SBIR-STTR Award

Primary and secondary tricuspid valve regurgitation can cause disabling right heart failure, hepatic dysfunction, cardiorenal syndrome, and death. Primary surgical repair or replacement is highly morbid, especially at the advanced stage of typical clinical presentation. Transcatheter repair using marketed and investigational clip-type devices is poorly suited for the trileaflet tricuspid valve. There is substantial unmet need. The goal of this project is to develop a catheter system to achieve a non-surgical off-pump tricuspid valve leaflet repair that allows three or more sutures to reappose three or more tricuspid valve leaflets to repair secondary or primary tricuspid valve regurgitation, sometimes described as “clover-leaf repair.” Under Phase I, the contractor will develop and test a functioning prototype system.

Transmural Systems LLC has developed a purpose-built Transcatheter Cavopulmonary Bypass Endograft (TCBE) that will allow for interventional cardiologists to treat children born with functional single ventricle (FSV), a form of cyanotic congenital heart disease. Children born with FSV represent 7.7% of all patients withcongenital heart defects (CHD). In the United States, about 2000 children are born with FSV each year. FSV isan umbrella term applied to several complex CHDs, which includes Hypoplastic Left Heart Syndrome (HLHS),Pulmonary Atresia with Intact Ventricular Septum, Tricuspid Atresia, and Unbalanced Atrioventricular Canal,among others. Without treatment, the actuarial survival rates of patients with FSV are only 53% at one yearand 42% at ten years of age. The development of palliative surgical procedures, however, has markedlyimproved the survival of patients with FSV, but these surgeries and subsequent lengthy stays in thecardiovascular intensive care unit contribute significantly to mortality and morbidity of FSV patients. A lessinvasive clinical alternative has not to date been available for these surgical procedures. A transcatheteralternative would offer the possibility of reduced mortality and morbidity, as well as reduced hospital stays andrelated costs. Thus, there is an urgent clinical need for an effective percutaneous approach to treating FSV. Ina previous Phase II contract, Transmural Systems engineered the TCBE, intended to create a Bi-directionalGlenn shunt between the Superior Vena Cava and Right Pulmonary Artery. The TCBE design has beenoptimized and extensively tested in vascular bench models and in acute and chronic Good LaboratoryPractices (GLP) swine experiments. The TCBE has performed with excellent efficiency and safety in theseexperiments. The goal for this Phase IIB project is to utilize Transmural's TCBE in a clinical trial to test thesafety and therapeutic value in treating FSV patients. An early feasibility study (EFS) will be the focus of thisPhase IIB Award. Transmural Systems will be significantly guided by the expertise of Dr. Robert J. Ledermanof the NHLBI, Dr. Kanishka Ratnayaka of the NHLBI and Rady Children's Hospital, Dr. John Moore, Dr. JohnNigro, and Dr. Howaida El-Said, all of Rady Children's Hospital, who will assist in running and conductingclinical studies. The goal of EFS completion will be achieved through the execution of the following SpecificAims: 1) manufacture and sterilize a batch of TCBE devices utilizing Good Manufacturing Practices (GMP) forpreclinical testing and to support EFS; 2) execute preclinical testing to demonstrate the TCBE designspecifications meet the design requirements, generate a report to submit to Food and Drug Administration(FDA) as part of an Investigational Device Exemption (IDE) package, and receive approval to start the EFS;and 3) complete enrollment of EFS (up to n=10 subjects). These proposed Specific Aims are vital steps incommercializing the TCBE (through a future Humanitarian Device Exemption trial) that will be the only deviceon the market purposefully created for FSV.

Public Health Relevance Statement:
PROJECT NARRATIVE Transmural Systems' Transcatheter Cavopulmonary Bypass Endograft (TCBE) is a purpose-built transcatheter medical device design and intended to treat patients with Functional Single Ventricle (FSV), a form of cyanotic congenital heart disease (CCHC). The TCBE device can address a significant gap in treatment options for children with FSV; as a transcatheter alternative to open heart surgery, it will offer the possibility of reduced mortality and morbidity, as well as reduced hospital stays and related costs. By completing the Specific Aims and executing the Commercialization Plan outlined in this proposal, Transmural Systems will provide a transcatheter solution to the under-serviced patient population of children born with FSV.

Project Terms:
<0-11 years old>

<10 year old><10 years of age>