Feasibility Study of a Mask Adhesive in Patients Treated With NIV in an Institutional Setting
Phase: NA
Conditions: Respiratory Failure, Covid19
Sponsor: Philips Clinical & Medical Affairs Global

Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol 
Classification: 
Confidential 
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors 
 BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
1 of 30 
Clinical Protocol 
Feasibility Study of a Mask Adhesive in Patients Treated with NIV in an Institutional 
Setting  
Version 2.0 
FINAL 
Protocol ID: SRC_HRC_Mask Adhesive (MANIV Trial)_2020_11130 
21 APR 2020 
Amendment 1 
Sponsored By 
Philips RS North America LLC f/k/a Respironics, Inc. 
6501 Living Place 
Pittsburgh, PA 15206 
Sponsor Approval 
Author Signature 
Date 
Author Signature 
Date 
Author Signature 
Date 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
3 of 30 
 
Table of Contents 
 
Table of Contents ........................................................................................................................ 3 
Document Control Page(s) ......................................................................................................... 4 
Sponsor Contact Information .................................................................................................... 5 
1. 
PROTOCOL SYNOPSIS ....................................................................................................... 6 
2. 
Background Information ..................................................................................................... 8 
3. 
Description of the Study Product ....................................................................................... 9 
4. 
Study Purpose ................................................................................................................... 10 
5. 
Study Objectives and Endpoints ...................................................................................... 10 
6. 
Study Design and Rationale ............................................................................................. 11 
7. 
Study Population ............................................................................................................... 11 
8. 
Study Procedures .............................................................................................................. 12 
9. 
Statistical Methods ............................................................................................................ 17 
10. 
Direct Access to Source Data/Documents .................................................................. 19 
11. 
Adverse Events Handling and Reporting .................................................................... 21 
12. 
Device Deficiencies ........................................................................................................ 23 
14. 
Quality Control and Quality Assurance ....................................................................... 24 
15. 
Ethics .............................................................................................................................. 25 
16. 
Data Handling and Recordkeeping ............................................................................... 25 
17. 
Benefit/Risk Assessment .............................................................................................. 25 
18. 
Product Accountability .................................................................................................. 26 
19. 
Registration on ClinicalTrials.gov or Other Applicable Registry .............................. 26 
20. 
Publication ...................................................................................................................... 27 
 
 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
4 of 30 
 
Document Control Page(s) 
 
Protocol Title:  Feasibility Study of a Mask Adhesive in Patients Treated with NIV in an 
Institutional Setting 
Protocol ID:  SRC_HRC_Mask Adhesive (MANIV Trial)_2020_11130 
 
Protocol Version: 2.0 
 
Version Date: 21 APR 2021 
 
Author(s): Beth Galaska, MID; Jeff Jasko, MS; Melissa Weiner, MPH 
 
Study Sponsor: 
 
Respironics California, LLC 
Hospital Respiratory Care   
2271 Cosmos Ct  
Carlsbad, CA 92011 
 
 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
5 of 30 
 
Sponsor Contact Information 
 
Sponsor Contact Information 
 
Study Monitor: 
 
Melissa Weiner  
Clinical Research Associate  
  
  
 
 
Reporting of Adverse Events or Adverse Device Effects 
 
Report the occurrence of a serious adverse events, serious adverse device effects, or 
unanticipated adverse device effects to Philips within 24 hours of the occurrence. 
 
 
Melissa Weiner  
Clinical Research Associate  
  
  
 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
6 of 30 
 
1. PROTOCOL SYNOPSIS 
 
 
Title: 
Feasibility Study of a Mask Adhesive in Patients Treated with NIV in 
an Institutional Setting 
Study Design: 
Randomized, Open-Label, Crossover Study  
Objectives: 
Primary Objectives:   
• 
To determine the incidence of severe medical adhesive-
related skin injury (MARSI) when used in an institutional 
setting 
• 
To evaluate the mask adhesive ease-of-use in an institutional 
setting 
 
