The Effect of Preoperative and Postoperative Incentive Spirometry in Patients Undergoing Major Abdominal Surgery
Phase: NA
Conditions: Abdominal Surgery
Sponsor: Washington University School of Medicine

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The effect of preoperative and postoperative incentive spirometry  
in patients undergoing major abdominal surgery 
 
 
Washington University School of Medicine 
Department of Surgery 
660 South Euclid Avenue, Campus Box 8109 
St. Louis, MO  63110 
 
Protocol #: 202105028 
Version Date: 06 April 2022 
 
Principal Investigator: 
Chet Hammill, M.D., MCR 
Phone:  (314) 273-1809 
E-mail:  hammillc@wustl.edu 
 
 
Sub-Investigators 
 
 
 
 
Modality 
Dominic Sanford, MD, MPH  
 
 
Hepatobiliary Surgery 
William Hawkins, MD, FACS 
 
 
Hepatobiliary Surgery 
Steven Strasberg, MD, FACS  
 
 
Hepatobiliary Surgery 
Ryan Fields, MD, FACS 
 
 
 
Hepatobiliary Surgery 
Jorge Zarate Rodriguez, MD  
 
 
Hepatobiliary Surgery 
Esther Lu, MS, PhD  
 
 
 
Biostatistics 
Gregory Williams, M.A. 
 
 
 
Surgery 
 
 
 
Study Device(s): 
 
MIR Spirobank G  
ZephyrX  
 
NCT#: 
NCT04887922 
Funded by: 
Big Ideas Grant (Institute for Informatics) 
 
 
CONFIDENTIAL 
The information contained in this document is regarded as confidential and, except to the extent necessary to 
obtain informed consent, may not be disclosed to another party unless law or regulations require such 
disclosure.  Persons to whom the information is disclosed must be informed that the information is 
confidential and may not be further disclosed by them. 
 

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The effect of preoperative and postoperative incentive spirometry  
in patients undergoing major abdominal surgery 
 
 
Protocol Revision History 
 
Initial Approval Version 
 
 
 
 
 
 
30 April 2021 
Amendment #1 Version 
 
 
 
 
 
 
06 April 2022  
 
 
 

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STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 
 
 
 
 
 
 

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Table of Contents 
 
PROTOCOL SUMMARY ..........................................................................................................5 
Synopsis ..................................................................................................................................5 
SCHEMA ...................................................................................................................................7 
SCHEDULE OF ACTIVITIES ...................................................................................................8 
1.0 
INTRODUCTION ............................................................................................................9 
1.1 
Background/Rationale ...................................................................................................9 
1.2 
Study Design............................................................................................................... 10 
2.0 
OBJECTIVES AND ENDPOINTS ................................................................................. 10 
3.0 
STUDY POPULATION ................................................................................................. 11 
3.1 
Inclusion Criteria ........................................................................................................ 11 
4. 
Ability to understand and willingness to sign an IRB approved written informed 
consent document. ............................................................................................................. 12 
3.2 
Inclusion of Women and Minorities ............................................................................ 12 
4.0 
REGISTRATION PROCEDURES ................................................................................. 12 
4.1 
Confirmation of Patient Eligibility .............................................................................. 12 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database........................... 12 
4.3 
Assignment of UPN .................................................................................................... 12 
4.4 
Screen Failures............................................................................................................ 12 
5.0 
STUDY PROCEDURES ................................................................................................ 13 
5.1 
Definitions of Evaluability .......................................................................................... 14 
6.0 
REGULATORY AND REPORTING REQUIREMENTS .............................................. 14 
6.1.1 
Reporting to the Human Research Protection Office (HRPO) at Washington 
University.......................................................................................................................... 14 
6.1.2 
Reporting to the Quality Assurance and Safety Monitoring Committee (QASMC) 
at Washington University .................................................................................................. 14 
7.0 
DATA SUBMISSION SCHEDULE ............................................................................... 15 
8.0 
DATA AND SAFETY MONITORING .......................................................................... 15 
9.0 
STATISTICAL CONSIDERATIONS ............................................................................ 16 
9.1 
Study Design............................................................................................................... 16 
9.2 
Randomization ............................................................................................................ 16 
9.3 
Data Collection ........................................................................................................... 16 
9.4 
Endpoints .................................................................................................................... 17 
9.5 
Sample Size/Power Analysis ....................................................................................... 17 
9.6 
Data Analysis .............................................................................................................. 17 
10.0 REFERENCES ............................................................................................................... 18 
 
