Carag AG received investigational device exemption (IDE) approval from the U.S. FDA for its Carag Bioresorbable Septal Occluder (CBSO). The device is the first transcatheter septal occluder with a nonmetal, bioresorbable framework. The Baar, Switzerland-based company plans a "swift start" for a staged study trial in the U.S. with 250 patients, Carag's CEO Jérôme Bernhard told BioWorld.
The device treats atrial septal defects (ASD) or holes in the wall that separate the left and right atria of the heart. Congenital ASDs occur in about 6 in 10,000 births. While larger ASDs require surgery in infancy, many smaller ones remain undetected for years.
In addition, transseptal puncture, a procedure used to diagnose and identify patients for cardiac valve surgery, creates an iatrogenic ASD, which also may require closure, depending on its size.
Both types of ASD allow blood to return from the left to the right side of the heart, which can lead to enlargement of the right ventricle. Adults with ASD may experience shortness of breath, fatigue, edema, heart arrhythmias, stroke or heart murmur.
Transcatheter implants generally close the hole by using a metal framework that clamps it shut. Leaving the metal framework behind, however, can pose some long-term issues, including perforation, erosion, arrhythmia and thrombus formation. The metal also changes the electrical and mechanical properties of the septum.
“The long-term presence of metal in the heart is obviously not desirable for any patient, particularly when the framework is no longer needed once the septum has healed. Furthermore, with the number of heart procedures requiring septal crossing growing fast, one of the key unmet needs is to keep all future treatment options open,” Bernhard said.
An aging population has driven greater demand for new procedures to treat left-sided cardiac disorders, such as left atrial appendage occlusion, mitral valve disease and heart failure.
“These procedures require a septum that can be crossed at specific locations, without being hindered by a metallic obstruction,” Bernhard explained.
Unlike other transcatheter implants, the CBSO’s poly-lactic-co-glycolic acid framework is fully resorbed within 24 months. The device is covered by tissue in three months.
“The possibility of using resorbable devices that close the hole in the atrial septum, then disappear leaving no foreign body in the heart, may represent one of the major advances in transcatheter interventions,” said Mario Carminati, director of the Pediatric and Adult Congenital Cardiology Center at IRCCS Policlinico San Donato University Hospital in Milan.
The upcoming trial will be the largest undertaken by Carag to date. Sites will include major pediatric and structural heart centers, including the Joe DiMaggio Children's Hospital in Florida and Los Robles Medical Center in California, where the study’s co-principal investigators, Larry Latson and Saibal Kar, are based.
“We are conducting the preparatory works for a swift start of the trial soon, while monitoring the pandemic situation; we will communicate more details as soon as possible,” Bernhard said. The company hopes to begin trial enrollment in late 2020.
Carag’s first-in-human trial found the device had excellent closure results both at the time of the procedure and two years later. No serious device-related complications were reported.
The device comes in three sizes. The largest has a diameter of 33 mm and is capable of closing a hole of 25 mm. It can be retrieved and redeployed at all stages of delivery and can be repositioned even after deployment. Platinum-iridium markers enable visualization using X-ray or echo technology.
Carag received the CE mark for the CBSO in 2017 for both ASD and patent foramen ovale, another type of congenital defect in which a flap-like opening between the right and left atria that typically closes during infancy remains open.
So far, the CBSO has been made available in a controlled market release to selected centers in Germany and Switzerland. A multicenter, international, postmarket registry is monitoring the device’s clinical performance and safety.
The U.S. IDE is only for atrial septal defect.
“We are currently focused on [the] ASD application in the U.S. Our technology has equally great benefits for PFO patients,” Bernhard said. “We are evaluating all options to continue making our technology available to as many patients as possible.”