliott D, Wade J, Avery K, Mills N, Wilson C, Paramasivan S, Blazeby JM. Optimising recruitment and informed consent in randomised controlled trials: the development and implementation of the Quintet Recruitment Intervention (QRI). Trials. 2016 Jun 8;17(1):283. doi: 10.1186/s13063-016-1391-4.
- Background: PubMed 29351790Wilson C, Rooshenas L, Paramasivan S, Elliott D, Jepson M, Strong S, Birtle A, Beard DJ, Halliday A, Hamdy FC, Lewis R, Metcalfe C, Rogers CA, Stein RC, Blazeby JM, Donovan JL. Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework. Trials. 2018 Jan 19;19(1):50. doi: 10.1186/s13063-017-2413-6.
- Background: PubMed 18619811Donovan JL, Lane JA, Peters TJ, Brindle L, Salter E, Gillatt D, Powell P, Bollina P, Neal DE, Hamdy FC; ProtecT Study Group. Development of a complex intervention improved randomization and informed consent in a randomized controlled trial. J Clin Epidemiol. 2009 Jan;62(1):29-36. doi: 10.1016/j.jclinepi.2008.02.010. Epub 2008 Jul 10.
- Background: PubMed 27626136Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1415-1424. doi: 10.1056/NEJMoa1606220. Epub 2016 Sep 14.
- Background: PubMed 30339938Rooshenas L, Scott LJ, Blazeby JM, Rogers CA, Tilling KM, Husbands S, Conefrey C, Mills N, Stein RC, Metcalfe C, Carr AJ, Beard DJ, Davis T, Paramasivan S, Jepson M, Avery K, Elliott D, Wilson C, Donovan JL; By-Band-Sleeve study group; CSAW study group; HAND-1 study group; Optima prelim study group; Romio feasibility study group. The QuinteT Recruitment Intervention supported five randomized trials to recruit to target: a mixed-methods evaluation. J Clin Epidemiol. 2019 Feb;106:108-120. doi: 10.1016/j.jclinepi.2018.10.004. Epub 2018 Oct 16.
- Background: PubMed 24393291Donovan JL, Paramasivan S, de Salis I, Toerien M. Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials. Trials. 2014 Jan 6;15:5. doi: 10.1186/1745-6215-15-5.
- Background: PubMed 27755555Rooshenas L, Elliott D, Wade J, Jepson M, Paramasivan S, Strong S, Wilson C, Beard D, Blazeby JM, Birtle A, Halliday A, Rogers CA, Stein R, Donovan JL; ACST-2 study group; By-Band-Sleeve study group; Chemorad study group; CSAW study group; Optima prelim study group; POUT study group. Conveying Equipoise during Recruitment for Clinical Trials: Qualitative Synthesis of Clinicians' Practices across Six Randomised Controlled Trials. PLoS Med. 2016 Oct 18;13(10):e1002147. doi: 10.1371/journal.pmed.1002147. eCollection 2016 Oct.
- Background: PubMed 21477994Mills N, Donovan JL, Wade J, Hamdy FC, Neal DE, Lane JA. Exploring treatment preferences facilitated recruitment to randomized controlled trials. J Clin Epidemiol. 2011 Oct;64(10):1127-36. doi: 10.1016/j.jclinepi.2010.12.017. Epub 2011 Apr 7.
- Background: PubMed 29505860Jepson M, Elliott D, Conefrey C, Wade J, Rooshenas L, Wilson C, Beard D, Blazeby JM, Birtle A, Halliday A, Stein R, Donovan JL; CSAW study group; Chemorad study group; POUT study group; ACST-2 study group; OPTIMA prelim study group. An observational study showed that explaining randomization using gambling-related metaphors and computer-agency descriptions impeded randomized clinical trial recruitment. J Clin Epidemiol. 2018 Jul;99:75-83. doi: 10.1016/j.jclinepi.2018.02.018. Epub 2018 Mar 2.
- Individual participant dataSharing planned: No
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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.
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Percutaneous Patent Ductus Arteriosus Closure (PPC), Responsive Management Intervention and Echocardiogram, cardiac in people with Ductus Arteriosus, Patent, run by Nationwide Children's Hospital at 24 sites 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 6 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carl H Backes (16143556729, carl.backes@nationwidechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of days free of ventilatory support requirement (ventilator-free days; VFDs) (time frame: 30 days post-randomization). 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 NCT05547165, which also lists 28 linked publications.
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 Mar 2025.