 
 
 

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PROTOCOL SUMMARY 
 
Synopsis 
 
Title: 
The effect of preoperative and postoperative incentive spirometry 
(IS) in patients undergoing major abdominal surgery 
Study Description: 
The goal of this study is to determine the efficacy of incentive 
spirometry (IS) to improve pulmonary function in the preoperative 
and postoperative surgical setting. We hypothesize that IS will 
improve pulmonary function for patients undergoing major 
abdominal surgery when controlling for protocol compliance. 
Additionally, we hypothesize that a digital IS device enabled with a 
text message-based mobile health intervention will improve 
pulmonary 
pre-habilitation 
and 
rehabilitation, 
as 
well 
as 
postoperative compliance with the IS device. 
Objectives: 
Primary Objective: 
To determine the efficacy of incentive spirometry to improve FEV1 
in the preoperative surgical setting.  
 
Secondary Objectives: 
1. To determine the efficacy of incentive spirometry to improve 
FVC and pulse oximetry in the preoperative surgical setting.  
2. To determine the change in FEV1, FVC and pulse oximetry 
after surgery. 
 
Exploratory Objectives: 
1. To determine the daily number of times patients perform 
incentive spirometry in the preoperative and postoperative 
setting. 
2. To determine whether standard incentive spirometers move 
throughout a patients’ postoperative stay using accelerometers, 
as a proxy for how often patient uses the device. 
3. To evaluate whether a digital IS device + text message based 
mobile health intervention will improve FEV1, FVC, and pulse 
oximetry compared to standard IS. 
4. To evaluate the rate of pulmonary complications across the 3 
preoperative groups. 
Endpoints: 
Primary Endpoint: 
Change in FEV1 at day-of-surgery preoperative from baseline 
 
Secondary Endpoints: 
1. Change in FVC and pulse oximetry at day-of-surgery 
preoperative from baseline 
2. Change in FEV1, FVC and pulse oximetry at postoperative day 
3 from day 1 
 

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Exploratory Endpoints: 
1. Daily frequency of digital IS use. 
2. Movement data of standard IS with accelerometers (this is a 
proxy endpoint for IS use). 
3. Difference in changes in FEV1, FVC, and pulse oximetry 
between randomized groups. 
4. Postoperative complications defined by Modified Accordion 
Grading System (MAGS) 
Study Population: 
We plan to enroll 156 adult patients who are scheduled to undergo 
major abdominal surgery with an expected postoperative hospital 
stay of > 48 hours. 
Phase: 
N/A 
Description of Sites / 
Facilities Enrolling: 
The 
study 
will 
take 
place 
at 
Barnes 
Jewish 
Hospital 
system/Washington University School of Medicine. 
Description 
of 
Study 
Intervention: 
Patients will be randomized into 3 groups: (1) control group with no 
IS, (2) standard IS, and (3) digital IS + text message. Groups 2 and 3 
will be instructed to perform spirometry every day for at least 7 days 
prior to surgery. FEV1, FVC, and pulse oximetry will be obtained 
for all patients at 4 different time points: (1) baseline measurement 
at the time of enrollment, (2) preoperatively on the day of surgery, 
(3) immediate postoperative period 24 hours after surgery, and (4) 
delayed postoperative period on postoperative day 3. After surgery, 
patients are re-randomized to conventional spirometry (which is 
standard of care) or digital spirometry. The digital spirometer 
couples with a HIPAA-compliant mobile app which stores data and 
shares it with the research team via the HIPAA-compliant dashboard. 
These data will be used to assess compliance with the intervention 
for the digital group both in the preoperative and postoperative 
period. Sustained accelerometer movement data will be used as a 
surrogate for frequency of use and will be used to assess compliance 
with the intervention for the standard group in the postoperative 
period. 
Study Duration: 
 Approximately 1000 major abdominal surgeries take place at our 
institution yearly. The rate-limiting step for enrollment is going to be 
the digital IS devices, which we plan to re-use. Purchasing 20-30 
devices for 150 patients, we anticipate completing accrual in 12 
months. (Note that all patients receive an individualized spirometry 
mouthpiece; only the digital device that does not come into contact 
with patient is re-used.) We anticipate data analysis will be 
completed 6 months following closure to accrual. 
Participant Duration: 
Approximately 1 month 
 
