PPC vs Observation for Patent Ductus Arteriosus in Infants

(PIVOTAL Trial)

Recruiting at 20 trial locations

Overseen By Carl H Backes

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Nationwide Children's Hospital

Disqualifiers: Congenital defects, Lung abnormalities, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 weeks post-menstrual age

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to treat patent ductus arteriosus (PDA) in infants born prematurely. PDA occurs when an opening near the heart fails to close after birth. The trial compares two treatments: one uses a device called PICCOLO (or the PICCOLO Occluder) to close the opening, while the other uses medications to manage symptoms and allow natural closure. Infants born preterm, who are on a ventilator, and have a specific heart condition identified by ultrasound may be suitable candidates for this trial. The goal is to determine which method is more effective, potentially changing future PDA treatment. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could redefine treatment standards for PDA in preterm infants.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. It is best to consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Amplatzer Piccolo Occluder is generally safe for treating patent ductus arteriosus (PDA) in infants. Studies indicate it successfully closes the PDA in over 95% of cases, with most patients experiencing no serious complications. The device is particularly effective for small infants weighing between 700 grams and 2 kilograms.

Data further support the device's safety, showing that more than 95% of patients survive at least three years after the procedure. This suggests that the device is not only effective but also well-tolerated over time.

For those considering supportive management with medications, while specific data isn't provided, this approach is generally seen as less invasive and may allow the PDA to close on its own.

In summary, both treatment options are considered safe, but the Piccolo device has strong evidence of effectiveness and a low risk of serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for patent ductus arteriosus (PDA) in infants because they offer a tailored approach based on the severity of the condition. Unlike traditional treatments, which often involve medication or surgery, Percutaneous Patent Ductus Arteriosus Closure (PPC) directly closes the PDA in a minimally invasive way, potentially reducing recovery time and complications. Additionally, the Responsive Management strategy allows for natural closure while managing symptoms, reserving PPC for cases where health declines, offering a personalized treatment path. This flexibility in treatment could lead to better outcomes for infants with PDA.

What evidence suggests that this trial's treatments could be effective for patent ductus arteriosus?

Research has shown that the PICCOLO device, which participants in this trial may receive, effectively closes a heart condition called patent ductus arteriosus (PDA) in infants. One study found that the PDA was successfully closed in all patients after 3 years. The device was placed successfully in 95.5% of cases, and more than 95% of the infants survived. The device works especially well for infants weighing between 700 grams and 2 kilograms, with few serious complications. These findings suggest that the PICCOLO device is a reliable option for treating PDA in infants. Meanwhile, another group in this trial will receive Responsive Management, which involves managing the symptoms of PDA and allowing natural closure over time. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for preterm infants with Patent Ductus Arteriosus (PDA), a heart condition present at birth. Eligible infants must be in the NICU, on mechanical ventilation, and between 7-32 days old with a birth weight of ≥700 grams. They should have a specific PDA severity score on an echocardiogram but no chromosomal defects, neuromuscular disorders, congenital lung abnormalities or life-threatening conditions.

Inclusion Criteria

My baby can be enrolled in the study within 5 days of their heart test, and they are 7-32 days old.

My baby was born between 22 and 27 weeks of pregnancy.

You weighed at least 700 grams (about 1.5 pounds) at birth.

Exclusion Criteria

My infant is under a do not resuscitate order or we are considering limiting intensive care.

I have a genetic condition like Trisomy 18.

I have a blood clot in my heart that could affect medical device placement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to either Percutaneous Patent Ductus Arteriosus Closure (PPC) or Responsive Management. Those in the PPC group undergo active intervention, while those in the Responsive Management group receive supportive care.

Up to 36 weeks post-menstrual age

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cardiac function and neurodevelopmental outcomes.

4 months corrected age

Extension

Participants may continue to be monitored for long-term outcomes, including neurodevelopmental assessments and respiratory support requirements.

Up to 4 months corrected age

What Are the Treatments Tested in This Trial?

Interventions

• PICCOLO
• Responsive Management Intervention

Trial Overview The study compares two treatments for PDA: percutaneous closure using the PICCOLO device versus supportive management with medications. It's designed to see which method is more effective for these low-weight infants and could potentially set new care standards.

