Amplatzer Piccolo Occluder clinical trial for percutaneous closure of the patent ductus arteriosus in patients ≥700 grams

Abstract

Objectives: Characterize the safety and effectiveness of the Amplatzer Piccolo Occluder for patent ductus arteriosus (PDA) closure.

Background: The presence of a hemodynamically significant PDA has been associated with an increased risk of morbidity and mortality in children born premature.

Methods: This was a single arm, prospective, multicenter, non-randomized study to evaluate the Amplatzer Piccolo Occluder to treat PDA in patients ≥700 g. From June 2017 to February 2019, 200 patients were enrolled at nine centers, with 100 patients weighing ≤2 kg. Primary effectiveness endpoint was the rate of PDA closure at 6-month follow-up. Primary safety endpoint was the rate of major complications through 6 months. Secondary endpoint was rate of significant pulmonary or aortic obstruction through 6 months' follow-up.

Results: The implant success rate was 95.5% (191/200) overall and 99% in patients ≤2 kg (99/100). The primary effectiveness endpoint was achieved in 99.4% of implanted patients. Four patients experienced a primary safety endpoint event (2 transfusions, 1 hemolysis, and 1 aortic obstruction). There were no branch pulmonary artery obstructions. Five patients, all ≤2 kg, were noted to have worsening of tricuspid regurgitation (TR) after the procedure. None of the TR incidences manifested clinically. The Amplatzer Piccolo Occluder received FDA approval in January 2019 and became the first device approved for PDA closure in patients ≥700 g.

Conclusions: This study supports the safety and effectiveness of the Amplatzer Piccolo Occluder, particularly in patients between 700 g and 2 kg where there is currently a significant unmet need in the United States. ClinicalTrials.gov identifier: NCT03055858.

Keywords: ADO II AS; Amplatzer Piccolo Occluder; FDA; patent ductus arteriosus; prematurity; transcatheter closure.

FIGURE 1

High‐resolution photographs of the 4 mm Amplatzer Piccolo Occluder of three different lengths [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

PDA Assessment prior to closure in an 800 g, 21‐day‐old, ex‐24‐week gestational age infant using echocardiographic and radiologic landmarks. (a) Angiogram obtained in the PDA in a left anterior oblique projection and caudal projection prior to device closure demonstrates the PA bifurcation clearly. The PDA is completely to the left of the esophageal temperature probe. (b) Angiogram obtained in the PDA in straight lateral projection, demonstrates a large fetal type (Type‐F) PDA. The temperature probe in the esophagus marks the aortic end of the PDA and the tip of a peripherally inserted central catheter (PICC) in the superior vena cava (SVC) marks the pulmonary end of the PDA. The PDA is typically measured in this projection. (c) TTE of a large fetal type (Type‐F) PDA in a parasternal short axis view. The measurements are best made in this projection. The length is typically made in a curvilinear fashion as the PDA is hockey stick shaped. (d) Color Doppler interrogation in the parasternal short axis view prior to device closure demonstrates continuous left to right shunt across the PDA [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

PDA occlusion using the 4‐2 Amplatzer Piccolo Occluder in an 800 g, 21 days old, ex‐24‐week gestational age infant (same patient in FIGURE 2). (a) Angiogram obtained via the TorqVue LP catheter prior to releasing the device in left anterior oblique projection and caudal projection, demonstrates no LPA stenosis. The device is entirely to the left of the esophageal temperature probe. (b) Angiogram obtained via the TorqVue LP catheter prior to releasing of the device in straight lateral projection, demonstrates no LPA stenosis. The device is entirely intra‐ductal and is positioned between the esophageal temperature probe and the PICC in the SVC. The device is splayed out along the long axis (superior edge) of the PDA and splayed together along the short axis (inferior edge) of the PDA—making a “Pac‐Man” configuration. The orientation of the device along the long axis of the PDA (10 o' clock position) is a good indication of proper device position. (c) 2D view from the suprasternal notch immediately after device implantation within the PDA demonstrates a completely intra‐ductal location of the device with no stenosis of the LPA or the aorta. (d) Color Doppler interrogation from the suprasternal notch immediately after device implantation within the PDA confirms no residual shunt and no stenosis of the LPA or the aorta [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Histograms. (a) Histogram of patient weights of the 200 patients enrolled in the U.S. IDE and the CAP studies. (b) Histogram of weight distributions for patients ≤2 kg (N = 100). (c) Histogram of gestational age at birth for patients ≤2 kg (N = 100) [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

PDA morphology. (a) Illustration of the six morphologic types of PDA used for classification in the US IDE and the CAP studies. (b) PDA morphology for patients ≤2 kg (N = 100) dominated by the fetal type (Type‐F) morphology. (c) PDA morphology for patients >2 kg (N = 100) dominated by the conical type (Type‐A) morphology [Color figure can be viewed at wileyonlinelibrary.com]