 
 
 
 
 
 
 
 
 

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SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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SCHEDULE OF ACTIVITIES 
 
 
 
Baseline/Enrollment Pre-
operative 
Days 1-7 
Day of 
surgery 
Post-
operative 
Day 1 
Post-
operative 
Day 3 
Consent1 
X 
 
 
 
 
Randomization2 
X 
 
 
 
 
Re-
randomization3 
 
 
 
X 
 
Spirometry 
intervention 
 
X5 
 
X 
X 
FEV1, FVC, pulse 
oximetry 
X 
 
X4 
X 
X 
Assess for 
AE/Complications 
X 
X 
X 
X 
X 
Notes: 
1. Consent should take place not less than 8 days prior to surgery. 
2. Patients will be randomized into three groups: (1) control group with no IS, (2) standard 
IS, and (3) digital IS + text message. 
3. Following surgery, patients will be re-randomized into two groups: (1) standard IS, and 
(2) digital IS + text message. 
4. Measurement of PFTs and pulse oximetry should be obtained prior to surgery on the day 
of surgery. 
5. For groups 2 and 3 only. 
 
 
 

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1.0 
INTRODUCTION 
 
1.1 
Background/Rationale 
Recent developments in perioperative care, like the development of enhanced recovery 
pathways, have been designed to decrease practice variability and achieve early recovery 
after surgery to decrease the postoperative length of hospitalization for patients.1-5 Despite 
this, there has not been a significant reduction in postoperative readmissions.6-8 The 
complication rate after major abdominal surgery such as pancreaticoduodenectomy and 
liver resection continues to be up to 50%.8-10 Most research aiming to improve 
postoperative outcomes has focused on postoperative interventions, but in the last couple 
of years, there has been significant interest in developing interventions that address the 
preoperative period.11-18 One specific intervention that has been proposed with limited and 
variant support is the use of incentive spirometry (IS). IS involves using a device to 
facilitate deep breathing exercises to increase lung capacity and open airways with the goal 
to prevent pulmonary complications.19-23  
 
IS has had widespread implementation in the United States in the postoperative period 
although there is limited data supporting its efficacy in clinical trials. A systematic review 
by Overend et al. evaluated 46 studies to ascertain the effect of postoperative IS on the 
incidence of postoperative complications, but failed to show a positive effect for 
postoperative IS.24 More recently, Zoremba et al. evaluated the effect of IS in the 
postoperative recovery unit on lung function for obese patients undergoing a variety of 
non-abdominal surgical procedures.25 They did not find significant differences in pulse 
oximetry and pulmonary function tests (PFTs) immediately after surgery, but at all 
subsequent time points—1, 2, 6, and 24 hrs after surgery—SpO2, FVC, FEV1 and PEF 
were higher for the IS group. In summary, data regarding postoperative IS use is sparse 
and inconsistent. 
 
There is emerging field of study to evaluating IS in the preoperative setting which have 
yielded mixed results.23,26,27 A 2010 study from Kundra et al. evaluated the effect of 
preoperative IS on patients undergoing laparoscopic cholecystectomy and failed to show 
any differences in preoperative PFTs compared to baseline in the control group, while 
patients in the intervention group had a 11.9% increase in FEV1 and 12.1% increase in 
FVC compared to baseline.28 Additionally, Fulop et al evaluated the use of IS 4-5 times 
daily before undergoing colorectal surgery in which the intervention group had improved 
inspiratory capacity compared to baseline, compared to the control group in which the 
inspiratory capacity remained the same (113% vs 100% of baseline value).29 Similarly, a 
group from India reported their results of preoperative IS regiment consisting of 15 mins 
of IS every 4 hrs for 7 days before surgery, compared to standard of care.30 Preoperative 
control peak expiratory flow rate (PEFR) was not different between groups, and 
postoperatively they only found a statistically significant difference on postoperative day 

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2 (69.48% intervention vs 61.66% control of baseline PEFR). In all the preoperative studies 
there was no statistically significant differences in postoperative morbidity and mortality. 
 