Secondary Objective:  
• 
To evaluate the performance of the mask adhesive in 
reducing leaks in an institutional setting   
Endpoints: 
Primary Endpoints:   
• 
Proportion of patients who have severe and extreme skin 
irritation that persists for ≥ 30 min after mask adhesive 
removal (score of ≥ 3 on a 5-point grading system)  
• 
Clinician-perceived mask adhesive ease-of-use as measured 
by a 0-10 Likert Scale (initial impressions/end of study) 
Secondary Endpoint:  
• 
Leak reduction. Calculated percentage change in 
unintentional leak volume (L/min) after mask adhesive use as 
compared to the use of the mask without the adhesive 
Study Population: 
• 
Up to 30 adult patients treated with NIV will be enrolled in this 
study 
• 
Up to 30 clinicians at each site who treat patients during this 
study 
Description the 
Accessory to be 
tested: 
The Philips mask adhesive is an optional accessory to the AF531 or 
PerformaTrak masks.  It is a double-sided adhesive, with one side 
applied directly to the patient’s skin and the other side connected to 
the mask cushion. The adhesive is only to be applied to a patient 
once. The mask cushion side can be removed from the adhesive 
and then re-applied, as necessary. For example, if the patient needs 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
7 of 30 
 
to remove the mask to eat or take medicine, the mask is removed 
from the patient and the adhesive will stay on the patient’s face.    
Study Duration: 
 Estimated 9 month accrual and follow-up period.  
Participant 
Duration: 
Participant study duration will be a maximum of 5 business days, 
with 2 nights of planned intervention and ~8 hours of adhesive mask 
use. 
 
 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
8 of 30 
 
2. Background Information 
 
Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the novel 
coronavirus (nCoV) which has spread rapidly around the world.1  
 
Approximately 14% people with COVID-19 develop severe disease that requires 
hospitalization and oxygen support, and 5% require intensive care and can be complicated 
by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.2  It has 
been reported that 19% of the patients with COVID -19 experience hypoxic respiratory 
failure3  requiring  ventilatory support such as high-ﬂow nasal oxygen (HFNO), invasive and 
noninvasive ventilation (NIV).  
 
NIV refers to the delivery of positive pressure ventilation through an interface such as nasal 
mask, face mask, or a helmet and it is recommended as a treatment for patients with mild-
to-moderate acute respiratory failure.4  
 
Although effectiveness on improving survival NIV has been supported by several 
randomized trials,5 there is a concern with the use  NIV in patients with respiratory tract 
infection due to the potential respirable aerosol (droplet size < 5 µm) and larger droplet (> 10 
µm) spread as the mode of transmissible infections.6,7 It is recognized that unintentional 
leaks and poor fitting of the NIV interface8 increase the risk of spreading droplets that might 
carry contaminating viruses, increasing the risk of spreading the disease to other patients 
and  health care workers.9  
 
To reduce interface leak and aerosol spread, Philips has developed an accessory to non-
invasive ventilation masks to be used with the Philips AF531 and the PerformaTrak mask. 
For the purposes of capturing initial mask leak and safety data, this study will enroll patients 
treated with NIV in an institutional setting (i.e., sleep lab).  
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
9 of 30 
 
3. Description of the Study Product  
 
The Mask Adhesive serves as an accessory to the AF531/PerformaTrak masks with the 
intent to reduce patient leak while a patient is receiving therapy. This accessory is a double-
sided adhesive; with one side applied directly to the patient’s skin and the other side 
connected to the mask cushion. Each adhesive is only to be applied to a patient once. The 
AF531/Performatrak mask can be removed from the adhesive and then re-applied, as 
necessary. For example, if the patient needs to remove the mask to eat or take medicine, 
the mask is removed from the patient and the adhesive will stay on the patient’s face. The 
instructions for use (IFU) state that the adhesive should be replaced as necessary by the 
caregiver. The material used in the adhesive mask is an acrylic tape, 3MTM Medical Foam 
Tape 1774T (3M Health Care, St Paul, Minnesota) and it has undergone safety evaluations 
including in vitro cytototoxicity, MEM Elution, Primary Skin Irritation and Sensitization. All 
tests were conducted in compliance with the requirements of ISO 10993-5: Biological 
Evaluation of Medical Devices, Part 5: Tests for In Vitro Cytotoxicity and ISO 10993-10, 
Biological Evaluation of Medical Devices, Part 10: Tests for Irritation and Delayed-Type 
Hypersensitivity.   
 
