Evaluation of Oscillation and Lung Expansion (OLE) Using The Volara® System for Treatment of Respiratory Complications in Patients With Neuromuscular Disease in the Home Setting
Phase: NA
Conditions: Neuromuscular Diseases
Sponsor: Baxter Healthcare Corporation

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 1 of 41 
 
Protocol Number:   
CR-RR-2020 - 005 
Status:   
 
Rev.      D 
 
Device(s):  
 
The Volara® System 
 
Sponsor:                     
Hill-Rom Company, Inc. 
Two Prudential Plaza, Suite 4100 
180 N. Stetson Avenue 
Chicago, IL 60601 
 
Sponsor Contact(s):  
 
 
 
Hillrom Company, Inc. 
1020 West County Road F 
Saint Paul, MN  55126 
 
 
 
 
 
Protocol Revision History 
Amendment Number Revision  
Date 
Rationale 
Details 
Not Applicable 
Rev. A 
25May2021 
First release of Protocol  
NA 
1 
Rev. B 
28Jul2021 
Clarify exclusion criteria and 
include minor verbiage 
clarifications throughout 
See Summary of Changes Table below 
2 
Rev. C 
02December2021 
Add exclusion criteria for 
patients requiring continuous 
home mechanical ventilation 
Clarify exclusion for 
anticipated hospitalization to 
“respiratory related 
hospitalization” 
Clarify exclusion for Use of 
OLE therapy in the past 12 
See Summary of Changes Table below 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 2 of 41 
 
months to “Home use of OLE 
therapy” 
Clarify Sponsor’s responsibility 
for devices – Omit language 
suggesting delivery to 
investigators 
Minor verbiage clarification in 
Section 3.2.2 
3 
Rev. D 
11May2022 
Clarify inclusion criteria to 
specify that study patients are 
patients with neurological 
disorders or neuromuscular 
disease 
 
Clarify requirements for 
completing pulmonary 
function testing – allow for 
patients that cannot complete 
all pulmonary function tests to 
participate in the study. 
Require documentation of 
tests not completed 
See Summary of Changes Table below
 
 
 
 
 
 
 
 
 
 
Summary of Changes Table 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 3 of 41 
 
Amendment 2 (02 December 2021) 
 
Section Number   
and Name 
Description of Change  
Brief Rationale 
Protocol Synopsis & 
3.2.2 Exclusion 
Criteria 
In the Exclusion Section, add 
“Requirement for continuous mechanical 
ventilation”  
 
Sponsor has decided to limit 
this initial study to application 
of therapy in non-ventilated 
patients due to the complexity 
of device interaction with 
mechanical ventilators.   
Protocol Synopsis & 
3.2.2 Exclusion 
Criteria 
In the Exclusion Section, clarify exclusion 
for anticipated hospitalization to 
“respiratory related hospitalization” 
Clarify exclusion and not 
exclude patients who may have 
planned hospitalizations for 
non-respiratory procedures 
Protocol Synopsis & 
3.2.2 Exclusion 
Criteria 
In the Exclusion Section, clarify exclusion 
for Use of OLE therapy in the past 12 
months to “Home use of OLE therapy” 
 
Clarify exclusion and not 
exclude patients who may 
have used OLE in the 
hospital 
6.2 Sponsor’s 
Responsibilities 
Clarify Sponsor’s responsibility for devices 
– Omit language suggesting delivery to 
investigators 
Devices will not be 
delivered to investigators 
in this study 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 4 of 41 
 
Section 3.2.2 
Exclusion Criteria 
In the Exclusion Section, clarify language 
for exclusion “Diagnosed with rapidly 
progressing NMD such as certain types of 
Motor Neuron Disease (MND)” 
 
Provide consistent 
language between 
Synopsis and Section 3.2.2 
Exclusion Criteria 
 
Amendment 3 (11May2022) 
Section Number   
and Name 
Description of Change  
Brief Rationale 
Protocol Synopsis & 
3.2 Study 
Population 
Study Population is revised, defined as:  
Patients with neurological disorders or 
neuromuscular disease (NMD) 
 
Neurological disorders and 
neuromuscular disease often 
have similar pulmonary disease. 
“Neurological Disorders” was 
added to expand eligibility of 
patients that have 
neurologically related 
pulmonary complications and 
may not have neuromuscular 
weakness disorders. 
Protocol Synopsis & 
3.2.1 Inclusion 
Criteria 
In the Inclusion Criteria Sections, define 
Inclusion Criteria as:  Documented 
diagnosis of neurological disorder or 
neuromuscular disease (NMD) 
 
 
Neurological disorders and 
neuromuscular disease often 
have similar pulmonary disease. 
“Neurological Disorders” was 
added to expand eligibility of 
patients that have 
neurologically related 
pulmonary complications and 
may not have neuromuscular 
weakness disorders. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 5 of 41 
 
1.3 Rationale for 
Proposed Study 
Include language that describes the 
population as patients with neurological 
disorders or neuromuscular disease 
(NMD) 
Clarify the population being 
enrolled and the rationale for 
including both “Neurological 
disorders and neuromuscular 
disease.” 
3.3.3.3
Under description of pulmonary function 
testing, add language that allows for 
participation in cases where subjects 
(because of their disorder or disease) 
cannot complete all of the pulmonary 
function tests. 
Many patients with neurological 
disorders or neuromuscular 
disease do not have the 
strength or may not have the 
coordination to complete some 
pulmonary function tests 
 
Investigator Signature Page  
 
Investigator Agreement 
 
I agree to conduct this study in accordance with the design and specific provisions of this protocol.  Modifications to the study are 
acceptable only with a mutually agreed upon protocol amendment.   
 
I agree to await Institutional Review Board approval for the protocol before initiating the study, to obtain consent from subjects (unless 
waived) prior to their enrollment (if required) in the study, to collect and record data as required by this protocol and case report forms, 
to prepare adverse event and study reports as required by this protocol and to maintain study documentation for the period of time 
required. 
 
I acknowledge that I am responsible for overall study conduct. I agree to personally conduct or supervise the described study. 
I agree to ensure all associates, colleagues and employees assisting in the conduct of the study are informed about their obligations. 
Mechanisms are in place to ensure that site staff receive the appropriate information throughout the study. 
 