How Is the Trial Designed?

Group I: Secondary Intervention Experimental Treatment 2 Interventions

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.

Group II: Primary Comparator Active Control 3 Interventions

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.

PICCOLO is already approved in United States, European Union for the following indications:

Approved in United States as PICCOLO Occluder for:

• Closure of patent ductus arteriosus in preterm infants

Approved in European Union as PICCOLO Occluder for:

• Closure of patent ductus arteriosus in preterm infants

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Abbott

Industry Sponsor

Trials

760

Recruited

489,000+

Dr. Etahn Korngold

Abbott

Chief Medical Officer

MD, Harvard Medical School

Robert B. Ford

Abbott

Chief Executive Officer since 2020

Bachelor's degree from Boston College, MBA from UC Berkeley, Haas School of Business

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

University of Bristol

Collaborator

Trials

114

Recruited

25,030,000+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dartmouth College

Collaborator

Trials

93

Recruited

1,415,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

Published Research Related to This Trial

In a study of 201 premature infants with a patent ductus arteriosus (PDA), 47% experienced spontaneous closure by 12 months, and 58% by 18 months, indicating a significant rate of natural resolution over time.

The study also found that 8.4% of infants required assisted closure through surgical methods, and there was a notable incidence of serious adverse events, highlighting the need for careful monitoring of these infants after discharge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Rate of Spontaneous Closure in Premature Infants Discharged with a Patent Ductus Arteriosus: A Multicenter Prospective Study. Tolia, VN., Powers, GC., Kelleher, AS., et al.[2022]

In a study of 408 infants weighing less than 6 kg who underwent transcatheter patent ductus arteriosus (PDA) closure, a high success rate of 92% was achieved without major complications, indicating that this procedure is safe for smaller patients.

While the procedure is effective, the study noted a higher embolization rate (5%) compared to larger patients, suggesting that careful assessment of duct morphology and device retrievability is crucial when considering transcatheter closure versus surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome after transcatheter occlusion of patent ductus arteriosus in infants less than 6 kg: A national study from United Kingdom and Ireland. Kang, SL., Jivanji, S., Mehta, C., et al.[2018]

A 1.4 kg infant successfully underwent transcatheter closure of a patent ductus arteriosus using the Amplatzer Piccolo occluder, demonstrating the feasibility of this procedure in very small infants.

The procedure was adapted to a transjugular venous approach due to an unexpected anatomical challenge (interrupted inferior vena cava), highlighting the importance of flexibility in surgical techniques for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transjugular venous approach for Piccolo patent ductus arteriosus closure in a 1.4 kg infant. Herron, C., Forbes, TJ., Kobayashi, D.[2022]

Transcatheter closure of patent ductus arteriosus (PDA) using the Amplatzer Piccolo Occluder is safe and effective, with successful closure in all cases analyzed from 147 preterm infants.

Infants who underwent catheter closure had a shorter duration of mechanical ventilation (3 days) compared to those who had surgical closure (5 days), and those treated earlier (before 4 weeks of age) were discharged home sooner, indicating potential benefits of this less invasive approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved ventilation in premature babies after transcatheter versus surgical closure of patent ductus arteriosus. Regan, W., Benbrik, N., Sharma, SR., et al.[2021]

The Amplatzer Piccolo Occluder demonstrated a high success rate of 99.1% in closing patent ductus arteriosus in a study of 645 patients, including premature infants, with a mean follow-up of 20.4 months.

The device showed a low complication rate, with only 2% experiencing device embolization and minimal serious adverse events, indicating it is a safe and effective option for ductus closure across various age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Piccolo in transcatheter PDA closure multi-centre study from premature to adolescent children. Baspinar, O., Narin, N., Baykan, A., et al.[2023]

The Amplatzer Piccolo™ Occluder achieved a high implant success rate of 95.5% and demonstrated 100% closure of the patent ductus arteriosus (PDA) in patients followed for 3 years, indicating its efficacy in treating this condition in premature infants.