In summary, there is a significant knowledge gap and methodological concerns regarding 
the benefits of IS use across the continuum of surgical care. As reported above, there is a 
substantial variance in IS specific measurements and outcomes evaluated across many 
surgical studies in the preoperative and postoperative period. An important, and 
unaddressed, methodological issue with the current data available is the lack (and 
unreported) data pertaining to the compliance of patients using the IS as intended.23  Most 
protocols reported in the literature detail the patient IS instructions/protocol ranging from 
IS use at 4-5 times per a day up to 10 times per hour but fail to objectively evaluate and 
adjust their analyses to patients successful completing the IS protocol. 31-33 
 
To overcome the methodological problems recent technologies have emerged that can 
accurately track IS use and could be used to address this limitation. ZEPHYRx® has 
developed a 1) digital Bluetooth-enabled IS that allows for the continuous and objective 
remote monitoring of patient compliance with pre- and postoperative IS via a smartphone 
app and online provider dashboard. New research has suggested that mobile health based 
interventions can be used successfully to change patient behavior. If coupled with 
ZEPHYRx® technology, these could be used to increase patient compliance with IS.34-38 
They have also developed 2) accelerometer implanted standard IS devices; which 
utilizes an accelerometer to monitor movement of the IS device as a proxy for IS use using 
standard non-Bluetooth enabled IS devices.  
 
1.2 
Study Design 
The goal of this study is to determine the efficacy of IS to improve pulmonary function in 
the preoperative and postoperative surgical setting. We hypothesize that IS will improve 
pulmonary function for patients undergoing major abdominal surgery when controlling for 
protocol compliance. Additionally, we hypothesize that a digital IS device + text message 
based mobile health intervention will improve pulmonary pre-habilitation and 
rehabilitation, as well as postoperative compliance with the IS device.  
 
 
2.0 
OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Justification for 
Endpoints 
Primary 
To determine the efficacy of 
incentive spirometry to 
improve FEV1 in the 
preoperative surgical setting.  
Change in FEV1 at day-of-
surgery 
preoperative 
from 
baseline 
 
 

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Secondary 
3. To determine the efficacy 
of incentive spirometry to 
improve FVC and pulse 
oximetry in the 
preoperative surgical 
setting.  
4. To determine the change in 
FEV1, FVC and pulse 
oximetry after surgery. 
 
1. Change in FVC and pulse 
oximetry at day-of-surgery 
preoperative from baseline 
2. Change in FEV1, FVC and 
pulse 
oximetry 
at 
postoperative day 3 from day 
1 
 
 
Tertiary/Exploratory 
1. To determine the number 
of times patients perform 
incentive spirometry in the 
preoperative and 
postoperative setting. 
2. To determine whether 
standard incentive 
spirometers move 
throughout a patients’ 
postoperative stay using 
accelerometers, as a proxy 
for how often patient uses 
the device.. 
3. To evaluate whether a 
digital IS device + text 
message based mobile 
health intervention will 
improve FEV1, FVC, and 
pulse oximetry compared 
to standard IS. 
4. To evaluate the rate of 
pulmonary complications 
across all 6 groups. 
1. Daily frequency of IS use 
2. Postoperative complications 
defined by Modified 
Accordion Grading System 
(MAGS) 
 
 
 
3.0 
STUDY POPULATION 
 
3.1 
Inclusion Criteria 
 
1. Patients scheduled to undergo major abdominal surgery with expected postoperative 
length of stay of 48 hours or more. 
 
2. Access to a smartphone. 

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3. At least 18 years of age. 
4. Ability to understand and willingness to sign an IRB approved written informed 
consent document. 
 
3.2 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this trial.   
 
 
4.0 
REGISTRATION PROCEDURES 
 
Patients must not start any protocol intervention prior to registration through the Siteman 
Cancer Center. 
 
