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Device System for Transcatheter Repair of Postinfarction Ventricular Septal Defect

Description:

  1. Device System for Transcatheter Repair of Postinfarction Ventricular Septal Defect

Fast-Track proposals will be accepted.

Number of anticipated awards: 1 Phase I, 1 Phase II

Budget (total costs, per award):  Phase I: up to $400,000 for 12-18 months; Phase II: up to $3,000,000 for up to 36 months

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.

Summary

Postinfarction ventricular septal defect (VSD) is an uncommon but devastating mechanical complication of acute myocardial infarction with extremely high mortality.  Patients already suffering myocardial dysfunction usually die from acute volume overload superimposed on cardiogenic shock.  Surgical repair confers an unacceptably high mortality, and the sole nitinol occluder device currently available under Humanitarian Device Exemption (St Jude Amplatzer Muscular VSD occluder) is highly unsatisfactory (too small, too rigid, too permeable, wrong geometry) and usually unsuccessful.

There is a clear need for a purpose-built device to achieve early occlusion of postinfarction VSD, which could be lifesaving in approximately 2-4000 patients annually.   This market size is too small for the large medical device manufacturers to address, but fortunately is suitable for Humanitarian Device Exemption regulatory pathway.

Project Goals

The goal of the project is to develop a device for percutaneous closure of postinfarction VSD in adults. First a prototype would be developed and tested in animals, and ultimately a clinical-grade device would undergo regulatory development for clinical testing, which NIH DIR offers to assist in performing.

Offerors are encouraged to include concrete milestones in their proposals, along with detailed research and development plans, risk analysis, and contingency plans, both for Phase I and Phase II.

Offerors are advised to plan travel to NHLBI in Bethesda Maryland, and are expected to plan meeting at project initiation, mid-project to determine what iteration is necessary, and at project completion.

Phase I Activities and Expected Deliverables

A phase I award would develop and test a postinfarction VSD occluder prototype.  The NHLBI Division of Intramural Research laboratory may be willing to test the final prototype in vivo, at no expense to the offeror.  The offeror is expected independently to perform animal testing as needed to meet phase I requirements. 

Device requirements include:

  1. Delivery profile of 12-14 Fr or smaller
  2. Suitable for antegrade (transvenous) or retrograde (transarterial) transcatheter delivery
  3. Designs must address a range of defect diameters from 20-40mm.  Because these defects are variable and non-uniform, designs are invited that specifically address this heterogeneity, including with non-circular profiles.
  4. Designs are invited that are able to accommodate a range of ventricular septal wall  thicknesses
  5. Designs are invited to accommodate specific anatomic variations, including postinfarction VSDs at or near the ventricular apex and bordering on the anterior or posterior free wall
  6. Designs are invited that are self-centering so that the central portion of the device fills the entire space created by the VSD
  7. Devices must be completely repositionable and recapturable without exacerbating myocardial injury
  8. Devices must contain a central guidewire port to allow position to be maintained despite retrieval or repositioning
  9. Designs are invited that have small, little or no right ventricular disc to avoid interference from right ventricular trabeculation
  10. Designs that balance the forces required to assure permanent fixation without tearing necrotic margins, even if retrieved or repositioned
  11. Devices must achieve nearly complete hemostasis (obliteration of shunt flow) within two hours or fewer, although immediate hemostasis is preferred.  Most designs will require low-profile hemostatic material within the “left ventricular” and “septal neck” elements of the device.  Because of the risk of hemolysis the designs that impose a “barrier” are preferred over permeable “meshes.”
  12. Implants must be MRI compatible so that cardiac function and flow can be measured unimpeded after implantation using MRI, and MRI conspicuity is desirable
  13. Designs having absorbable components are welcomed
  14. The implant should have mechanisms or a range of morphologies to avoid heart valve entrapment or distortion
  15. Proposals should include specific plans, and device features, to allow operator recovery of the device if it embolizes after release
  16. The delivery system and implant must be conspicuous under the proposed image-guidance modality whether ultrasound or X-ray, and must be conspicuous under X-ray after release.  The delivery system must be kink-resistant under the intended use conditions.
  17. The device should accomplish acute or subacute occlusion without early or late thromboembolism, and proposals should specifically address these considerations
  18. The system should be accompanied by a proposed robust methodology or device to select the appropriate device size
  19. The results of a pre-IDE meeting with FDA CDRH, which indicates a sufficiently mature device and which will guide Phase II.

Final payment is contingent on meeting all of the above requirements.

Phase II Activities and Expected Deliverables

In addition to meeting all requirements specified for Phase I, the phase II award would allow mechanical and safety testing and regulatory development for the device to be used in human investigation.  The NHLBI Division of Intramural Research laboratory offers but does not require to perform an IDE clinical trial at no cost to the awardee.  Complete Investigational Device Exemption documentation and license and a suitable supply of clinical materials would constitute the final deliverable.  The offeror will provide a complete report of prior investigation along with all other elements of the IDE application and accompanying regulatory correspondence.  For all purposes, a Humanitarian Device exemption or an expedited Premarket Approval would be considered responsive in place of IDE.

The offeror should provide clear project milestones that trigger review and payment, along with detailed research and development plans, risk analysis, and contingency plans.  Representative project milestones include, not necessarily sequentially:

  1. a device build and short-term survival study to identify additional failure modes
  2. elements of a quality system including product specification, design and failure mode analysis, design verification and validation and test plan, biocompatibility and sterility assessment and plan, design review, design freeze, design transfer to manufacturing
  3. manufacturing plan
  4. iterative ex vivo testing such as animal explants
  5. iteration for unexpected design or device failure
  6. FDA pre-IDE meeting #1 and #2
  7. modeling and fatigue study for chronic implant
  8. chronic GLP animal studies
  9. design of clinical protocol including informed consent, risk analysis for early feasibility, and case report form, whether or not conducted in collaboration with NHLBI Division of Intramural Research laboratory
  10. preparation of IDE
  11. submission and resubmission of IDE
  12. manufacturing of test articles.

The offeror is expected to conduct animal experiments and provide care as required to obtain the IDE.  The offeror is advised to propose how to proceed in case of hold from FDA.

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) conducts and supports research to expand and disseminate fundamental knowledge about the effects of alcohol on health and well-being, and apply that knowledge to improve diagnosis, prevention, and treatment of alcohol-related problems, including alcohol use disorder, across the lifespan. To learn more about the NIAAA, please visit our web page at https://www.niaaa.nih.gov.

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