Notice Number: NOT- HL-08-122
Key Dates
Release Date: June 30, 2008
Response Date: August 22, 2008
Issued by
National Heart, Lung, and Blood Institute (NHLBI) (http://www.nhlbi.nih.gov)
Purpose
This Notice is a time-sensitive Request for Information (RFI) regarding a potential clinical trial of ventricular assist devices (VADs) in NYHA advanced Class III/Early Class IV heart failure patients. This information will be used to assess the interest of the mechanical circulatory support device industry to support a collaborative trial.
This RFI is for planning purposes only and should not be construed as a solicitation for applications or proposals and/or as an obligation in any way on the part of the United States (U.S.) Federal government. The Federal government will not pay for the preparation of any information submitted and/or for the government's use of that information. Information that is provided by a respondent that is confidential commercial or financial information will be maintained in confidence and will not be publicly disclosed unless required by FOIA as determined by the NIH FOIA Office or a court of competent jurisdiction.
Background
The National Heart, Lung, and Blood Institute (NHLBI) convened a working group of experts on heart failure cardiology, cardiac surgery, clinical trial design, medical ethics, and regulatory affairs on March 27-28, 2008, in Crystal City, Virginia, to advise the NHLBI on research directions for the treatment of advanced heart failure through clinical trials using ventricular assist devices (VADs). The executive summary of the working group can be found at http://www.nhlbi.nih.gov/meetings/cu-vad.htm.
The working group considered the highest priority to be a clinical trial to assess the use of VAD therapy in patients who are less ill than those currently eligible for destination therapy.
While many trial details are to be determined, the working group made a number of specific recommendations. These are provided below.
Patient Population Recommendations
- Patients should be ill enough to potentially experience both functional and survival benefits from the therapy without undue risk.
- The estimated mortality rate for this group should be no less than 30% at one year.
- Inclusion criteria include:
- hospitalization in past 6 months
- New York Heart Association (NYHA) Class IV or Advanced Class III*
- maximal evidence-based therapies for 3 months
- duration of heart failure of at least a year
- no inotropic support for 30 days prior to enrollment
Trial Design Recommendations
- Randomized control trial design with VAD and optimal medical management (OMM) arms
- 1:1 randomization ratio between OMM and VAD therapy.
- Initial pilot phase followed by a larger definitive phase.
- Initial phase to assess feasibility of enrollment and refine the target population, endpoints, and definitions.
- Pilot phase patients could be rolled over into the definitive phase of the trial.
- Criteria for moving to the definitive phase might include good enrollment, low complication rates, and estimation of an event rate sufficient to complete the trial.
- Initial estimate of the number of patients needed to adequately power such a trial is 250-300.
- A composite primary endpoint of survival and functional status was recommended where the improvement in functional status would need to be substantial and assessed through objective metrics.
- Survival would need to be at least as good as that in the control group.
- Secondary endpoints would be hospitalizations, complications, and quality-of-life metrics.
- VADs would need to be qualified for the trial based on well-defined requirements.
- If two devices or more are qualified and included in the trial, a patient randomized to the device arm of the trial would receive a device available at that particular site in order to capitalize on surgical experience with specific devices.
- Investigators could pre-specify which device or devices are to be used at their center and sites would be chosen to ensure equal use of qualified devices.
- Conduct the trial at leading centers by surgeons who have performed a least 12 implants of the VAD(s) to be used at the specific center for the trial.
The importance of testing a strategy of therapy rather than a specific device was emphasized, noting that the field of mechanical circulatory support would best be served by including multiple devices, if feasible. Additionally, the working group recognized that a large majority of the funding for the trial should be provided by industry.
With these recommendations in mind, the NHLBI desires input from the mechanical circulatory support industry to gauge their enthusiasm and interest in collaborating and supporting this potential trial. Responses to this RFI will be used for this purpose.
Information Requested
This RFI invites industry experts and representatives from mechanical circulatory support companies to provide responses to the following questions:
- What are essential characteristics of any VAD to be included in the trial?
- Is your company willing to have one or more of the VADs it produces included in this trial? If so, which ones? If not, please provide reasons and identify issues that, if resolved, would make your company willing to participate.
- Please describe the regulatory status for each VAD that your company might wish to include in the trial. If not currently approved for use in the U.S., please provide information on its current status (such as completed in vitro and in vivo studies, estimates of the number of implants to date, approvals outside of the U.S., Investigational Device Exemption status) and when you anticipate that it might be available and ready for use in the trial.
- What material, financial, and/or in-kind resources would you be willing to provide if your company were to participate in the trial? If possible, please specify the level and/or amount of support which your company would be willing to provide.
- What are essential characteristics of the trial design necessary for your participation in a collaborative VAD trial?
- Would your company be willing and able to comply with the NHLBI policy on third party involvement in clinical trials? The policy provides specifics on data control and ownership and can be accessed at http://www.nhlbi.nih.gov/funding/policies/thirdparty.htm.
Responses
Please submit your responses to VAD-Industry-RFI@nhlbi.nih.gov by August 22, 2008.
Inquiries
Questions about this request for information may be directed to:
J. Timothy Baldwin, Ph.D.
Program Director
Advanced Technologies & Surgery Branch
Division of Cardiovascular Diseases
National Heart, Lung, and Blood Institute
Two Rockledge Centre, Room 8206
6701 Rockledge Drive
Bethesda, MD 20892-7940
Phone: (301) 435-0513
Fax: (301) 480-1454
E-mail: baldwint@nhlbi.nih.gov
and Human Services (HHS)