The following steps must be taken before registering patients to this study: 
 
1. Confirmation of patient eligibility  
2. Registration of patient in the Siteman Cancer Center database 
3. Assignment of unique patient number (UPN) 
 
4.1 
Confirmation of Patient Eligibility 
 
Confirm patient eligibility by collecting the information listed  
1. The registering MD’s name 
2. Patient’s race, sex, and DOB 
3. Three letters (or two letters and a dash) for the patient’s initials 
4. Copy of signed consent form  
5. Completed eligibility checklist, signed and dated by a member of the study team 
6. Copy of appropriate source documentation confirming patient eligibility 
 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database 
 
All patients must be registered through the Siteman Cancer Center OnCore database. 
 
4.3 
Assignment of UPN 
 
Each patient will be identified with a unique patient number (UPN) for this study.  All data 
will be recorded with this identification number on the appropriate CRFs. 
 
4.4 
Screen Failures 
 
Screen failures are defined as participants who consent to participate in the clinical trial 
but are not subsequently randomized to the study intervention or entered in the study.  A 
minimal set of screen failure information is required to ensure transparent reporting of 
screen failure participants, to meet the Consolidated Standards of Reporting Trials 

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(CONSORT) publishing requirements and to respond to queries from regulatory 
authorities.  Minimal information includes demography, screen failure details, eligibility 
criteria, and any serious adverse event (if applicable).   
 
 
5.0 
STUDY PROCEDURES 
 
After enrolling in the study, patients will be randomized pre-operatively into one of the 
following 3 groups: (1) control group with no IS, (2) standard IS, and (3) digital IS + text 
message (see schema). Baseline PFTs and pulse oximetry on room air will be obtained for 
all patients. 
 
Patients in the control group will not receive a spirometer for preoperative use, which is 
current standard of care. Patients in the standard group will receive a conventional 
spirometer; they will receive instruction on how to perform spirometry correctly and will 
be asked to perform spirometry 30 times a day, as per the Washington University Surgical 
Prehabilitation and Readiness Program (SPAR) protocol. Patients in the digital group will 
receive an FDA-approved, Bluetooth digital spirometer (Spirobank G) that is compatible 
with health monitoring software developed by ZEPHYRx®. All patients receive an 
individual mouthpiece in which to breathe. The digital devices that are separate from but 
attached to the mouthpiece may be re-used. These will be thoroughly cleaned between 
patients. The digital spirometer couples with a HIPAA-compliant mobile application that 
calculates and stores PFT results. The research team will have access to the data via the 
ZEPHYRx® provider dashboard. Patients in the digital spirometer group will receive the 
same instruction as the patients in the standard IS group and asked to follow the same 
preoperative IS protocol. Absence of spirometry for 24 hours will trigger a text message 
reminder to encourage compliance with IS.   
 
On the day of surgery, PFTs and pulse oximetry on room air will be recorded for all patients 
in the preoperative area. After surgery, all patients will receive a spirometer as is standard 
of care. On postoperative day 1, patients will be re-randomized. Those in the standard 
group will receive a standard spirometer for postoperative use, whereas patients in the 
digital group will obtain a digital spirometer (Spirobank G + ZEPHYRx®-enabled). All 
patients will receive instruction on how to perform spirometry and will be instructed to 
perform spirometry 10 times per hour, every hour while awake as is current practice for 
the department of surgery. The conventional spirometer will be equipped with an 
accelerometer that will allow the research team to determine whether the spirometer moves 
throughout the patients’ postoperative stay (as a proxy for IS use) in the standard group. 
Compliance amongst the digital group will be determined using the ZEPHYRx® 
dashboard as described above.  Just as in the preoperative period, the digital group will 
receive text reminders to perform spirometry if they do not perform spirometry in a 24-

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hour period. PFTs and pulse oximetry on room air will be obtained on postoperative day 1 
and postoperative day 3. The clinical inpatient team will be blinded to compliance data. 
 
After obtaining final measurements on postoperative day 3, the study will conclude, and 
the spirometers will be collected. Postoperative outcomes data, including perioperative 
mortality postoperative complications, length of stay, and need for readmission, will be 
collected for all patients as per protocol for the Division of Hepatobiliary Surgery. 
 
5.1 
Definitions of Evaluability 
 
All patients who are initially randomized are evaluable for the primary endpoint.  Patients 
are evaluated from first enrollment through post-operative day 3. 
 