 
Printed Name: 
Investigator Signature: 
 
 
Date: 
 
 
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 6 of 41 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Synopsis 
 
Protocol Title: Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System 
for treatment of respiratory complications in patients with neuromuscular 
disease in the home setting 
Protocol 
Number: 
CR-RR-2020-005 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 7 of 41 
 
Device 
Name(s):  
The Volara® System 
Sponsor: 
Hill-Rom Company, Inc.
Two Prudential Plaza, Suite 4100 
180 N. Stetson Avenue 
Chicago, IL 60601
Objective(s):   
Evaluation of the impact of Oscillation and Lung Expansion (OLE) therapy to 
treat respiratory complications of neuromuscular disease patients 
Endpoints: 
Primary Endpoint:   
● Frequency of exacerbations of pulmonary disease requiring medical 
intervention (e. g. one or more of the following):1 
o Hospitalization 
o ED Visit 
o Unscheduled Antibiotics for Respiratory Infection 
o Unscheduled outpatient visit 
 
Secondary Endpoints:   
● Pulmonary function tests  
o Slow Vital Capacity (SVC) 
o Peak Cough Flow (PCF) 
o Resting Oxygen Saturation (SPO2) 
o Maximal Inspiratory Pressure (MIP) 
● Number of individual hospitalizations 
● Number of inpatient hospital days 
● Number of ICU admissions  
● Number of ICU days 
● Number of outpatient visits for pulmonary complication (Unscheduled 
Physician’s office, Urgent Care Visits, ED visits) 
● Number of antibiotic use days during episodes of pneumonia 
o IV antibiotic days 
o Oral antibiotic days 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 8 of 41 
 
o Nebulized antibiotic days 
● Mean adherence to prescribed treatment regimen 
● Quality of Life (QOL) Assessment 
● Patient/caregiver satisfaction with therapy  
Study Design:  The study will be a non-blinded pre-post intervention study with all subjects 
receiving OLE therapy with The Volara® System 
Study 
Conduct: 
The study will be conducted as a decentralized, home-based study recruiting 
patients from six to ten (6-10) sites in the US. 
Treatment  
of Subjects: 
Enrolled subjects will receive OLE therapy with The Volara® System, following 
the labeled instructions for the device. The prescribed airway clearance 
therapy regimen including duration of therapy will be documented. 
A retrospective chart review will be done for each enrolled subject to 
document incidence of pulmonary exacerbations in the 12 months prior to 
OLE therapy initiation. 
 
Duration of 
Subject 
Participation: 
Each study subject will be treated with OLE therapy as their primary airway 
clearance modality and will remain in the study for a period of approximately 
seven (7) months. 
Number of 
Subjects: 
A total of approximately 70 subjects will be enrolled. 
Study 
Population: 
Patients with neurological disorders or neuromuscular disease (NMD) will be 
enrolled in the study including (but not limited to): 
● Quadriplegia/Spinal Cord Injury (SCI) 
● Slow Progressing, Bulbar Onset, Amyotrophic Lateral Sclerosis (ALS) 
● Muscular Dystrophy (MD) 
● Myotonic Dystrophy 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 9 of 41 
 
● Spinal Muscular Atrophy (SMA) 
● Polio 
● Multiple Sclerosis 
● Diaphragm Disorders 
● Cerebral Palsy 
Inclusion 
Criteria 
Patients who meet all the following inclusion criteria will be included in the 
study: 
● Documented diagnosis of neurological disorder or NMD  
● Age 5-80 years 
● History of one or more respiratory exacerbations in the past 6 months 
or two or more respiratory exacerbations in the past 12 months, which 
required unplanned or unscheduled medical intervention.  
● Ability to perform OLE therapy as directed 
● Signed informed consent (and assent if minor subject) 
Exclusion 
Criteria: 
Patients who meet one or more of the following exclusion criteria will not be 
eligible for the study: 
● Diagnosis with rapidly progressing NMD such as certain types of Motor 
Neuron Disease (MND) 
● Requirement for continuous mechanical ventilation 
● Anticipated requirement for respiratory related hospitalization within 
the next six months 
● History of pneumothorax within past 6 months 
● History of hemoptysis requiring embolization within past 12 months 
● Pregnancy      
● Home use of OLE therapy within the past 12 months 
● Inability or unwillingness to perform OLE therapy or study procedures as 
required      

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 10 of 41 
 
Methods: 
After enrollment, baseline data including demographics, pulmonary related 
medical history including acute respiratory-related hospitalizations, ED visits 
and unscheduled physician office visits, that occurred during the 12 months 
prior to OLE therapy initiation, will be documented. Pulmonary function tests 
(PFTs) will be performed. Quality of Life measures, adherence to therapy and 
satisfaction with therapy data will be collected. 
 
Enrolled patients will be started on OLE therapy with The Volara® System. The 
device will be used within the approved product labeling. This will be the 
primary airway clearance devices for these patients during the 6 months of the 
active-treatment study period. Cough therapy such as mechanical insufflation 
exsufflation (MIE) therapy will be continued if currently prescribed. Other 
treatments such as high-frequency chest wall oscillation (HFCWO) or chest 
physiotherapy (CPT) will not be performed during the active treatment period.
 
Following enrollment, completion of a baseline visit, and initiation of OLE 
therapy, subjects will be seen for 3 follow-up visits. Medical records will be 
reviewed for the 6-month active treatment study period to document the 
occurrence of acute respiratory events, documentation will include respiratory 
related interventions including:  number of hospitalizations and hospitalization 
days, time to first hospitalization, number of courses of antibiotics for 
respiratory complications, number of ICU admissions and ICU days, and number 
of outpatient visits (unscheduled Physician’s office visit, Urgent Care Visits, ED 
visits).  Respiratory support requirements during the active treatment period 
will also be documented. 
  
 
The following tests/procedures will be performed/assessed during the active 
treatment period: 
● Pulmonary function will be assessed to obtain SVC, PCF, SPO2, and MIP.
● A quality-of-life measure will be administered 
● Adherence to the prescribed therapy regimen will be assessed using the 
internal therapy log in The Volara® System. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 11 of 41 
 
● Airway Clearance Satisfaction surveys will be conducted.  
 
Results from the active treatment period will be compared to the baseline 
period, during which the subject received his/her regular airway clearance 
regimen. 
 
Any device related adverse events which occur after initial therapy with The 
Volara® System will be recorded. 
 
Any equipment related complaints which occur after initial therapy with The 
Volara® System will be recorded. 
 
Subject 
Withdrawal: 
Subjects may withdraw consent to participate in the study at any time. The 
subject may also be withdrawn from the study according to investigator 
judgement regarding the continued health or safety of the subject or related 
to inability or unwillingness to perform study therapy or procedures. 
Removal of subjects may occur for any of the following reasons: 
● Subject enrolled in violation of inclusion/exclusion criteria 
● Inability to tolerate OLE therapy 
● Adverse event or adverse device effect that occurs during therapy 
● Physician judgement that the patient is not a good candidate for the 
study 
● Inability or unwillingness to perform OLE therapy and data collection 
maneuvers as directed 
Statistical 
Methods: 
 
Descriptive summary statistics will be provided for demographics, the primary 
and secondary endpoints. Continuous data will be summarized with N, mean, 
median, standard deviation, min, and max.  Categorical data will be summarized 
with the number and percent of patients in each category. 
 
Incidence of adverse device effects (ADEs) will be tabulated. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 12 of 41 
 
Incidence of device-related complaints will be tabulated. 
 