Intended Use: The adhesive accessory is intended to secure the mask cushion to the 
patient’s face. The adhesive accessory is for single patient use in the hospital/institutional 
environment only.   
 
Contraindications: Adhesive is not to be used on patients with a pre-existing allergy to tape 
or adhesive, existing skin breakdown or wounds, or skin that lacks the integrity to support 
removal of adhesive without tearing. 
 
Warnings  
• Monitor the patient during use of the adhesive and suspend use if the patient is 
showing any signs of skin breakdown 
• Do not apply over current blisters, open skin or pre-existing skin conditions 
• The Mask Adhesive is not a replacement for the headgear. Always use the headgear 
with the mask and Mask Adhesive 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
11 of 30 
 
6. Study Design and Rationale 
 
This is a randomized, open-label, crossover study to assess the ease-of-use and performance 
of a Class I medical device accessory.  Participants (patients and clinicians) will undergo the 
informed consent process and sign an informed consent form (ICF).  This study will be 
completed according to ICH for Good Clinical Practice guidance E6 (R2) Good Clinical Practice, 
March 2018 and the Declaration of Helsinki.  The study will be monitored in accordance with the 
Study Monitoring Plan. 
 
7. Study Population 
 
7.1 Patients 
 
Up to 30 patients will be enrolled over an estimated nine month accrual and follow-up evaluation 
period.   
Inclusion Criteria 
• 
Adults aged 18 to 85 (inclusive) 
• 
Adults treated with NIV  
• 
Able to read, write, and speak English 
• 
Able to provide written informed consent 
• 
Willing to have facial hair removed for adhesive placement (if required) 
 
Exclusion Criteria 
• 
Pre-existing allergy to tape or adhesive  
• 
Blisters, open skin or pre-existing skin condition that may impact the ability to support 
removal of the mask adhesive without tearing the skin 
• 
Pregnant (for females of childbearing age)  
• 
Individuals sentenced to such an institution under a criminal or civil statute, individuals 
detained in other facilities by virtue of statutes or commitment procedures which 
provide alternatives to criminal prosecution or incarceration in a penal institution, and 
individuals detained pending arraignment, trial, or sentencing 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
12 of 30 
 
Withdrawal 
 
The term “discontinuation” refers to the participant’s premature withdrawal from the study prior 
to completing all procedures.  Participants may be discontinued from the study for any of the 
following reasons: 
• 
If in the Investigator’s judgment, continuation in the study may prove harmful to the 
participant.  Such a decision may be precipitated by adverse events, including fever, 
nausea, rash, changes in vital signs, or the development of a new medical condition.  
The Investigator will be solely responsible for making medical/safety decisions regarding 
the participant’s continued participation in the study. 
• 
If the mask is found to be inadequate for use (i.e., seal stability, comfort, air flow) 
• 
At the request of the participant. 
• 
At the request of the Study Sponsor, Philips. 
 
The study team will document whether each participant completed the study.  Successful study 
completion will be defined as the placement and removal of at least one mask adhesive.  If, for 
any participant, study treatment or assessments were discontinued, the reason will be recorded. 
Participants may withdraw from the study at any time.  Withdrawal from the study will not affect 
their medical treatment or future participation in a research study.  Participants that withdraw 
from the study will not be replaced, and no further data will be collected after date of withdrawal.  
 
8. Study Procedures 
 
Participants’ safety  
The FDA Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 
Public Health Emergency will be followed and local procedures will be followed to ensure the 
safety of study participants, maintain compliance with good clinical practice (GCP), and 
minimize risks to study integrity for the duration of the COVID-19 public health emergency.   

