Clinical Studies

Completed

Based on this study, consisting of 86 patients from 8 study centers, the U.S. FDA approved the NeuRx DPS^® under a Humanitarian Device Exemption (HDE) for use in people with ALS and symptoms of reduced breathing capability (chronic hypoventilation). The FDA reviewed the results of this clinical study and determined that the probable benefit to health from the use of the device outweighs the risk of injury or illness from its use in people who have ALS and reduced breathing capability and meet certain other criteria. This analysis of outcomes in the HDE study has been reviewed, audited and disseminated by the FDA in the Summary of Safety and Probable Benefit available on the FDA web site (http://www.accessdata.fda.gov/cdrh_docs/pdf10/H100006b.pdf).

Inclusion criteria:

• Age 18 or older
• Participants with familial or sporadic ALS diagnosed as laboratory-supported probable, probable, or definite according to the World Federation of Neurology El Escorial criteria will be eligible
• Forced Vital Capacity (FVC) between 50 – 85% of predicted values at time of screening
• FVC greater than 45% of predicted value at time of surgery
• Bilateral phrenic nerve function clinically acceptable as demonstrated by bilateral diaphragm movement with fluoroscopic sniff test or with EMG recordings and nerve conduction times
• No underlying cardiac or pulmonary diseases that would increase the risk of general anesthesia greater than the expected risk of the patient with ALS
• Negative pregnancy test in females of child-bearing potential

Results:

• IDE pivotal trial (N = 86, 8 study centers)
• The patients who used the NeuRx DPS^® plus non-invasive ventilation (NIV) survived 16 months longer (on average) than patients who just used NIV. This 16 month time frame is from the time of diagnosis. Survival time was measured until death or the need for a full time ventilator and a tube in the throat (tracheostomy).
• The patients who used the NeuRx DPS^® plus NIV survived 9 months longer (on average) than patients who just used NIV, when survival is measured from the initiation of NIV.
• Some patients had a feeding tube placed with the NeuRx DPS^®. All of these patients survived past 30 days.  Normally, 2 to 25 patients out of 100 (up to a fourth of all patients) would not survive this long.
• Some patients could not get used to or were unable to use NIV but used the NeuRx DPS^®. They survived an average of 16 months after getting the DPS.

Some patients had their sleep tested after using the NeuRx DPS^® for 4 months.  They tended to have better sleep than before they received DPS.

The study was stopped prematurely

The DiPALS study was an off-label, randomized-controlled trial intending to evaluate the NeuRx DPS® in patients with respiratory muscle weakness due to Motor Neuron Disease. This multi-center (6 sites in the UK) study was stopped prematurely due to safety concerns. The investigators compared 37 participants using Non-Invasive Ventilation (NIV) only to 37 participants using the NeuRx DPS® with NIV. The DiPALS results showed a median survival of 11 months post-implant of the group receiving the NeuRx DPS® vs 22 months for the NIV-only group. These results are strikingly different than those previously seen by U.S. investigators. The US IDE study and the on-label Post-Approval Study (PAS) reported post-implant median survival of 19.7 months and 21 months, respectively.

Based on this limited number of study participants, the U.K. study authors’ concluded that pacing causes harm. Yet the two leading ALS experts from the United States pointed out in a letter to the Editor of Lancet-Neurology that the investigator’s own data contradicts this statement. The UK study data indicates no association between survival and the use of pacing (HR 1:00 per additional hour use, 95% CI -0.92 to 1.09, p=0.92). Study participants tolerated stimulation well and only two discontinued use of pacing. The U.S. experts went on to state that the negative U.K. outcomes may have hinged on the fact that 30% of the participants in the NeuRx DPS® group did not use their NIV, as per the study’s protocol.  The U.S. ALS experts argued that the results actually support the conclusion that increased survival is correlated with the on-label use of NIV and NeuRx DPS® greater than 4 hours per day.

For additional study detail (www.controlled-trials.com/ISRCTN53817913)

RespiStimALS  (French Study)

The study was prematurely stopped

RespiStimALS is an off-label study, using a sham comparator, examining the early use of NeuRx® Diaphragm Pacing System (DPS) in ALS patients prior to the onset of chronic hypoventilation.  The study had fully enrolled 74 patients before it was prematurely discontinued.  The primary objective of the study was to demonstrate that intra-diaphragmatic phrenic stimulation delays the need for NIV in ALS.  The investigators secondary outcomes were overall survival from onset of symptoms and randomization, impact on quality of life, and adverse events.

All patients were implanted with a NeuRx DPS® then blindly randomized to an active (off-label use) or inactive device. Those with an inactive device had their device activated when their physician determined they had chronic hypoventilation (on-label).

As stated this was off-label use of the NeuRx DPS®. The FDA approved the use of the NeuRx DPS® in ALS patients with partially intact phrenic nerves and documented chronic hypoventilation. “We have always maintained, diaphragm pacing is for a select group of ALS patients that already have chronic hypoventilation but have intact lower motor neurons with loss of upper motor neuron control.” commented Dr. Raymond Onders Interim-Chair of Surgery & Remen Chair in Surgical Innovation at University Hospitals  of Cleveland and Professor of Surgery at Case Western Reserve University, “This study reaffirms this position and further supports our FDA approved indication; ALS patients with documented chronic hypoventilation and clinical confirmation of intact phrenic nerves.”

For more information: http://clinicaltrials.gov/show/NCT01583088