 
1.0 
Introduction 
 
1.1 
Background and Significance 
 
Airway clearance therapy is a key component of the care of many patients with chronic respiratory disease 
including patients with neuromuscular weakness disorders such as muscular dystrophy, spinal muscular 
atrophy or spinal cord injury. With limited respiratory muscle strength and weak expiratory muscles these 
patients often develop pulmonary complications as a result of low lung volume and inability to cough 
effectively.  Airway clearance along with lung expansion and cough therapy are often prescribed in these 
patients to help maintain lung volume and avoid respiratory infections. 
 
The Volara® System provides Oscillation and Lung Expansion (OLE) which consists of continuous positive 
expiratory pressure (CPEP) and continuous high frequency oscillation (CHFO). The therapy is often 
referred to in earlier studies as “CPEP” and “CHFO”. The Volara® device has an internal blower system that 
allows for use of the device in the home as well as the hospital setting. The therapy is designed to assist 
patients that have acute or chronic respiratory disease and require regular airway clearance and/or lung 
expansion therapy. The Volara® System has recently become available for use in the home. However, 
limited data is available evaluating effectiveness of the therapy in this setting. 
 
1.2 
Research Rationale and Supporting Evidence  
 
Though there have been no formal clinical studies of The Volara® System device, evidence from previous 
studies involving earlier OLE devices suggest that this therapy provides effective airway clearance and 
lung expansion in hospitalized patients. Huynh et al. found that post-operative patients treated with OLE 
had fewer pulmonary complications, shorter hospital stay and less required time on mechanical 
ventilation compared to those treated with standard therapy [2]. Patel et al. reported on a randomized 
parallel study comparing outcomes in 32 adult cystic fibrosis (CF) patients with severe pulmonary 
exacerbations and admitted for intravenous (IV) therapy. Patients were randomized to treatment with 
either The MetaNeb® System or The Vest® System for up to 14 days. In this setting, results were positive 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 13 of 41 
 
but comparable to the alternative therapy [3]. Hsieh, et al. evaluated the impact of OLE using The 
MetaNeb® System in a group of anatomic lung resection patients. OLE therapy was compared to 
respiratory therapist driven protocol administered positive airway pressure (PAP) and positive expiratory 
pressure (PEP), the current standard of care. Results showed that OLE therapy resulted in significant 
improvement in vital capacity (VC) over time compared to standard positive pressure devices [4]. Morgan, 
et al. investigated the feasibility, safety and efficacy of CHFO administered via The MetaNeb® System to 
59 invasively ventilated pediatric patients, between 2007-2012. A total of 528 treatments were evaluated.  
Results support safety and feasibility and suggest that CHFO may be beneficial by improving lung 
compliance in patients with secretion-induced atelectasis [5].  
 
More recently, a study of OLE was completed evaluating use of the therapy in a small group of patients, 
including patients with NMD, in the home setting. This study. suggests the therapy was easy to do, 
patients were able to adhere to the treatment regimen and based on patient and caregiver reports, the 
therapy may be effective when used consistently as a primary therapy [6].  
 
1.3 
Rationale for the Proposed Study 
 
Many patients with chronic respiratory disease require regular airway clearance therapy to mobilize 
secretions and to decrease the risk of pulmonary infections. Additionally, some patients (e.g. patients with 
neurological and neuromuscular disease) are prone to developing atelectasis and require therapy to 
maintain lung volume. OLE therapy has been shown in clinical studies and anecdotal reports to provide 
effective airway clearance and lung expansion therapy in a variety of patients in the acute care setting. 
The Volara® System is now available to provide this therapy in the homecare environment. The proposed 
study is intended to evaluate the impact of this therapy in treating patients with a need for daily airway 
clearance and/or lung expansion therapy in the home setting. 
1.4 
 
Study Device and Therapy 
The intervention device use in this study is The Volara® System (Hill-Rom; St. Paul, MN). It is an FDA 510k 
cleared device (k192143), powered by an internal blower, that delivers oscillation and lung expansion 
(OLE) therapy using both continuous high-frequency oscillation (CHFO) and continuous positive 
expiratory pressure (CPEP). The therapy is indicated for mobilization of secretions, lung expansion 
therapy and the treatment and prevention of pulmonary atelectasis. The device can also provide 
supplemental oxygen when used with an oxygen supply.  
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 14 of 41 
 
OLE therapy in the current study may be delivered using      aerosolized medications,      if ordered by the 
subject’s treating physician as part of his/her routine care.       .Aerosolized medications may include, but 
are not limited to: Albuterol Sulfate, Ipratropium Bromide and      Cromolyn Sodium. If no aerosolized 
medications are ordered and/or if the schedule for ordered medications does not align with the 
schedule for OLE therapy, the therapy should be delivered using 0.9% normal saline. OLE therapy should 
be delivered two times per day (e.g. morning and afternoon treatments). Therapy should be delivered 
using a pre-set (10-minute) therapy regimen that includes both CPEP and CHFO therapy.  
 
Cough therapy such as mechanical insufflation exsufflation (MIE) therapy will be continued if currently 
prescribed. Other treatments such as high-frequency chest wall oscillation (HFCWO) or chest 
physiotherapy (CPT) will not be performed during the active treatment period. 
 
2.0 
Study Objectives  
The primary objective of the study is to evaluate the impact of OLE to treat respiratory complications 
of neuromuscular disease patients. The frequency of pulmonary exacerbations and other clinical 
outcome measures will be assessed to determine the effect of consistent OLE therapy. 
3.0 
Study Design 
 3.1 Overview of Study Design   
 
3.1.1 
Design:   
 
The study will be a non-randomized open label pilot study. It is a decentralized study using an 
observational design comparing a retrospective control period to an active treatment period. 
Approximately seventy (70) patients will be enrolled from identified clinics that currently treat NMD 
patients. All enrolled subjects will receive OLE treatment during the active treatment period. 
Subjects will be recruited from six to ten (6-10) sites in the US. 
 
Study subjects will serve as their own control. Medical records will be reviewed for each study 
subject for the twelve-month period prior to initiation of OLE therapy. The study will compare the 
frequency of exacerbations experienced prior to treatment with OLE to the frequency of 
exacerbations experienced in the active treatment period, during which study subjects receive 
treatment with The Volara® System. In addition, specific healthcare utilization indicators including 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 15 of 41 
 
hospitalizations, antibiotic use, and emergency department (ED) visits for pulmonary complications 
will be documented for each study period.  
 
Pulmonary function measures, a quality of life (QOL) assessment and a satisfaction survey will be 
assessed at baseline and compared to results collected during the active treatment period. 
Adherence to OLE therapy will be collected throughout the active treatment period. 
 
3.2 Study Population   
The study population consists of adult and pediatric patients ages 5 to 80 with neurological 
disorder or NMD diagnoses who have a history of respiratory complications associated with 
their neurological disorder or NMD. 
 
