In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
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.
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.
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:
¿ 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.)
Followup Visits and Length of Followup
0 ¿ 1 month, 1- 3 months, and every 3 months thereafter until post-implant