The study reported a survival rate of over 95% with low rates of serious complications, confirming the safety of the device and procedure, as no deaths were linked to the device or procedure-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3-year follow-up of a prospective, multicenter study of the Amplatzer Piccolo™ Occluder for transcatheter patent ductus arteriosus closure in children ≥ 700 grams. Morray, BH., Sathanandam, SK., Forbes, T., et al.[2023]

In a study of 1389 infants born before 28 weeks of gestation, those who underwent surgical ligation for patent ductus arteriosus had significantly higher odds of major morbidities and neurodevelopmental impairment compared to those treated pharmacologically.

The study revealed a notable variation in treatment practices between Swiss perinatal centers, with higher rates of surgical ligation in centers performing more than 10% of these procedures, which was associated with increased risks of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes for Infants Born in Perinatal Centers Performing Fewer Surgical Ligations for Patent Ductus Arteriosus: A Swiss Population-Based Study. Adams, M., Schulzke, SM., Natalucci, G., et al.[2021]

Spontaneous closure rates of the ductus arteriosus in preterm infants vary significantly, with the lowest rates observed in those born before 28 weeks gestation or weighing less than 1,000 g, indicating that gestational age and birth weight are critical factors in treatment decisions.

The likelihood of spontaneous closure increases for at least a week after birth, suggesting that delaying treatment for patent ductus arteriosus (PDA) may be beneficial for infants who show signs of closure, emphasizing the need for better prediction methods for individual cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous Closure of the Ductus Arteriosus in Preterm Infants: A Systematic Review. de Klerk, JCA., Engbers, AGJ., van Beek, F., et al.[2023]

The Amplatzer Piccolo Occluder demonstrated a high implant success rate of 95.5% overall and 99% in patients weighing ≤2 kg, achieving a 99.4% closure rate of patent ductus arteriosus (PDA) at 6 months.

The device was found to be safe, with only four major complications reported among 200 patients, and no significant pulmonary artery obstructions, indicating it is a viable option for treating PDA in premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amplatzer Piccolo Occluder clinical trial for percutaneous closure of the patent ductus arteriosus in patients ≥700 grams. Sathanandam, SK., Gutfinger, D., O'Brien, L., et al.[2021]

Percutaneous patent ductus arteriosus closure in infants weighing ≤1.5 kg has a high technical success rate of 96%, indicating that this procedure is effective even in very small patients.

While the overall incidence of adverse events (AEs) was 27%, major AEs were relatively low at 8%, and the procedure was associated with a low mortality rate of 2%, primarily occurring in the smallest infants (<0.8 kg).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Closure of Patent Ductus Arteriosus in Infants 1.5 kg or Less: A Meta-Analysis. Bischoff, AR., Jasani, B., Sathanandam, SK., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37587183/

3-year follow-up of a prospective, multicenter study of the ... Results: The implant success rate was 95.5% (191/200). At 3 years, PDA closure was observed in 100% (33/33) of patients. Survival was >95% with 9 reported ...

2. nature.com nature.com/articles/s41372-023-01741-1

3-year follow-up of a prospective, multicenter study of the ... This follow-up study demonstrates high rates of PDA closure, low serious complication rates, and survival > 95% at 3 years.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32433821/

Amplatzer Piccolo Occluder clinical trial for percutaneous ... This study supports the safety and effectiveness of the Amplatzer Piccolo Occluder, particularly in patients between 700 g and 2 kg.

4. abbott.mediaroom.com abbott.mediaroom.com/2022-09-08-Three-Year-Data-on-Worlds-Smallest-Heart-Device-Show-Benefits-of-Fixing-Holes-in-Newborn-Hearts-Without-Surgery

Three-Year Data on World's Smallest Heart Device Show ... The data confirm that the Amplatzer Piccolo Occluder can offer high success rates in terms of PDA closure while offering low adverse event rates ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04205877?term=AREA%5BConditionSearch%5D(%22Ductus%20Arteriosus,%20Patent%22)&rank=3

Study Details | NCT04205877 | The U.S. PDA Registry Device utilized for closure of PDA, study is to help assure continued safety and effectiveness of FDA approved Amplatzer Piccolo Occluder device as well as ...

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf2/p020024b.pdf

Summary of Safety and Effectiveness Data - accessdata.fda.gov The. OPC formulated the following specific outcome measure criteria as guidelines for safety and efficacy of the AMPLATZER Duct Occluder: the Primary Efficacy.