3.2.1 Inclusion Criteria   
Patients who meet all the following inclusion criteria will be included in the study: 
● Documented diagnosis of neurological disorder or NMD  
● Age 5-80 years 
● one or more respiratory exacerbations in the past 6 months or two or more respiratory 
exacerbations in the past 12 months, which require unplanned or unscheduled medical 
intervention. 
● Ability to perform OLE therapy as directed 
● Signed informed consent (and assent if minor subject) 
3.2.2 Exclusion Criteria  
Patients who meet one or more of the following criteria will be excluded (or will be exited) from 
the study: 
 
● Diagnosis with rapidly progressing NMD such as certain types of Motor Neuron Disease (NMD) 
● Requirement for continuous mechanical ventilation 
● Anticipated requirement for respiratory related hospitalization within the next six months 
● History of pneumothorax within past 6 months 
● History of hemoptysis requiring embolization within past 12 months 
● Pregnancy 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 16 of 41 
 
● Home use of OLE therapy within the past 12 months 
● Inability or unwillingness to perform OLE therapy or study procedures as required 
 
3.2.3 Stipend for Study Participation  
Patients who participate in the study will receive a stipend for participation. Patients will be paid 
up to $200 in the form of prepaid debit cards worth $50 after each study visit (Baseline, 1-
month, 3-month, and 6-month). 
 
 
 
3.3  Study Observations, Procedures and Evaluation Criteria  
The study is a decentralized trial. All study visits required for the completion of the trial will occur 
in the home or will be done virtually. Eligible subjects will be pediatric and adult patients ages 5 – 
80 who are able to perform OLE therapy using a mouthpiece, mask, or trach adaptor and who 
meet all inclusion and none of the exclusion criteria. Informed consent (and assent if minor 
subject) will be obtained prior to enrollment in the study. Demographic and medical history data 
will be collected from the medical record of each subject at the time of enrollment. 
3.3.1 Informed Consent: 
Informed consent (and assent if minor subject) will be obtained from the patient or legally 
authorized representative prior to enrollment in the study. Informed consent will be obtained by 
the principal investigator or his/her representative.  
  
3.3.2 Selection Criteria:   
Inclusion and exclusion criteria will be reviewed and documented for all study subjects (criteria 
are described in section 3.2 above). 
 
3.3.3 Study Visits and Data Collection Procedures:   
 
All study subjects will complete a virtual home baseline study visit for initiation of the trial and 
enrollment into the study. Following the baseline visit, each study subject will complete three 
follow-up visits. The first follow-up visit will be approximately one month after initiating therapy 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 17 of 41 
 
and will occur virtually or by phone. Follow-up visits two and three will be done virtually and will 
occur approximately three months and six months after initiation of OLE therapy. Pulmonary 
function measures will be collected at baseline and at the end of each month of therapy during 
the active treatment period. Study Visits and procedures for data collection is described below. 
3.3.3.1 
Baseline Study Visit:   During the baseline visit, study staff will review the informed 
consent form (and assent form if minor subject) with the study subject and/or caregiver(s). If 
the patient/caregiver agrees to participate in the study, the informed consent form (and assent 
form, if applicable) will be signed. A pregnancy test will be administered to female subjects of 
childbearing age. Inclusion and exclusion criteria will then be assessed and documented and (if 
eligible) the subject will be enrolled in the study. The study schedule and subject responsibilities 
will then be reviewed with the subject/caregiver. During the Baseline Visit, the subject’s current 
respiratory therapy regimen and required respiratory support will be documented. A quality of 
life (QOL) assessment using the Severe Respiratory Insufficiency (SRI) questionnaire will be 
completed for each subject to assess QOL rating during the pre-treatment period and a 
Satisfaction Survey questionnaire will be completed by the subject and/or caregiver as an 
assessment of the current therapy regimen. 
3.3.3.2 
Documentation of Demographics, Medical History and Pulmonary Exacerbations:  
Demographic data will be collected for patients enrolled in the study. Medical records for each 
enrolled subject will be obtained and reviewed to obtain relevant patient medical history and to 
document pulmonary comorbidities and history at the time of enrollment. Current respiratory 
related medications and treatments will be documented. Pulmonary exacerbations (as defined in 
the study endpoints) that occurred in the 12-month period prior to enrollment in the study will 
be documented. Subsequent medical records will be obtained during the active treatment period 
and will be used to determine and to document the occurrence of pulmonary exacerbations 
during that period. 
● Demographic Data  
The following demographic data will be collected: Age, Height, Weight, Race, Ethnicity 
and Gender.  
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 18 of 41 
 
● Pulmonary Related Medical History 
History of asthma, cystic fibrosis, bronchiectasis, COPD, obstructive sleep apnea, 
documented obesity (BMI > 30 kg m2), other pulmonary condition(s) will be 
documented. 
 
● Medications 
Respiratory related medications such as bronchodilators, or mucolytics that are 
prescribed for each study subject during the 12-month pre-treatment period, as well 
as respiratory medications that are prescribed during the active treatment period will 
be documented. 
 
● Respiratory Status 
Respiratory status including required respiratory support (e.g., invasive mechanical 
ventilation, noninvasive ventilation, requirement for tracheostomy, O2 level, etc.) will 
be documented from the patient medical record for each subject.  
 
● Respiratory Treatments 
Respiratory treatments, including mechanical insufflation/exsufflation or other lung 
expansion or airway clearance therapy, or other therapies to improve respiratory 
status will be documented from the patient medical record. 
   
● Pulmonary Exacerbations  
Pulmonary exacerbations (as defined in the study endpoints) which occurred during 
the 12-month pre-treatment period or during the active treatment period will be 
documented. 
 
3.3.3.3 
Pulmonary Function Testing:  Pulmonary function testing will be completed virtually by 
an external research organization which specializes in home pulmonary function testing 
(Zephyrx). This testing will be scheduled separately following enrollment into the study. Baseline 
parameters will be assessed, including slow vital capacity (SVC), Peak Cough Flow (PCF), Resting 
SpO2, and Maximal Inspiratory Pressure (MIP). With this study population, certain subjects may 
not be able to complete a valid test for all pulmonary function procedures. If unable to complete, 
a procedure, the inability to complete that procedure will be documented. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 19 of 41 
 
3.3.3.4   Run-in Period:  Following the Baseline Study Visit, a run-in period of two to four weeks 
will be completed by the subject prior to initiation of OLE therapy. During this period, the 
subject/caregiver will document use of MIE and other current airway clearance and lung 
expansion therapy/maneuvers for each day in the run-in period. 
3.3.3.5 
Home Training on The Volara® System:  A Hillrom designated trainer will set up the 
device and review operation and treatment protocol at the time the device is delivered. Study 
subjects and caregivers will be instructed to use the device as their primary airway clearance and 
lung expansion therapy for a period of six months. Hillrom training staff will follow up with each 
Volara user according to the standard device placement and follow-up program. 
3.3.3.6 
Adherence Documentation:  During the six-month follow-up period, adherence to the 
daily prescribed therapy regimen will be assessed. The Volara® System logs therapy details for 
each therapy completed, including the total time of therapy, the number of stages completed, 
the total time in CPEP mode, total time in CHFO mode and peak pressures achieved in each mode. 
Adherence data logs will be downloaded on a regular basis during the active treatment period. 
 