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
13 of 30 
 
8.1 Patients 
 
Pre-Screening 
Potential participants will be pre-screened predominantly through chart review from the existing 
site databases of patients. All efforts will be made to ensure patient privacy. The study staff will 
provide verbal explanation regarding the nature of the study via telephone screening.  In 
addition, IRB-approved recruitment materials will be posted and available for distribution at the 
clinic. 
 
Screening and Enrollment 
The study will be explained to the patients by qualified site personnel.  The patient will be given 
time to read the consent document and ask any questions that they might have. Individuals who 
agree to participate will be asked to sign the consent form. Eligibility will be assessed following 
informed consent.  If the participant is found to be ineligible, all study procedures will stop and 
the participants will be considered a screen fail.   
 
Baseline Data Collection   
After the patient provides informed consent and eligibility has been assessed, the following 
patient information will be reviewed and collected via participant self-report: 
• 
Demographics including, e.g. age, race, ethnicity, gender, etc. 
• 
Anthropometric data, e.g., height and weight, etc. 
• 
Relevant medical history, current NIV therapy (i.e., settings, mask, duration of 
BiPAP use, etc.) including any known allergies to acrylic tape or adhesive 
• 
Concurrent medications 
• 
Baseline facial skin assessment to evaluate skin breakdown or wounds, or skin that 
lacks the integrity to support removal of adhesive without tearing, dental 
assessment, etc.  
 
Randomization.  Participants will be randomly allocated to the order of mask use. Participants 
allocated to study arm 1 will use the mask with the mask adhesive on the first study night and 
the mask only on the second study night. Participants allocated to study arm 2 will use the mask 
only on the first study night, and the mask with the mask adhesive on the second study night.  

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
15 of 30 
 
o Device Settings and leak 
• 
Mask information: AF531 or PerformaTrak, and mask size  
 
Facial Skin Assessment: 
• 
A 5-point MARSI grading scale will be used to evaluate erythema/edema.  The 
scale will be as follows: 
o 0=No redness  
o 1=Slight redness, barely perceptible 
o 2=Definite redness  
o 3=Severe redness (well defined) with edema 
o 4=Extreme response with edema (swelling) 
 
Mask adhesive placement Before the night when the mask adhesive will be used, clinicians 
will follow the instructions for use and the product identification number will be recorded.  
 
After mask application and initiation of the BiPAP therapy, the following parameters will 
be recorded after patient stabilization: 
• 
Mask information: AF531 or PerformaTrak, mask size  
• 
Vent Settings/Information (personal or site provided with standard of care therapy):  
o Device brand name, model 
o Time/Date of NIV initiation 
o Settings and leak 
• 
SpO2 levels  
• 
EtCO2 (when available) 
 
Overnight Procedure 
The participants will be monitored continuously during the night by a trained sleep technologist, 
including standard of care measures, ECG, SPO2, etc.   
Leak, O2 levels and EtCO2 (when available) will be recorded. 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
18 of 30 
 
confidence interval, effect size, and number of observations.  Categorical data will be presented 
as frequencies, percentages and 95% Clopper-Pearson confidence intervals. Any formal 
significance testing will be performed at p < 0.05.  There are no statistical criteria for terminating 
the study and any deviations from the original statistical plan will be noted in the analysis report. 
 
Primary Analysis 
Incidence of Severe Medical Adhesive-Related Skin Injury 
Patients who have severe and extreme skin irritation that persists for ≥ 30 min after mask 
adhesive removal (score of ≥ 3 on the 5-point grading system) will be summarized by 
percentage and frequency of occurrence. The results will also be presented with a 95% 
Clopper-Pearson confidence interval. 
 
Mask Adhesive Ease-of-Use  
The clinician-reported ease-of-use ratings will be inspected for normality.  Depending on the 
distributions of the data, a paired t-test or Wilcoxon Signed-Ranks test will examine whether the 
average (or median) score is greater than 5.  This will be tested both on the initial-impression 
and end-of-study ratings, with Sidak adjustment to account for multiple comparisons.  In 
addition, a paired t-test or Wilcoxon Signed-Ranks test will examine whether there is a 
significant change in ratings between these two intervals [end of study] – [initial impression]. 
 
