Electrical Activation of The Diaphragm for Ventilatory Assist

• Sponsor: Synapse Biomedical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00010374
• Collaborator: University Hospitals Cleveland Medical Center (Other), Shepherd Center, Atlanta GA (Other)
• Enrollment: 54
• Locations: 5
• Arm: 1
• Duration (Months): 104
• Patients Per Site: 10.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

OBJECTIVES:

The objectives of this study are to test the Diaphragm Pacing Stimulation (DPS) System for treating chronic ventilatory insufficiency in persons with respiratory muscle paralysis. The hypothesis being tested in the clinical trial is that laparoscopic stimulation of the diaphragm at the motor point with intramuscular electrodes is safe and effective in providing significant ventilatory support to individuals who are otherwise dependant on a mechanical ventilator. Patients in our initial study group have all suffered from high-level spinal cord injury and were full-time dependant on positive pressure mechanical ventilation prior to inclusion.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injury; Quadriplegia	Device: NeuRx DPS	N/A

Detailed Description

System: NeuRx RA/4 Diaphragm Pacing Stimulation System

Summary:

The NeuRx-RA/4 is intended to be used by individuals that have sustained a spinal cord injury, requiring aid with respiration. The device connects to the diaphragm which delivers current to stimulate muscle contractions to aid in respirations.

This device currently holds an Investigational Device Exemption No. G920162 in the United States and is currently undergoing clinical trials at University Hospitals (Cleveland), Shepherd Center (Atlanta) and Vancouver (Canada).

Introduction:

The purpose of the study is to determine if a new, investigational diaphragm pacing system can provide part or full time respiratory support to spinal cord injured persons who normally need a mechanical ventilator. Patients with high-level spinal cord injuries typically experience chronic ventilatory insufficiency due to respiratory muscle paralysis; these patients must be supported predominantly through positive pressure mechanical ventilation with a ventilator.

The diaphragm pacing system (NeuRx-RA/4) provides an electrical signal to the motor point of the muscle that causes the diaphragm to contract and allows patients to breathe more naturally.

Synapse Biomedical, in conjunction with Case Western Reserve University and University Hospitals of Cleveland, are evaluating activating the diaphragm with percutaneous intramuscular electrodes implanted laparoscopically. This eliminates any direct contact with the phrenic nerve, allows all circuitry and electronics to remain outside the body, and provides direct, selective activation to each hemidiaphragm.

The NeuRx RA/4 Diaphragm Pacing Stimulation (DPS) System has been implanted in 49 individuals with high-level spinal cord injury, resulting in over 20 years of cumulative active implantation time. The longest term patient was implanted March 6, 2000 and has been using the DPS System as his sole means of respiratory support for over five years. With the exception of the second patient, who does not meet our revised inclusion criteria and has gained no benefit from the implant, all of the remaining patients have been able to achieve significant tidal volumes with the DPS System. Based on the current results, the NeuRx RA/4 DPS System has demonstrated safety and efficacy in patients with high-level spinal cord injury.

Given the results to date the study has demonstrated preliminary efficacy in this patient population. With no unexpected significant adverse events reported the NeuRx RA/4 DPS System has performed reliably and safely in this patient population.

Device Description: The NeuRx RA/4 Respiratory System is manufactured by Synapse Biomedical. The NeuRx RA/4 System comprises the following components: an external, battery powered Stimulator Device, an associated Programmer/Controller, Intramuscular Electrodes, associated percutaneous Lead Wires, a Surgical Placement Tool Set, and a surgical Mapping Station.

Inclusion Criteria:

• Age 18 years or older

• Cervical spinal cord injury dependent on mechanical ventilation

• Clinically stable following acute spinal cord injury

• Bilateral phrenic nerve function clinically acceptable as demonstrated with EMG recordings and nerve conduction times

• Diaphragm movement with stimulation visible under fluoroscopy

• Clinically acceptable oxygenation on room air (>90%)

• Hemodynamically stable

• No medical co-morbidities that would interfere with the proper placement or function of the device

• Committed primary caregiver

• Negative pregnancy test in females of child-bearing potential

• Informed consent from patient or designated representative

Exclusion Criteria:

• Co-morbid medical conditions that preclude surgery

• Active lung disease (obstructive, restrictive or membrane diseases)

• Active cardiovascular disease

• Active brain disease

• Hemodynamic instability or low oxygen levels on room air

• Hospitalization for or a treated active infection within the last 3 months

• Significant scoliosis or chest deformity

• Marked obesity

• Anticipated poor compliance with protocol by either patient or primary caregiver.