3.3.3.8 
One-month Virtual Study Visit:  A one-month study visit with each study subject will be 
conducted virtually. Visits will be completed +/- 3 days from the one-month scheduled visit date. 
During this visit, the following procedures and assessments will be conducted: 
 
● Review of study procedures with subject/caregiver  
● Review of current respiratory status, respiratory treatments, and medications 
● Documentation of patient/caregiver reported exacerbations and medical interventions 
for the prior period (run-in and first month of Volara therapy) 
● Documentation of any Adverse Device Effects that the subject experienced during the 
follow-up period 
● Completion of QOL questionnaire 
● Completion of Patient/Caregiver Satisfaction survey 
 
3.3.3.9 
Three-month and Six-month Virtual Study Visits:  Three-month and six-month study 
visits with each study subject will be conducted virtually by study staff. Visits will be completed 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 20 of 41 
 
+/- 3 days from the one-month scheduled visit date. During these visits, the following procedures 
and assessments will be conducted: 
 
● Review of study procedures with subject/caregiver  
● Review of current respiratory status, respiratory treatments, and medications 
● Documentation of patient/caregiver reported exacerbations and medical interventions 
for the prior period (three-months of Volara therapy) 
● Completion of QOL questionnaire 
● Completion of Patient/Caregiver Satisfaction survey 
 
3.3.3.10 Monthly Pulmonary Function Measure Visit:  Monthly virtual visits with each study 
subject will be conducted virtually in the subject’s home by the pulmonary function specialists. 
Visits will be completed +/- 3 days from the one-month scheduled visit date. During these visits, 
the following procedures and assessments will be conducted: 
 
● Slow Vital Capacity (SVC) 
● Peak Cough Flow (PCF) 
● Resting O2 Saturation (SpO2) 
● Maximal Inspiratory Pressure (MIP) 
 
 
3.3.4 Evaluation Criteria  
The active treatment therapy regimen (which includes OLE therapy with The Volara® System) 
will be evaluated to determine the effect on the frequency of pulmonary exacerbation and/or 
change in other clinical endpoints during the active treatment (OLE therapy) period. Endpoints 
are described below: 
 
3.3.4.1  
Primary Endpoint(s): 
 
● Frequency of exacerbations of pulmonary disease 
Exacerbations of pulmonary disease are defined as changes in respiratory status requiring 
intervention. Documentation of pneumonia or respiratory infection, change in chest x-ray, 
changes in requirement for respiratory support necessitating any of the interventions below 
will be considered an exacerbation of pulmonary disease: 
o Hospitalization 
o Emergency Department (ED) Visit 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 21 of 41 
 
o Antibiotics (oral, intravenous, or nebulized) 
o Unscheduled Outpatient Clinic Visit 
 
3.3.4.2 
Secondary Endpoint(s):  
 
 
 
● Hospital Admissions 
Total number of Hospital Admissions will be determined for each study subject by review of 
the medical record for pre-treatment period and for the active treatment period. Total Hospital 
Admissions will be determined for each subject and for the study group (Mean + SD) for each 
study period. 
 
● Hospital Length of Stay 
Total Hospital Length of Stay will be determined for each study subject by calculating the 
number of days spent in the hospital for each admission, from time of admission to time of 
discharge. The sum of all hospital days for each subject will be calculated for the pre-treatment 
period and for the active treatment period. Total Hospital Days will be determined for each 
subject and for the study group (Mean + SD) for each study period. 
 
● ICU Admissions 
Total number of ICU Admissions will be determined for each study subject by review of the 
medical record during the pre-treatment period and for the active treatment period. Total ICU 
Admissions will be determined for each subject and for the study group (Mean + SD) for each 
study period. 
 
● ICU Length of Stay 
Total ICU Length of Stay will be determined for each study subject by calculating the number 
of days spent in the ICU for each admission, from time of admission to time of discharge. The 
sum of all ICU days for each subject will be calculated for the pre-treatment period and for the 
active treatment period. Total ICU Days will be determined for each subject and for the study 
group (Mean + SD) for each study period. 
 
● Number of Outpatient Visits 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 22 of 41 
 
Total number of Outpatient Visits will be determined for each study subject by review of the 
medical record and identifying all visits defined as 1) physician office visits, 2) urgent care visits 
or 3) emergency department (ED) visits for pulmonary complications that occur during the pre-
treatment period and during the active treatment period. Total Outpatient Visits will be 
determined for each subject and for the study group (Mean + SD) for each study period. 
 
● Number of Antibiotic Use Days 
Total number of Antibiotic Use Days for pulmonary exacerbation will be determined for each 
study subject by review of the medical record and by calculating the number of days of 
antibiotic use for each episode, from time of initiation to time of discontinuation. Antibiotic 
use will be further categorized and individual totals provided for 1) oral, 2) intravenous, and 3) 
nebulized antibiotic use for pulmonary complications that occur during the pre-treatment 
period and during the active treatment period. Total antibiotic days and totals for sub-
categories will be determined for each subject and for the study group (Mean + SD) for each 
study period. 
 
● Pulmonary Function Testing:  Spirometry Measures, Oxygen Saturation and Maximal 
Inspiratory Pressure 
Subject Pulmonary Function will be assessed at baseline and monthly during the active 
treatment period. Virtual visits will be conducted by pulmonary function specialists, as 
described above. The following measures will be collected: 
 
o Slow Vital Capacity (SVC) 
o Peak Cough Flow 
o Resting SpO2 
o Maximal Inspiratory Pressure (MIP)  
 
Baseline measures will be compared to measures obtained during the active treatment period. 
 
● Quality of Life (QOL) Assessment 
The Severe Respiratory Insufficiency (SRI) questionnaire will be administered to all study 
subjects by the study staff at baseline (reflecting pre-treatment therapy regimen) and during 
one-month, thee-month and six-month study visits. Results will be determined for each subject 
and for the study group for each time period and will then be compared to determine any 
differences in QOL scores between the pre-treatment and active treatment time periods. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 23 of 41 
 
 
● Adherence to OLE Treatment Regimen 
Adherence to the OLE treatment regimen will be determined by downloading device therapy 
log data during the active treatment period.      Total adherence to the OLE treatment regimen 
will be determined for each subject and for the study group (Mean + SD) for the active 
treatment period. 
 
● Patient/Caregiver Satisfaction with Therapy 
A satisfaction questionnaire will be administered to all study subjects/caregivers by the study 
staff at baseline (reflecting the patient’s pre-treatment therapy regimen) and at each 
subsequent study visit to assess satisfaction with OLE therapy. Results will be determined for 
each subject and for the study group for each time period and will then be compared to 
determine any differences in satisfaction scores between the pre-treatment and active 
treatment time periods. 
 
3.3.4 Study Exit Documentation  
Study exit data is collected to document the reason participation in the study ended. Reasons 
for exit from the study include:  
o Completion of the study 
o Subject inability to tolerate therapy  
o Subject withdrawal 
This may be voluntary withdrawal on the part of the subject or subject caregiver or 
withdrawal by investigator for subjects deemed unfit for or unsafe to continue the trial 
o Subject death 
3.3.5 Study Observations/Procedures Table   
 
 
The study observations and documentation timeline are outlined in Table 1.  