Secondary Analysis 
Leak Reduction 
Percentage change in leak will be calculated as ([Leak with the mask adhesive applied] – [Leak 
without the mask adhesive])/[Leak without the mask adhesive].  The percentage change will be 
examined using either a paired t-test or the nonparametric Wilcoxon Signed-Ranks test, 
depending on the distribution of the data.  Sub-group analysis will be performed to explore the 
impact of differing dental conditions.  
 
Exploratory Analysis 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
19 of 30 
 
Mask Adhesive Participant Comfort 
The participant-reported comfort ratings will be inspected for normality.  Depending on the 
distributions of the data, a paired t-test or Wilcoxon Signed-Ranks test will examine whether the 
average (or median) score is greater than 5. 
 
Factors Associated with the Development of MARSI and Patient Leak Data Captured Over 
Time 
If adequate data are collected, an exploratory analysis may be performed.  The details of this 
analysis would be described in the study report. 
 
Participant Disposition 
Participant disposition, including the total number of participants enrolled, completed, early 
terminations and withdrawals, will be presented. A listing will be provided with the reasons for 
discontinuation. 
 
Subject Accountability and Missing Data 
Participants who withdraw from the study will be tabulated with the reasons for the withdrawal.  
It is not anticipated that imputation methods will be required. 
 
Safety Analysis 
All reportable adverse events (serious and non-serious) that occur during the study will be 
documented on the Adverse Event form or eCRF, and the data will be provided in listings.   
 
Interim Analysis 
No interim analysis is planned. 
 
10. Direct Access to Source Data/Documents 
 
As part of the study, the study team will record information that contains the participants’ name 
and other personal identifiers.  Study records that identify participants will be kept confidential, 
as required by law.  Federal Privacy Regulations require us to safeguard participant information 
including implementing privacy and security safeguards to prevent unauthorized access to 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
20 of 30 
 
records.  Except when required by law, name, social security number, address, telephone 
number, or any other direct personal identifiers in study records disclosed outside of the 
research site will not identify participants.  Records of participants will be assigned a unique 
code number. The key to the code will be kept separately, will be secured and is only made 
available to specific study staff. 
 
Results of the study related data and information obtained from the questionnaires will be 
reported to Philips.  Philips will use participant study data for research purposes to support the 
scientific objectives described in this document.  In addition, participant records may be 
reviewed in order to meet federal and state regulations.  Reviewers may include representatives 
from the FDA or similar government authorities in other countries where the device is being 
used, and Philips for the purposes of following side effects and gathering additional information 
related to the study.  If a participant’s research record is reviewed by any of these groups, 
information used and disclosed may include the entire research record and clinical and research 
observations made during participation in the research study.  Participant permission for review 
of confidential information is granted by signing the associated consent form.  Philips will ensure 
that it follows all applicable state and federal data protection regulations. 
 
The study results will be retained for two years; however, the coded data will be retained 
indefinitely.  The Sponsor will use and disclose participant study information only for research or 
regulatory purposes or to prepare research publications or presentations at meetings. 
 
Clinical study records will be maintained in a site study binder and will be stored in locked 
cabinets under the control of the Principal Investigator.  Electronic data collected will be stored 
in an access controlled secured database indefinitely. No patient identifying information will be 
stored in the electronic data capture and no patient identifying information will be used in any 
reports, meeting presentations, or publications of this study. 
 
The data collected during this study may be reanalyzed at a later date and may be combined 
with the results of other studies. Philips and those approved by Philips may use the results of 
this study for other research purposes, including: 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
21 of 30 
 
1. Reviewing the safety or effectiveness of the study device and other products or 
therapies; 
2. Evaluating other products or therapies for patients; 
3. Developing a better understanding of disease 
 
A protocol deviation is any noncompliance with the clinical study protocol. Noncompliance may 
be either on the part of the participant, the Investigator, or the study site staff. As a result of 
deviations, corrective actions are to be developed by the site and implemented promptly. 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within five working days of identification of the protocol deviation, or within five 
working days of the scheduled protocol-required activity.  All deviations must be addressed in 
study source documents and reported to the Sponsor. All deviations are to be documented on 
the provided protocol deviation log. 
   