• Currently breastfeeding

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multi-Center Pivotal Study of NeuRx RA/4 Ventilatory Assist Device
• Study Start Date: Feb 1, 2000
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NeuRx DPS Laparoscopic implantation of 4 NeuRx DPS electrodes and subsequent pacing using the DPS system.	Device: NeuRx DPS; Laparoscopic implantation of diaphragm electrodes and subsequent pacing with the NeuRx DPS.

Outcome Measures

Primary Outcome Measures

1. Enrolled Subjects Achieve Clinically Acceptable Tidal Volume Sustained Over a Continuous 4 Hour Period. [Within one year after implantation]

   Number of enrolled subjects that successfully maintained clinically acceptable tidal volumes greater than basal requirements over a continuous 4 hour period.

Secondary Outcome Measures

1. Achieve Clinically Acceptable Basal Metabolic Requirement of Tidal Volume Measured in ml During Chronic Stimulation. [Within one year after implantation]

   To evaluate the ability of NeuRx DPS therapy to replace mechanical ventilation for patients on a chronic use basis, a secondary indicator of this objective is tidal volume (Vt) measured in ml during chronic stimulation.

2. Number of Patients That Use NeuRx DPS to Breathe Without the Assistance of a Mechanical Ventilator for 24 Continuous Hours a Day [Within one year of implantation]

   Number of patients that can achieve at least 24 hours daily use of the NeuRx DPS without the assistance of a mechanical ventilator.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 years or older

• Cervical spinal cord injury dependent on mechanical ventilation

• Clinically stable following acute spinal cord injury

• Bilateral phrenic nerve function clinically acceptable as demonstrated with EMG recordings and nerve conduction times

• Diaphragm movement with stimulation visible under fluoroscopy

• Clinically acceptable oxygenation on room air (>90%)

• Hemodynamically stable

• No medical co-morbidities that would interfere with the proper placement or function of the device

• Committed primary caregiver

• Negative pregnancy test in females of child-bearing potential

• Informed consent from patient or designated representative

Exclusion Criteria:

• Co-morbid medical conditions that preclude surgery

• Active lung disease (obstructive, restrictive or membrane diseases)

• Active cardiovascular disease

• Active brain disease

• Hemodynamic instability or low oxygen levels on room air

• Hospitalization for or a treated active infection within the last 3 months

• Significant scoliosis or chest deformity

• Marked obesity

• Anticipated poor compliance with protocol by either patient or primary caregiver

• Currently breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Craig Hospital	Englewood	Colorado	United States	80113-2811
2	Shepherd Center	Atlanta	Georgia	United States	30309-1465
3	University Hospital Of Cleveland	Cleveland	Ohio	United States	44106
4	The Methodist Hospital	Houston	Texas	United States	77030
5	Vancouver CoastHealth	Vancouver	British Columbia	Canada	V5Z 1M9

Sponsors and Collaborators

• Synapse Biomedical
• University Hospitals Cleveland Medical Center
• Shepherd Center, Atlanta GA

Investigators

• Principal Investigator: Raymond Onders, MD, University Hospitals Cleveland Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Synapse Biomedical
• ClinicalTrials.gov Identifier: NCT00010374
• Other Study ID Numbers: CLIN 20-0000-0009
• First Posted: Feb 2, 2001
• Last Update Posted: Aug 18, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Synapse Biomedical: Diaphragm for Ventilatory Assist; environmental/toxic disorders; neurologic and psychiatric disorders; rare disease; spinal cord injury
• Additional relevant MeSH terms: Spinal Cord Injuries; Quadriplegia

Study Results

Participant Flow

Recruitment Details	This study enrolled patients who have suffered from high-level spinal cord injury, are full-time dependent on positive pressure mechanical ventilation and have intact bilateral phrenic nerves.
Pre-assignment Detail	One participant had a false positive phrenic nerve test after consent

Arm/Group Title	Treatment
Arm/Group Description	Laparoscopic implantation of 4 NeuRx DPS electrodes and subsequent pacing using the DPS system.
Period Title: Overall Study
STARTED	54
COMPLETED	53
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	NeuRx DPS
Arm/Group Description	Laparoscopic implantation of 4 NeuRx DPS electrodes and subsequent pacing using the DPS system. NeuRx DPS: Laparoscopic implantation of diprapagm electrode and subsequent pacing with the NeuRx DPS.
Overall Participants	53
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.1 (16.9)
Sex: Female, Male (Count of Participants)
Female	12 22.6%
Male	41 77.4%
Region of Enrollment (participants) [Number]
Canada	1 1.9%
United States	50 94.3%
Iceland	2 3.8%
Time since injury (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.425 (6.75)