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 24 of 41 
 
TABLE 1 
Study Observations/Procedures 
Procedures 
Baseline 
Run-in 1 month 3 months 6 months
Inclusion/Exclusion Criteria 
X 
 
 
 
 
Pregnancy test (women of childbearing age) 
X 
 
 
 
 
Informed consent (and assent if minor subject) 
X1 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Baseline Pulmonary Medications 
X 
 
 
 
 
Documentation of acute pulmonary 
exacerbations: 
● 
Hospital admission and discharge (including 
ICU admission and discharge) 
● 
Antibiotic use (IV/Oral/inhaled) start and stop 
dates 
● 
Outpatient Visits for Pulmonary Complication
o 
Physician Office Visits 
o 
Urgent Care Visits 
o 
ED Visits 
Documented from the medical record 
X 
Retrospective 
(past 12 mo) 
 
X 
Active Treatment Period 
QOL Questionnaire 
X 
 
X 
X 
X 
Patient/Caregiver satisfaction with Therapy 
X 
 
X 
X 
X 
Basic Pulmonary Function Measures 
● 
SVC 
● 
PCF 
● 
Resting SpO2 
● 
Maximal Inspiratory Pressure (MIP) 
X 
 
 
Monthly 
 
Adherence to prescribed regimen (OLE) 
 
 
Ongoing       
Documentation of use of MIE or other airway 
clearance/lung expansion therapy/maneuvers 
 
X 
 
Adverse device effects 
 
 
Each Occurrence 
Study Exit Form 
 
 
 
 
X 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 25 of 41 
 
1Obtained prior to any study-specific procedures 
 
3.3.6 Study Flow and Timeline   
 
 
The study flow and timeline of events and data collection periods is shown below in and Figure 1.  
 
FIGURE 1 
 
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 26 of 41 
 
3.5 
Statistical Methods and Analysis  
 
 
3.5.1 
Sample Size Estimation   
The sample size for this study is a convenience sample. Resulting data on the 
outcomes associated with the OLE may provide preliminary data on effectiveness of 
therapy and help to provide definition of the effect size and variability and the number 
of subjects required for subsequent studies.  
 
 
3.5.2 
Statistical Analysis   
• Summary statistics and data listings will be provided. 
 
• Demographic data will be summarized.  For continuous type data (e. g. Age), 
descriptive summary statistics (N, mean, median, standard deviation, min, and max) 
will be presented. For categorical variables (gender, race, etc.) the number and 
percent of subjects in each category will be provided. 
 
• Endpoints will be documented and compared as described below: 
 
Primary Endpoints: 
Frequency of Exacerbation of Pulmonary Disease (as defined in section 3.3.4.1) 
along with 95% confidence interval will be generated.  A detailed description of the 
analysis plan along with specific subsets to be summarized will be described in a 
separate document (the statistical analysis plan). 
 
Secondary Endpoints: 
The secondary endpoints (listed in section 3.3.4.2) will be summarized with 
descriptive summary statistics appropriate for continuous or categorical data, 
depending on the outcome being summarized: 
 
1. Hospital Admissions 
2. Hospital LOS 
3. ICU Admissions 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 27 of 41 
 
4. ICU LOS 
5. Number of Outpatient Visits 
6. Antibiotic Use Days 
7. Pulmonary Function Testing 
● SVC 
● PCF 
● Resting SpO2 
● MIP 
8. QOL Assessment 
9. Adherence to OLE Therapy Regimen 
10. Patient/Caregiver Satisfaction 
Comparison of Pre-treatment and Active Treatment Periods 
Rate of exacerbation and heath care utilization will be evaluated to compare the 
active treatment period and the control periods (six-month period immediately 
prior to active treatment and six-month seasonally equivalent time-period). 
Remaining endpoints will compare baseline assessments to assessments obtained 
during the active treatment period. Comparisons will be conducted for the purpose 
of identifying any statistical associations that can be attributed to use of OLE 
treatment with The Volara® System.  
General Study Information 
 
4.1 Technical Support for Device(s) 
 
 
Technical support will be performed by Hillrom following routine service practices (contact 
details will be provided). 
 
4.2 Record Retention 
 
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 28 of 41 
 
Records must be maintained for a period of up to three years after the latter of the 
following dates:  the date the study is completed/terminated, or the date of the last 
regulatory approval.  The Investigators or Institutions shall notify the Sponsor at least thirty 
(30) days prior to any planned destruction of records from this study. 
 
 
All records will be kept confidential and the patient’s name will not be released at any time. 
Code numbers will be used to de-identify patient information on the CRFs and other study-
related documents. 
 
5.0 
Safety and Device Complaint Definitions and Reporting Requirements  
 
Safety surveillance within this study and the safety reporting both performed by the 
investigator, starts as soon as the subject signs informed consent (and assent if minor 
subject) and receives the first study-specific treatment. The safety surveillance and the 
safety reporting will continue until the last study-specific test has been performed, the 
subject/investigator concludes his participation into the study or the subject/investigator 
withdraws the subject from the study, except as otherwise specified in the protocol. 
Reportable events: 
 
(1) Adverse Device Effects (adverse event related to the device) associated with 
the use of The Volara® System 
 
(2) Device Complaints associated with The Volara® System  
 
During the study, safety events and device complaints must be reported to the Sponsor 
within 24 hours of becoming aware of the event. Please contact 
 by phone: 
 or email:  
 
.  
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 29 of 41 
 
A complaint is defined as any written, electronic or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of the device after its release for distribution (21 CFR 820.3(b)). 
 
Any device Complaint and/or reported safety event be reviewed, evaluated, and 
investigated by Hillrom and reported to the appropriate Health Authority per current 
regulations.  
Additional information may be requested, when required, by the Sponsor in order to 
support the reporting of safety events to regulatory authorities. 
The investigator must notify the IRB/EC, if appropriate, in accordance with national and 
local laws and regulations, of the safety and/or complaint events reported to the Sponsor. 
 
5.1 Foreseeable Risks and Benefits of the Clinical Study 
 
5.1.1 Anticipated risks associated with study participation include, but are not limited 
to: 
 
● Hyperventilation  
● Decreased cardiac output 
● Headache 
● Increased air trapping 
● Pulmonary air leak 
● Pneumothorax 
● Pulmonary hemorrhage  
There may be other risks or discomforts associated with receiving this therapy 
which are currently unforeseen. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 30 of 41 
 
5.1.2 Possible benefits of study participation include, but are not limited to: 
 
● Information learned about use of OLE therapy in patients with NMD in this 
study may help doctors learn more about treating patients with the same 
condition in the future. 
● Study participation may contribute to improving the health of patients with 
NMD. 
● It is possible that there will be no benefit from study participation. 
 