11. Adverse Events Handling and Reporting  
 
This study is a preliminary feasibility study of a cleared medical device accessory.  
Unanticipated and anticipated adverse events will be recorded if they are definitely, probably, or 
possibly related to the investigational device as determined by principal Investigator or 
designee.  All events captured will be reported to the Sponsor by the research staff; however, all 
SAEs, SADEs, UADEs must be reported to the Sponsor within 24 hours of discovering the 
occurrence of the SAE.  The research staff is required to complete and submit the Sponsor’s 
standard SAE form detailing the event. AE’s and SAE’s will be reported to the IRB per their 
policy.  
 
Relationship to Study Intervention 
All adverse events (AEs) must have their relationship to study intervention initially assessed by 
the clinician or designee.  The Principal Investigator (PI) will examine and confirm the temporal 
relationship based on his/her clinical judgment. The degree of certainty about causality will be 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
22 of 30 
 
graded using the categories below. In a clinical study, the device under investigation must 
always be suspect.  
• 
Definitely Related – An AE is definitely related to study participation if it is clear that the 
event was caused by study participation. A definitely related event has a strong temporal 
relationship and an alternative cause is unlikely. 
• 
Probably Related – An AE is probably related when there is a reasonable possibility that 
the event is likely to have been caused by study participation. The AE has a timely 
relationship to the study procedure(s) and follows a known pattern of response, but a 
potential alternative cause may be present. 
• 
Possibly Related – An AE is possibly related when there is a reasonable possibility that 
the event might have been caused by study participation. A possibly related event may 
follow no known pattern of response and an alternative cause seems more likely. In 
other circumstances there may be significant uncertainty about the cause of the event, 
or a possible relationship to study participation cannot reasonably be ruled out. 
• 
Unrelated/Not Related – The cause of the AE is known and the event is in no way 
related to any aspect of study participation. If there is any uncertainty regarding AE 
causality then the event must be assessed as possibly related to research participation 
and reported to the IRB as indicated. Often, the cause of an unrelated AE is disease 
progression 
 
An adverse event or device deficiency that does not meet the definition of reportable does not 
require reporting to the Sponsor (or the eCRFs), unless the approving IRB/EC, regulatory 
authority requires reporting.  An Investigator may opt to report any safety event that does not 
meet any of the above if thought to be clinically relevant to product use.  All reportable AEs 
deemed to be related study product will be followed clinically until the AE resolves (returns to 
baseline) or stabilizes.  
 
The disposition of all safety events, assignment of relatedness, and seriousness is the 
responsibility of the Principal Investigator.   
 
All reportable adverse events will be reported in an interim or final report of the clinical study. 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
23 of 30 
 
Expedited Reporting 
Any SAE, SADE, UADE and will be reported to the Sponsor within 24 hours of the study staff 
learning of the event:   
 
Melissa Weiner  
Clinical Research Associate  
  
  
Promptly thereafter, the study staff will provide a detailed written report that includes at 
minimum, the requirements for issuing a complaint.  Additionally, upon Philips’ request, the 
Investigator will provide further information related to the safety reporting of a particular event.   
 
The Sponsor will report any unanticipated adverse device effect (regardless of seriousness) to 
the IRB within 5 days of becoming aware of the event.  Additionally, the Sponsor, in conjunction 
with the service location and Investigator, will report to regulatory authorities as required by 
national regulations.   
 
12. Device Deficiencies 
 
Device deficiencies, use or user errors, and equipment failures will be documented.  Use or 
User errors will be captured as part of the source documentation.  Device deficiencies and 
equipment failures will be kept on a separate log.  The serial numbers and type of 
deficiency/failure will be captured. Unanticipated device deficiencies that lead or may lead to an 
SAE will be reported to the Sponsor within 24 hours of learning of the event. 
 