 
6.0 
REGULATORY AND REPORTING REQUIREMENTS 
 
The entities providing oversight of safety and compliance with the protocol require reporting as 
outlined below.   
 
Adverse events will be tracked from start of spirometry intervention through post-operative day 3. 
All adverse events must be recorded on the toxicity tracking case report form (CRF) with the 
exception of: 
• Baseline adverse events, which shall be recorded on the medical history CRF 
• Any adverse events related to presenting diagnosis or surgery 
• Any adverse events determined unrelated to spirometry 
 
6.1.1 Reporting to the Human Research Protection Office (HRPO) at 
Washington University 
 
Reporting will be conducted in accordance with Washington University IRB 
Policies. 
 
Pre-approval of all protocol exceptions must be obtained prior to implementing the 
change. 
 
6.1.2 Reporting to the Quality Assurance and Safety Monitoring 
Committee (QASMC) at Washington University 
 
The PI (or designee) is required to notify the QASMC of any unanticipated 
problems involving risks to participants or others occurring at WU or any BJH or 
SLCH institution that has been reported to and acknowledged by HRPO.  
(Unanticipated problems reported to HRPO and withdrawn during the review 
process need not be reported to QASMC.) 
 

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QASMC must be notified within 10 days of receipt of IRB acknowledgment via 
email to qasmc@wustl.edu.  Submission to QASMC must include the myIRB form 
and any supporting documentation sent with the form. 
 
 
7.0 
DATA SUBMISSION SCHEDULE 
 
Case report forms with appropriate source documentation will be completed according to the 
schedule listed in this section. 
 
Case Report Form 
Submission Schedule 
Original Consent Form 
Prior to registration 
On-Study Form 
Medical History Form 
At enrollment/baseline 
PFT + pulse oximetry 
Baseline, preoperatively on day of surgery, post-op day 
1, post-op day 3 
Surgery form 
Day of surgery (+1 week) 
Follow-up Form 
1 month post-op 
AE log 
Continuous 
 
 
8.0 
DATA AND SAFETY MONITORING 
 
In compliance with the Washington University Institutional Data and Safety Monitoring Plan, the 
Principal Investigator will provide a Data and Safety Monitoring (DSM) report to the Washington 
University Quality Assurance and Safety Monitoring Committee (QASMC) semi-annually 
beginning six months after accrual has opened (if at least one patient has been enrolled) or one 
year after accrual has opened (if no patients have been enrolled at the six-month mark). 
 
The Principal Investigator will review all patient data at least every six months, and provide a 
semi-annual report to the QASMC. This report will include: 
• HRPO protocol number, protocol title, Principal Investigator name, data coordinator 
name, regulatory coordinator name, and statistician 
• Date of initial HRPO approval, date of most recent consent HRPO approval/revision, 
date of HRPO expiration, date of most recent QA audit, study status, and phase of study 
• History of study including summary of substantive amendments; summary of accrual 
suspensions including start/stop dates and reason; and summary of protocol exceptions, 
error, or breach of confidentiality including start/stop dates and reason 
• Study-wide target accrual and study-wide actual accrual 
• Protocol activation date 
• Average rate of accrual observed in year 1, year 2, and subsequent years 
• Expected accrual end date  
• Objectives of protocol with supporting data and list the number of participants who 
have met each objective 
• Measures of efficacy 

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• Early stopping rules with supporting data and list the number of participants who have 
met the early stopping rules 
• Summary of toxicities  
• Abstract submissions/publications 
• Summary of any recent literature that may affect the safety or ethics of the study  
 
The study principal investigator and Research Patient Coordinator will monitor for serious 
toxicities on an ongoing basis. Once the principal investigator or Research Patient Coordinator 
becomes aware of an adverse event, the AE will be reported to the HRPO and QASMC according 
to institutional guidelines. 
 