5.2 Adverse Event (AE) Definition  
 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in subjects, users or other persons, whether 
or not related to the investigational medical device under study. 
This definition includes events related to the investigational medical device. 
This definition includes events related to the procedures involved. 
 
5.3 Serious Adverse Event (SAE) Definition  
 
An adverse event that led to: 
● Death 
● A serious deterioration in the health of the subject, that either resulted in: 
o A life-threatening illness or injury OR 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 31 of 41 
 
o A permanent impairment to a body structure or a body function OR 
o An in-patient or prolonged hospitalization OR 
o A medical or surgical intervention to prevent life-threatening illness or injury 
or permanent impairment to a body structure or a body OR 
o A malignant tumor 
● Fetal distress, fetal death or a congenital abnormality or birth defect 
● A planned hospitalization for a pre-existing condition, or a procedure required by 
the protocol is not considered a serious adverse event. 
 
5.4 Adverse Device Effect (ADE) Definition  
 
An adverse event related to the use of an investigational medical device. 
This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device. 
This definition includes any event resulting from the use error or from intentional misuse 
of the investigational medical device. 
 
5.5 Serious Adverse Device Effect (SADE) Definition  
 
Adverse device effect that has resulted in any of the consequences characteristic of a 
serious adverse event. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 32 of 41 
 
5.5.1 Unanticipated Serious Adverse Device Effect (USADE) Definition  
A serious adverse device effect which by its nature, incidence, severity or outcome 
has not been identified in the current version of the risk analysis report. 
1. UADE [applicable to investigational studies following FDA regulations] 
As defined in 21 CFR §812.3, unanticipated adverse device effects (UADE) are 
defined as any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, problem, 
or death was not previously identified in nature, severity, or degree of incidence in 
the clinical investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device 
that relates to the rights, safety, or welfare of subjects.   
If an unanticipated adverse device effect occurs, the investigator must notify 
Hillrom and the IRB/EC immediately, but no later than 10 working days of the 
investigator’s knowledge of the event, as required by 21 CFR §812.150. Hillrom will 
take any steps necessary to investigate the event and will be responsible for 
notifying FDA and all other participating IRBs/ECs and investigators. 
5.5.2 Anticipated Serious Adverse Device Effect (ASADE) Definition  
A serious adverse device effect which by its nature, incidence, severity or outcome 
has been previously identified in the risk analysis report. 
5.6 Subject Death  
 
All subject deaths are to be documented and reported to the sponsor within 72 hours 
after becoming aware of the event. 
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 33 of 41 
 
5.7  Complaint or Device Deficiency Definition  
 
A complaint is defined as any written, electronic or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of the device after its release for distribution (21 CFR 820.3(b)). 
Any device complaint and/or allegation of injury shall be reviewed, evaluated, and 
investigated by Hillrom Post Market Surveillance and reported to the appropriate Health 
Authority per current regulations. The Investigators are responsible for informing the 
Institutional Review Boards, as per their guidelines. 
6.0 
Investigator, Sponsor, and IRB/EC Responsibilities 
 
6.1   Investigator’s Responsibilities 
 
The Investigator will comply with Good Clinical Practices (GCPs) and applicable regulatory 
requirements, as itemized below. 
● The Investigator shall be familiar with the appropriate use of The Volara® System 
and any other information provided by the Sponsor. 
 
● The Investigator shall provide adequate staff to conduct and complete the study 
within the agreed study time period. The Investigator shall ensure that all persons 
assisting with the study are adequately informed about the protocol, The Volara® 
System and their study related duties. 
 
● A qualified physician delegated as the Investigator will be responsible for all study 
related duties and functions. During a subject’s participation, the 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 34 of 41 
 
Investigator/Institution shall ensure that adequate medical care is provided to the 
patient for any adverse event. 
 
● The Investigator shall have written and dated approval from the IRB/EC for the 
protocol, informed consent and assent forms or waiver of informed consent, 
HIPAA authorization, patient recruitment procedures and any other written 
information for the conduct of the study and/or to be provided to patients. 
 
● The Investigator/Institution shall conduct the study in compliance with the 
protocol agreed to by the Sponsor. The Investigator shall sign the protocol or 
alternative contract to confirm agreement. The Investigator shall not implement 
any deviation or changes to the protocol without agreement with the Sponsor and 
prior review and agreement from the IRB/EC, unless the deviation or change is to 
eliminate an immediate hazard to study patients. 
 
● The Investigator/Institution shall maintain subject confidentiality. 
 
●  In obtaining and documenting informed consent (and assent if minor subject), the 
Investigator must comply with the applicable regulatory requirements and shall 
adhere to GCP and the ethical principles that have their origin in the Declaration of 
Helsinki. 
 
● The Investigator, per Title 21 Code of Federal Regulations Part 54, shall disclose 
any financial interests that could affect the reliability of the data. 
 
● The Investigator shall ensure the accuracy, completeness, legibility and timeliness 
of the data reported to the Sponsor in the CRFs and required reports. 
 
● The Investigator shall maintain the study documents as required by the applicable 
regulatory requirements. Records must be maintained for a period of three years 
after the latter of the following dates:  the date the study is completed/terminated 
or the date of the last regulatory approval based on the study data. The 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 35 of 41 
 
Investigator or Institution shall notify the Sponsor at least thirty (30) days prior to 
any planned destruction of records from this study. 
 
● The Investigator shall submit written summaries of the status of the study to the 
IRB/EC annually, or as requested by the IRB/EC, and upon completion of the Study. 
 
● All serious adverse device effects (SADE) and unanticipated adverse device effects 
(UADE) shall be reported immediately to the Sponsor and per the local IRB/EC’s 
reporting policy at that site. The initial reports shall be followed by more detailed 
reports if more information becomes available. If the study is terminated 
prematurely or suspended for any reason, the Investigator shall promptly inform 
the study patients and ensure appropriate therapy and follow-up is scheduled or 
documented for each patient. 
 
6.2    Sponsor’s Responsibilities 
 
The Sponsor of the program is Hillrom Company, Inc. The Sponsor’s, responsibilities are 
itemized below. 
● The Sponsor is responsible for implementing and maintaining quality assurance 
and quality control systems with written standard operating procedures (SOPs) to 
ensure that studies are conducted and that the data are generated, documented, 
and reported in compliance with the protocol, GCPs and applicable regulatory 
requirements. The Sponsor is responsible for securing an agreement from all 
involved parties to ensure direct access to all study-related sites, source 
documents, and reports for the purpose of monitoring and auditing. 
 
● The Sponsor may transfer any or all of the study-related duties and functions to a 
Contract Research Organization (CRO), but the ultimate responsibility for the 
quality and integrity of the data resides with the Sponsor. 
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 36 of 41 
 
● The Sponsor shall use an unambiguous patient identification code that allows for 
de-identification of all the data reported for each patient. 
 
● The Sponsor shall retain the essential documents as required by the applicable 
regulatory requirements. Records must be maintained for a period of three years 
after the latter of the following dates:  the date the study is completed/terminated 
or the date of the last regulatory approval.   
 