Outcome Measures

1. Primary Outcome

Title	Enrolled Subjects Achieve Clinically Acceptable Tidal Volume Sustained Over a Continuous 4 Hour Period.
Description	Number of enrolled subjects that successfully maintained clinically acceptable tidal volumes greater than basal requirements over a continuous 4 hour period.
Time Frame	Within one year after implantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Laparoscopic implantation of 4 NeuRx DPS electrodes and subsequent pacing using the DPS system.
Measure Participants	53
Success: Vt>Basal Req. Continuous use > 4 hours	52 98.1%
Partial success: Vt>Basal Req. max use < 4 hours	1 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment
	Comments
	Type of Statistical Test	Other
	Comments	Performance goal of 35%
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Exact two-sided binomial test
	Comments
Method of Estimation	Estimation Parameter	Exact two-sided binomial test
	Estimated Value	96.2
	Confidence Interval	(2-Sided) 95%; 87.0 to 99.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Achieve Clinically Acceptable Basal Metabolic Requirement of Tidal Volume Measured in ml During Chronic Stimulation.
Description	To evaluate the ability of NeuRx DPS therapy to replace mechanical ventilation for patients on a chronic use basis, a secondary indicator of this objective is tidal volume (Vt) measured in ml during chronic stimulation.
Time Frame	Within one year after implantation

Outcome Measure Data

Analysis Population Description

Participants with high level spinal cord injury that are dependent on mechanical ventilation and have intact phrenic nerves.

Arm/Group Title	NeuRx Implanted Patients
Arm/Group Description	SCI patients who received NeuRx DPS implants
Measure Participants	53
Mean (Standard Deviation) [ml]	745.6 (217.7)

3. Secondary Outcome

Title	Number of Patients That Use NeuRx DPS to Breathe Without the Assistance of a Mechanical Ventilator for 24 Continuous Hours a Day
Description	Number of patients that can achieve at least 24 hours daily use of the NeuRx DPS without the assistance of a mechanical ventilator.
Time Frame	Within one year of implantation

Outcome Measure Data

Analysis Population Description

Participants with high level spinal cord injury that are dependent on mechanical ventilation and have intact phrenic nerves.

Arm/Group Title	NeuRx Implanted Patients
Arm/Group Description	SCI patients who received NeuRx DPS implants
Measure Participants	53
Count of Participants [Participants]	31 58.5%

Adverse Events

Time Frame	1 year from date of enrollment
Adverse Event Reporting Description	No details to include
Arm/Group Title	Treatment
Arm/Group Description	Laparoscopic implantation of 4 NeuRx DPS electrodes and subsequent pacing using the DPS system.
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	4/53 (7.5%)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	8/53 (15.1%)
Cardiac disorders
Chest Pain	1/53 (1.9%)	1
Gastrointestinal disorders
Cholecystitis	1/53 (1.9%)	2
General disorders
Death while device was not in use	2/53 (3.8%)	2
Death while device was in use	2/53 (3.8%)	2
Infections and infestations
Elevated Temperature	2/53 (3.8%)	2
Renal and urinary disorders
Urinary Tract Infection	2/53 (3.8%)	2
Acute Polynephritis	1/53 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	3/53 (5.7%)	10
Skin and subcutaneous tissue disorders
Blood from and around treacheostomy tube	1/53 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	38/53 (71.7%)
General disorders
Elevated Temperature	3/53 (5.7%)	6
Pain/Discomfort no device use	3/53 (5.7%)	3
Musculoskeletal and connective tissue disorders
Spasms	5/53 (9.4%)	5
Pain/discomfort with stimulation	3/53 (5.7%)	4
Product Issues
Broken External Wire	7/53 (13.2%)	12
External Equipment Failure	8/53 (15.1%)	10
Broken Anode	6/53 (11.3%)	8
Renal and urinary disorders
Urinary tract infection	6/53 (11.3%)	10
Respiratory, thoracic and mediastinal disorders
Pneumonia	4/53 (7.5%)	7
Aspiration	3/53 (5.7%)	11
Increased secretions	3/53 (5.7%)	3
Low oxygen saturation/tidal volume	3/53 (5.7%)	5
Capnothorax	21/53 (39.6%)	21
Upper Respiratory Infection	5/53 (9.4%)	9
Skin and subcutaneous tissue disorders
Pressure Sore	3/53 (5.7%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.