 
9.0 
STATISTICAL CONSIDERATIONS 
 
9.1 
Study Design 
 
This is a prospective, single-center, randomized trial. The enrolled patients will be 
randomized 1:1:1 to one of three groups: control, standard IS, and digital IS + text message. 
They will have baseline measurement at the time of randomization, and pre-operative 
measurement after randomization and before the surgery. After surgery, patients will be 
re-randomized to either standard IS or digital IS + text message. Measurements at post-op 
days 1 and 3 will be taken. The primary objective of this study is to determine the efficacy 
of incentive spirometry to improve FEV1 in the preoperative setting.  The secondary 
objectives are to determine the efficacy of incentive spirometry to improve FVC and pulse 
oximetry in the preoperative setting, and FEV1, FVC, and pulse oximetry in the 
postoperative setting. The exploratory objectives are to determine the daily number of 
times patients perform incentive spirometry in the postoperative setting and evaluate the 
rate of pulmonary complications across the 3 preoperative groups. 
 
9.2 
Randomization 
 
A computer-generated randomization scheme with various block sizes will be used to 
assign patients. It is maintained centrally by the study statistician.  After enrollment in the 
study and obtaining consent, randomization will take place in REDCap. 
 
9.3 
Data Collection 
 
FEV1, FVC, and pulse oximetry will be obtained for all patients at 4 different time points: 
(1) baseline measurement at the time of enrollment; (2) preoperatively on the day of 
surgery; (3) immediate postoperative period 24 hrs after surgery; and (4) delayed 
postoperative period on postoperative day 3. The digital spirometer couples with a HIPAA-
compliant mobile app which stores data and shares it with the research team via a HIPAA-
compliant dashboard. These data will be used to assess compliance with the intervention 
for the digital group both in the preoperative and postoperative period. Sustained 
accelerometer movement data will be used as a surrogate for frequency of use and will be 

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used to assess compliance with the intervention for the standard group in the postoperative 
period. 
 
9.4 
Endpoints 
 
The primary endpoint is FEV1 change at day-of-surgery preoperative from baseline. The 
secondary endpoints include FVC and pulse oximetry change at day-of-surgery 
preoperative from baseline, change in FEV1, FVC and pulse oximetry at preoperative day 
3 from day 1. Exploratory Endpoints are daily frequency of IS use and postoperative 
complications defined my Modified Accordion Grading System (MAGS).39  
 
9.5 
Sample Size/Power Analysis 
 
The sample size calculation is based on the primary outcome only. Previous research has 
shown that the mean difference in FEV1 between control and preoperative incentive 
spirometry intervention groups  is 0.4 L with a standard deviation of 0.6.28 Bonferroni 
correction will be used for three-group comparisons. Sample sizes of 49 per group achieve 
80.6% power to detect the difference in FEV1 assuming a mean difference of 0.4 L and a 
standard deviation of 0.6 at a significance level of 0.017 using a two-sided, two-sample, 
equal-variance t-test. To account for a 5% dropout rate, we will enroll 52 patients per group 
for a total of 156 patients enrolled in the study.  
 
9.6 
Data Analysis  
 
The analysis will be intent-to-treat approach. The FEV1, FVC and pulse oximetry changes 
at day-of-surgery preoperative from baseline will be compared across three groups using 
ANOVA or Kruskal-Wallis test, as appropriate. The linear regression model will be 
considered to adjust for the other interested variables including age, sex, smoking status, 
BMI, ASA, and malignancy. The same analysis method will be conducted for  FEV1, FVC 
and pulse oximetry changes at preoperative day 3 from day 1. The frequency of use, defined 
as the daily number of times patients perform incentive spirometry, will be compared 
across all groups in the postoperative setting using ANOVA or Kruskal-Wallis test, as 
appropriate. For postoperative complications, Chi-square test will be used to test the 
differences between six groups. The univariate logistic regression model will estimate the 
odds ratio of postoperative complication. Multivariate analysis through stepwise selection 
will be considered to examine the relationship between binary outcome and independent 
predictors, where a significance level of 0.3 is required to allow a predictor into the model, 
and a significance level of 0.35 is required for a predictor to stay in the model. All analyses 
will be conducted using SAS (SAS Institute, Cary, NC) at the two-sided 5% significance 
level.  
 
 

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We would like to thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine 
and Barnes-Jewish Hospital in St. Louis, Missouri, for the use of the Clinical Trials Core which provided 
protocol development services. The Siteman Cancer Center is supported in part by an NCI Cancer Center 
Support Grant #P30 CA91842.