● The Sponsor shall ensure the Investigator(s) selected for the study have the proper 
qualifications, training, and resources to perform the study adequately. 
 
● The Sponsor shall provide the Investigator(s) with a protocol and an Investigator 
Brochure (or equivalent documentation) and allow sufficient time for the 
Investigator to review the information provided. 
 
● The Sponsor shall ensure timely delivery of the Device(s); maintain records that 
document shipment, receipt, disposition, return and destruction (if applicable) of 
the Devices; maintain a system for retrieving Devices and documenting this 
retrieval; maintain a system for the disposition of unused Device(s) and for the 
documentation of this disposition. 
 
● The Sponsor shall ensure that it is specified in the protocol or other written 
agreement that the Investigator(s)/Institution(s) provide direct access to source 
documents for study-related monitoring, audits, IRB/EC review, and regulatory 
inspection. The Sponsor shall verify that each patient has consented in writing, to 
direct access to his/her original medical records for study-related monitoring, 
audit, IRB/EC review and regulatory inspection, or that informed consent has been 
waived. 
 
● The Sponsor is responsible for submitting reports of all recalls and device 
disposition to the IRB/EC and the FDA, as applicable. 
 
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 37 of 41 
 
6.3    Institutional Review Board (21 CFR Part 56) / Ethics Committee  
 
● Prior to study initiation, the appropriate IRB/EC must review and give written 
approval for the study and provide the approved informed consent form.  It is the 
responsibility of the Investigators, in collaboration with the Sponsor, to provide 
the IRB/EC with all necessary information to satisfy the individual Institution’s 
requirements. 
 
● Informed consent must be obtained from all subjects, or legally authorized 
representative, prior to participation as per Federal Regulations and/or the 
qualifying Institutional Review Board (IRB) or Ethics Committee (EC). A blank copy 
of the IRB/EC-approved form must be kept on-site site and by the sponsor.  The 
signed original for each subject must be kept in the subjects will be given a copy of 
their signed informed consent. 
 
7.0 
Administrative Study Information 
 
 
 
 
7.1    Pre-Study Site Visits (Qualification and Site Initiation Visits) 
The Sponsor will confirm the site’s ability to perform the study, store study equipment, 
and recruit patients. This is typically done during a visit to the site to meet with the 
Investigator(s), but may be done remotely in certain circumstances.    
 
7.2    Investigator Records and Reports 
Where required by applicable regulatory requirements, an investigator signatory will be 
obtained for the acceptance of the clinical study report. The Investigator(s) will be 
provided reasonable access to statistical results and tables and will be provided a 
summary of the study results. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 38 of 41 
 
 
7.3    Interim Monitoring and Closeout Visit(s) 
In-person and/or remote interim monitoring and close-out visits may be conducted by 
the Sponsor for quality assurance. 
 
7.4    Materials Provided by the Sponsor 
The Sponsor will supply The Volara® System devices (as required) and as agreed upon in 
the study agreement.   
 
8.0 
Changes Necessary after Study Initiation   
 
If there are changes to the study plan or protocol, these changes will be agreed upon by 
the Sponsor, its acting representative (if appropriate), the Investigator(s), and the 
IRB/EC before the changes are implemented.  All changes must be documented. 
 
9.0 
Study Completion 
 
See section 3.3 for study visit details.  Upon completion of the study, a study exit form 
will be completed for each patient. 
 
10.0 
Confidentiality/Publication of the Study 
 
Any information shared by the Sponsor regarding this clinical study is the property of 
the Sponsor. This protocol is considered proprietary information and should be kept 
confidential. 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 39 of 41 
 
Ownership and guidelines for use of the data generated by this clinical study will be in 
compliance with the terms specified in the Clinical Research Agreement. 
A Publication Plan and Policy will be developed based on the guiding principles of the 
International Committee of Medical Journal Editors (ICMJE) Guidelines. 
 
A ‘Publication Agreement’ will be signed between the Principal Investigator and the 
Sponsor either as a separate Publication Agreement or within the Clinical Trial 
Agreement. 
 
For more information on publication guidelines, please refer to the International 
Committee of Medical Journal Editors (ICMJE) on www.icmje.org. 
 
 
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 40 of 41 
 
11.0 
References: 
 
1. Rodriguez-Roisin R. Toward a Consensus Definition for COPD Exacerbations. Chest. 2000;117: 398s-
401s.  
 
2. Huynh TT, Liesching TN, Cereda M, Lei Y, Frazer MJ, Nahouraii MR, Diette GB. Efficacy of Oscillation 
and Lung Expansion in Reducing Postoperative Pulmonary Complications. J Am Coll Surg. 2019 
Nov;229(5): 458-466. 
 
3. Patel P, Fukushima L, Balekian A, Chou W, Lu A, Gali V, et al. Is MetaNeb comparable to high frequency 
chest compression in the setting of a severe pulmonary exacerbation in adults with cystic fibrosis?  
Pediatr Pulmonol 2013;48(Suppl 36):359. 
 
4. Hsieh J, Prickett M, Willis N, DeCamp M, de Hoyos A. A comparison of positive pressure modalities in a 
respiratory therapist driven protocol for patients post anatomic lung resection. Respir Care. 
2014;59(10):2017931. 
 
5. Morgan S, Hornik CP, Patel N, Williford WL, Turner DA, Cheifetz IM. Continuous high-frequency 
oscillation therapy in invasively ventilated pediatric subjects in the critical care setting. Respir Care. 
2016 Nov 1; 61(11): 1451-5. 
 
6. Sharma R, Prickett M, Coleman JM, Hixon J, Wolfe LF. Adherence to therapy and patient reported 
satisfaction using a novel airway clearance and lung expansion treatment in motor neuron disease 
(MND) and cystic fibrosis (CF) patients in the home setting [abstract]. Am J Respir Crit Care Med. 
2018;197:A6271. 
 
 
 
 
 
 
 

 
 
 
 
 
PROTOCOL TITLE 
Evaluation of Oscillation and Lung Expansion (OLE) using The Volara® System for treatment of 
respiratory complications in patients with neuromuscular disease in the home setting 
Final Protocol  
Protocol Number: CR-RR-2020-005 
Date:      11May2022 
 
 
 
Page 41 of 41 
 
 
 
12.0 
 List of Abbreviations 
 
ADE 
Adverse Device Effect 
BMI 
Body Mass Index 
CHFO 
Continuous High Frequency Oscillation 
CPEP 
Continuous Positive Expiratory Pressure 
EC 
Ethics Committee 
ED 
Emergency Department 
GCP 
Good Clinical Practice 
IRB 
Institutional Review Board 
IV 
Intravenous 
MIP 
Maximal Inspiratory Pressure 
NMD 
Neuromuscular Disease 
OLE 
Oscillation and Lung Expansion 
PCF 
Peak Cough Flow 
QOL 
Quality of Life 
SpO2 
Oxygen Saturation – obtained by pulse oximetry 
SVC 
Slow Vital Capacity 
VC 
Vital Capacity