100 MRI Myocardial Needle Chemoablation Catheter
Fast-Track proposals will be accepted.
Direct-to-Phase II proposals will be accepted.
Number of anticipated awards: 1
Budget (total costs):
Phase I: up to $300,000 for up to 18 months
Phase II: up to $2,000,000 for up to 24 months
PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.
Myocardial catheter ablation is commonly performed for the treatment of rhythm disorders, using radiofrequency energy, typically guided using X-ray and/or electromagnetic positioning. Available non-surgical technologies do not allow clear depiction of myocardium being ablated. MRI-guided needle catheter chemo-ablation, for example using focal injection of caustic agents such as acetic acid doped with MRI contrast agents, may allow targeted disruption of small segments of myocardium in the treatment of rhythm disorders such as ventricular tachycardia and in the treatment of structural heart disease such as hypertrophic cardiomyopathy. Preclinical feasibility of at least two different MRI injection needle catheter systems has been demonstrated and published for the application of direct endomyocardial cell injection, including by our labs. No commercial options are available.
An MRI myocardial needle injection catheter system may enable a new family of non-surgical cardiovascular treatments for rhythm and structural heart disease.
The goal of the project is to develop an endomyocardial injection needle chemoablation catheter that is safe for operation during MRI, to allow targeted myocardial delivery of caustic agents. First a prototype would be developed and tested in animals, and ultimately a clinical-grade device would undergo regulatory development for clinical testing. NIH offers to perform clinical testing at no charge to the contractor.
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.
Proposals must include a detailed description of the regulatory strategy, including plans for a pre-submission meeting with the US Food and Drug Administration (FDA) in Phase I. Offerors must include key personnel on the project with appropriate and relevant regulatory experience.
Offerors are advised to plan travel to NHLBI in Bethesda, Maryland, and are expected to plan meetings 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 support the development and testing of a myocardial injection needle prototype. The contracting DIR lab is willing to provide feedback about design at all stages of development. The contracting DIR lab will test the final deliverable device for success in vivo in swine.
Specific Phase I deliverables include:
• 9Fr or smaller.
• Suitable for use via femoral artery retrograde across aortic valve and via jugular and femoral venous access to the right sided cardiac chambers.
• A needle that can be delivered to multiple endomyocardial targets, achieve stable positioning, and that can penetrate the myocardium without causing significant harm while delivering injectate. Solutions should allow a user-selected injection depth and may be spring-loaded or offer alternative penetration capabilities.
• Sufficient radius of curvature to access all parts of left ventricle endocardial surface including left ventricle outflow tract, and all parts of right ventricle including septum and outflow tract. Suitable solutions incorporate deflectable catheters with extensible needle elements; alternative embodiments may use multiple coaxial curved catheters that can be torqued, or other approaches.
• Visibility during MRI: (1) “Active” design incorporating MRI receiver coils for mandatory shaft and tip and needle visibility during MRI; (2) Receiver coils should be conspicuous under MRI using “profiling” or “tracking” techniques as described in publications from the contracting NHLBI DIR laboratory (See Saikus CE and Lederman RJ, JACC Cardiovascular Imaging, 2009, http://www.pubmed.gov/19909937); (3) The “active” receiver coils must operate for testing on a Siemens Aera 1.5T MRI scanner installed at contracting NHLBI DIR laboratory.
• There should be a distinct imaging signature to confirm needle deployment. One suitable option is a separate receiver channel for the needle.
• Simultaneous ability to record intracardiac electrograms from the needle site, either bipolar or unipolar, including safe electrode transmission lines.
• Free from clinically-important heating (2oC at 1W/kg SAR) during continuous MRI at 1.5T.
• Proposals for alternative visualization and heat-mitigation strategies, such as “active” or “inductively-coupled” receiver coils, are encouraged, but must operate for testing on a Siemens Aera 1.5T MRI scanner installed at the contracting NHLBI DIR laboratory.
• A comprehensive report of test results, including in vivo test results if not performed at NHLBI.
• Sufficient devices to test the final device in vivo at the contracting NHLBI DIR laboratory.
• A detailed report of pre-submission interactions with the FDA Center for Devices and Radiological Health (CDRH) identifying requirements for Investigational Device Exemption (IDE) development under Phase II, including meeting minutes, if available.
Consideration for transition to Phase II funding will include regulatory progress toward US market access. Consideration may include the status of the contractor’s interactions with the FDA. NHLBI encourages contractors to consider requesting designation to the FDA’s Expedited Access for PMA Devices (EAP) program (http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM393978.pdf) during the Phase I award period.
Phase II Activities and Expected Deliverables
A Phase II award would allow mechanical and safety testing and regulatory development for the device to be used in human investigation, whether under Investigational Device Exemption (IDE) or under 510(k) marketing clearance.
Activities in Phase II should align with the required testing and development milestones agreed upon with the FDA in Phase I. The contracting DIR lab offers to perform an IDE clinical trial at no cost to the awardee.
IDE license or 510(k) clearance, along with twenty clinical investigational prototypes, would constitute the deliverable.
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:
• a device build and short-term survival study to identify additional failure modes.
• elements of a quality system including product specification, design and failure mode analysis, design verification and test plan, biocompatibility and sterility assessment and plan, design review, design freeze.
• manufacturing plan.
• iterative ex vivo testing such as animal explants.
• iteration for unexpected design or device failure.
• pre-submission meetings with FDA.
• chronic or acute GLP animal studies as required.
• 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.
• preparation of IDE.
• submission and resubmission of IDE.
• manufacturing of test articles.
Specific Phase II deliverables include:
• All characteristics of Phase I deliverable, and in addition:
• Catheter outer diameter reduced to 8Fr or smaller for phase II.
• A complete report of prior investigation along with all other elements of the IDE application and accompanying regulatory correspondence.
• Suitability of the injection system for delivery of viable cells, while outside the scope of this contract, is encouraged.