13. 
Case Report Forms 
 
Study data will be collected on paper or electronically.  Case report forms will include 
information regarding participant eligibility, performed study procedures, protocol deviations, 
device deficiencies, and AEs.  Data collection is the responsibility of the clinical trial staff. The 
clinical trial staff is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported.  Only those staff that have been delegated by the PI will be able 
to enter or make changes to the data in the case report forms 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
24 of 30 
 
14. Quality Control and Quality Assurance 
 
Training 
The PI and study personnel will be trained to the study protocol, study product, TMF documents, 
monitoring plan, CRFs and/or eCRFs, direct data reporting (see associated task), and all 
Sponsor expectations, as applicable. Once complete, training and delegations will be 
documented for PI and study personnel. 
 
Monitoring and Monitoring Plan 
Remote monitoring visits will be performed periodically and will be conducted by trained clinical 
research professionals. The monitoring process includes initial site qualifications, site initiations 
visit, monitoring visits, contact with site staff, and a close-out visit. Study monitoring will be 
conducted in accordance with the study monitoring plan.  
 
Data Management System  
Datatrak 
As specified in the Data Management Plan, all data will be entered into DataTrak, a 21 CFR 
Part 11-compliant data capture system provided by the Sponsor. The data will be housed within 
a secure server (based in Virginia, USA) and accessible only to the Sponsor, study personnel, 
and investigators.  Access to the Electronic Data Capture (EDC) system will be secured through 
login/password control managed by a system administrator and appropriated training will be 
provided. The EDC system provides the capability to perform data management activities within 
a consistent, auditable, and integrated electronic environment (data security, data entry, data 
validation). Data entries and modifications will be recorded via an audit trail. If the data manager 
or study monitors identify data errors or inconsistencies, they will generate queries that will be 
sent to the Principal Investigators and study staff. After queries are resolved, the database will 
be locked, and the data will be imported into a statistical software and analyzed by 
biostatisticians. 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
25 of 30 
 
15. Ethics 
 
The study and any subject facing materials will be reviewed by an Institutional Review Board 
(IRB) and the study will not begin until approval has been received by the IRB.  
 
Privacy rules and requirements according to governing regulations will be implemented. All the 
information collected as part of this study will be kept confidential. All information collected for 
this study will be kept in a secured area or stored in a password protected computer if digital. 
Except when required by law, participants will not be identified by name, social security number, 
address, telephone number, or any other direct personal identifier in study records. For records 
disclosed outside Sponsor, participants will be assigned a unique code number.  The key to the 
code will be kept by the Investigator. Data will be managed by study number and analyzed 
anonymously. 
A unique source record will be available for each study participant including documentation of 
the informed consent form review process, HIPAA completion to ensure patient privacy (United 
States), if applicable, medical history, and concomitant medications review. 
 
16. Data Handling and Recordkeeping  
 
The site study binder will be kept on site for at least 2 years after study completion.  The 
Sponsor will maintain the Trial Master File as defined by Philips retention policies. Records will 
be stored a secure information management services company. 
 
17. Benefit/Risk Assessment 
 
Reducing the leak from the mask will potentially lead to the following benefits. 
1) 
The adhesive may reduce leak thereby reducing the amount of air leaking from the 
patient into the room and that will help to reduce the risk of transmission of COVID-19 
and other transmittable disease. The reduction in the risk of transmission of COVID-19 
may also reduce the fear of the healthcare providers. This may increase the time they 
can spend with patients.  

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
26 of 30 
 
2) 
The Adhesive may reduce the probability of overtightening the headgear and that 
will reduce the probability of pressure sores that occur over time. 
3) 
The availability of a mask with minimal leak might encourage earlier extubation (to 
noninvasive ventilation) and thus reduce length of intubation. 
 
