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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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NeuRx DPS


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General
Study Status Completed
Application Number H100006 / PAS001
Date Current Protocol Accepted 09/28/2011
Study Name NeuRx DPS
General Study Protocol Parameters
Study Design Prospective Cohort Study
Data Source New Data Collection
Comparison Group No Control
Analysis Type Descriptive
Study Population Adult: >21
Detailed Study Protocol Parameters
Study Design Description This is a prospective, non-randomized, open-label, interventional study.
Study Population Description This study will enroll ALS patients who meet the HDE-approved device indications for use and undergo the surgical implantation procedure to receive the NeuRx DPS System after HDE approval. An important inclusion criterion is that patients must have chronic hypoventilation; an important exclusion criterion is that FVC < 45% predicted at time of surgery.
Sample Size Based on practical considerations in this small subpopulation of patients with ALS who meet the HDE indications for use, it is expected that 60 participants can be enrolled at 3 to 12 centers over three years. This sample size of 60 participants has 80% power to ensure that the major device-related adverse event rate at 9 months post implant does not exceed 40% (based on peak adverse event rate using same device for spinal cord injury indication [H070003]), assuming the true event rate is 23% (based on IDE), with 5% one-sided alpha. A sample size of 60 patients ensures that there will be at least 48 patients at risk at the beginning of the 6 to 9 months interval to analyze the AE rate at 9 months.
Data Collection This study will examine the following safety and probable benefit outcomes of interest:

Safety Outcome Measure: Occurrence of major device-related (including procedure-related) adverse events as defined as:

Serious capnothorax requiring invasive intervention (such as chest tube placement).

Mechanical ventilation for 24 hours or longer post-procedure.

Post-procedure extubation failure resulting in permanent tracheostomy ventilation (PTV).

Perioperative complication which delays the initiation of NeuRx DPS therapy.

Severe discomfort due to stimulation which is unable to be tolerated or resolved and results in interruption or discontinuation of NeuRx DPS therapy.

Device malfunction (e.g,. broken wire or stimulator) which interrupts or causes an undesired diminution of NeuRx DPS therapy (e.g., no stimulation in one hemi-diaphragm).

Electrode dislodgement from the diaphragm.

Wire infection.

Any other device- or procedure-related serious adverse event (SAE) that is fatal, life threatening, requires or prolongs hospitalization, or requires intervention to prevent permanent impairment or damage.

Probable Benefit Outcome Measure: Survival, defined as time to (a) death or (b) permanent tracheostomy mechanical ventilation (PTV) with discontinuation of pacing. (All deaths and PTV events will be reported regardless of relationship to the device or procedure.)

Follow-up Visits and Length of Follow-up 9 months

0 to 1 month, 1- 3 months, and every 3 months thereafter until post-implant follow-up completion

Interim or Final Data Summary
Actual Number of Patients Enrolled 60 (54 patients implanted)
Actual Number of Sites Enrolled 12
Patient Follow-up Rate Overall follow-up rate among those enrolled: 78% (47/60) The follow-up rate among those implanted was 87% (47/54).
Final Safety Findings The highest incidence rate of MDRAEs at 9 and 21 months was due to wire infection [21.7% (95%CI: 12.7, 35.8)], following by device malfunction which interrupts or causes an undesired diminution of NeuRx DPS therapy being [18.3% (95%CI: 9.9, 32.4)] at 9 months and [21.9% (95%CI: 12.2, 37.6)] at 21 months. Adverse events with less than 10% in both time points were, serious capnothorax requiring invasive intervention (such as chest tube placement), perioperative complication which delays the initiation of NeuroRX DPS Therapy, and any other device-or-procedure-related serious AE that is fatal, life threatening, requires or prolong hospitalization. At 9 months the rate for severe discomfort due to stimulation resulting in interruption or discontinuation of NeuRX DPS therapy was 0%, but reporting 4.2% (95%CI: 0.6, 26.1) at 21 months. The composite MDRAEs (patients with at least one MDRAE) was 42.7% (95%CI: 30.4, 57.6) at 9 months, and 47.9% (95%CI: 33.6, 64.7) at 21 months. Patients with severe discomfort due to stimulation resulting in interruption or discontinuation of NeuRx DPS therapy increased from 0% adverse events at 9 months and 4.2% events at 21 months, and device malfunction which interrupts or causes an undesired diminution of NeuRx DPS therapy with 18.3% at 9 months and 21.9% at 21 months. The rest of the incidence rates, were the same at 9 and 21 months. No cases were reported for the rest of the MDRAEs under study (i.e. mechanical ventilation for 24 hours or longer post- procedure, post-procedure extubation failure resulting in permanent tracheostomy ventilation (PTV), and electrode dislodgement from the diaphragm). The frequency (incidence) of major device-related AEs did not increased dramatically toward end of life because the incidence rates at 9 and 21 months slightly increased only for two MDREAs and the composite as explained above. Regarding the secondary objective, there was no significant relationship between survival time and the onset type (bulbar and limb), time from diagnosis to treatment, and use of NIV, riluzole or PEG in patients treated with the device.
Final Effect Findings No effectiveness study endpoints were included in the approved protocol.
Study Strengths & Weaknesses Strength: None

Weaknesses: Small sample size (60), 78.3% follow-up rate, and no concomitant control group was included.

Recommendations for Labeling Changes The PAS study design, methods and results must be included in the labeling. Additionally, it should be included the following Serious Adverse events:

3 cases of capnothoraces requiring invasive intervention with a chest tube; all resolved in 1-2 days.

1 case of history of poor pain control precluding the ability to program and use the DPS device.

1 case of pulmonary embolism perioperatively requiring hospitalization and having fatal resolution.

1 case of post-operative spasticity and development of bilateral lung infiltrates requiring 2 bronchoscopies, one with removal of a mucous plug.

Table 1: Incidence at 9 and 12 months for MDRAES in N-54 implanted patients (provided interactively on August 10, 2017).



NeuRx DPS Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
six month report 03/28/2012 03/28/2012 On Time
one year report 09/27/2012 09/27/2012 On Time
two year report 09/27/2013 09/27/2013 On Time
three year report 09/27/2014 09/26/2014 On Time
four year report 09/27/2015 09/25/2015 On Time
five year report 09/26/2016 10/03/2016 Overdue/Received
Final Report 12/26/2016 02/15/2017 Overdue/Received


Contact Us

Julie Unger
Project Manager, Post-Approval Studies Program
Food and Drug Administration
10903 New Hampshire Ave
WO66-4206v Silver Spring, MD
20993-0002

Phone: (301) 796-6134
Fax: (301) 847-8140
julie.unger@fda.hhs.gov

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