The addition of the adhesive accessory has raised the initial probability of harm for Skin 
abrasion due to removal of adhesive.  The following control measures have been 
implemented: 
• 
Design control measure –The design and application will limit the removal of the 
adhesive to the patient to one time. When the mask is removed from the patient the 
cushion will be removed from the adhesive and the adhesive will remain on the 
patient. This will limit the number of times the adhesive is applied and removed from 
the patient’s skin. 
• 
Labeling control measure –Contraindication – Adhesive is not to be used on patients 
with a pre-existing allergy to tape or adhesive, existing skin breakdown, wounds and 
skin that lacks the integrity to support removal of adhesive without tearing. 
• 
Labeling control measure –Warning – Monitor the patient during use of the adhesive 
and suspend use if the patient is showing any signs of skin breakdown. 
• 
COVID-19 is a risk with any in-person activity, but safety precautions, such as 
screening, disinfection of study materials, and other site safety measures, will be 
taken to minimize your risk. 
The benefit/risk analysis (ER 2239807) conducted as part of the risk management process 
concludes that based on the risk mitigations in place, the probability of potential harm is 
reasonably low and the benefits of the new accessory outweighs the potential risk. 
 
18. Product Accountability 
Sites will document lot/batch number upon receipt.  
 
19. Registration on ClinicalTrials.gov or Other Applicable Registry  
This trial will be registered on ClinicalTrials.gov as this clinical study is intended for publication 
in a scientific journal. 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
27 of 30 
 
 
20. Publication  
Study data and results may be used/considered for submission to a peer-reviewed publication, 
white paper or scientific abstract. 
 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
28 of 30 
 
References  
 
1. 
WHO. Clinical management of severe acute respiratory infection when Novel 
coronavirus (nCoV) infection is suspected: interim guidance. 2020. 
2. 
Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with 
SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, 
observational study. The Lancet Respiratory medicine. 2020;8(5):475-481. 
3. 
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus 
Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases 
From the Chinese Center for Disease Control and Prevention. JAMA. 
2020;323(13):1239-1242. 
4. 
Rochwerg B, Brochard L, Elliott MW, et al. Official ERS/ATS clinical practice guidelines: 
noninvasive ventilation for acute respiratory failure. The European respiratory journal. 
2017;50(2). 
5. 
Cabrini L, Landoni G, Oriani A, et al. Noninvasive ventilation and survival in acute care 
settings: a comprehensive systematic review and metaanalysis of randomized controlled 
trials. Critical care medicine. 2015;43(4):880-888. 
6. 
Tellier R, Li Y, Cowling BJ, Tang JW. Recognition of aerosol transmission of infectious 
agents: a commentary. BMC infectious diseases. 2019;19(1):101. 
7. 
Cabrini L, Landoni G, Zangrillo A. Minimise nosocomial spread of 2019-nCoV when 
treating acute respiratory failure. Lancet (London, England). 2020;395(10225):685. 
8. 
Murthy S, Gomersall CD, Fowler RA. Care for Critically Ill Patients With COVID-19. 
JAMA. 2020;323(15):1499-1500. 
9. 
Otero DP, Domínguez DV, Fernández LH, et al. Preventing facial pressure ulcers in 
patients under non-invasive mechanical ventilation: a randomised control trial. Journal of 
wound care. 2017;26(3):128-136. 
 
 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
29 of 30 
 
Appendices 
Appendix 1: Instructions for Use (IFU) 
Appendix 2: Ease of Use Questionnaire for Clinicians 
Appendix 3: Participant Trial Survey 
 

 
Document 
ID: 
SRC_HRC_Mask Adhesive 
(MANIV Trial)_2020_11130 
Clinical Protocol  
Classification: 
Confidential  
Feasibility Study of a Mask Adhesive in Patients Treated with 
NIV in an Institutional Setting 
Modified: 
21APR2021 
Authors   BG, JJ, MW 
Version: 
2.0 
User Tool ID: 
16.2.6UserTool0003 
Approver 
See above 
Status: 
Final 
User Tool Version Date: 8Jul2019 
Page: 
30 of 30 
 
Document Revision History 
Version 
Date 
Authors 
Description of Change 
Reason for Change 
1.0 
2 NOV 2020 
FSK, BG, JJ 
N/A 
N/A 
2.0 
21 APR 2021 
BG, JJ, MW 
Study personnel update, 
extension of the duration of 
accrual, clarification to 
participants’ duration of trial 
participation update to the 
possible collection of 
photographs for skin 
evaluation, registration on 
clinicaltrials.gov and 
submission to peer-
reviewed publications, 
administrative changes. 
Full Version Amendment.