Active Clearance of Chest Tubes After Cardiac Surgery: A Prospective Randomized Controlled Study
Phase: NA
Conditions: Atrial Fibrillation, Pericardial Effusion, Pleural Effusion, Hemothorax, Cardiac Tamponade
Sponsor: Montreal Heart Institute

Clinical Trial Protocol 
 
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Rev. 4, Febuary 2016 
Active Clearance Technology® Improves Post Operative 
Atrial Fibrillation- The ACT POAF Trial 
 
Study Protocol #: MP-33-2015-1901 
 
 
 
 
Clinical Study Support: 
ClearFlow, Inc. 
1630 S. Sunkist St., Suite E 
Anaheim, CA 92806 
USA 
 
 
 
 
 
 
 

Clinical Trial Protocol 
 
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Rev. 4, Febuary 2016 
 
 
 
Active Clearance Technology® Post Operative Atrial 
Fibrillation Trial - The ACT POAF Trial  
 
1. 
ADMINISTRATIVE INFORMATION AND KEY ROLES: 
1.1 
Protocol Title: Active Clearance Technology® Improves 
Post-Operative Atrial Fibrillation - The ACT POAF Trial 
1.2 
Coordinating Principle Investigator: Dr Philippe Demers 
1.3 
Clinical Study Support: 
Clinical Study Support has 
been provided by ClearFlow, Inc 1630 South Sunkist St., 
Suite E, Anaheim California, 92806, USA 
 
 
1.4 
Monitor: Trained monitors will conduct periodic site 
monitoring visits.  Purpose of the visits is to verify that data 
entered to the study database matches the source data.  
Monitors will coordinate visits with the site personnel  
 

Clinical Trial Protocol 
 
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Rev. 4, Febuary 2016 
 
 
 
2. 
SYNOPSIS 
2.1 
Protocol Title: 
Active Clearance Technology® Improves 
Post Operative Atrial Fibrillation- The ACT POAF Trial 
2.2 
Protocol Number: MP-33-2015-1901 
2.3 
Sponsor: 
ClearFlow, Inc. has provided partial support for 
this trial 
2.4 
Objectives: 
1. To assess the effectiveness of the PleuraFlow® Active 
Clearance Technology® (ACT) in reducing the rate of 
postoperative atrial fibrillation (POAF) among post cardiac 
surgery patients 
 
2. To evaluate the impact of ACT on retained blood syndrome 
(RBS) and other complications after cardiac surgery. 

Clinical Trial Protocol 
 
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2.5 
Study Design: 
This is a prospective, randomized, single blinded  two-arms, 
single-center Post Market Clinical Follow-Up (PMCF) Study. The 
test arm consists of consecutively enrolled cardiac surgery 
patients receiving < two (2) PleuraFlow® chest tubes with 
Active Clearance Technology® and < two (2) other 
commercially available chest tubes. The 1 control arms consist 
of consecutively enrolled cardiac surgery patients receiving < 
four (4) commercially available standard chest tubes. In all 
arms, one (1) chest tube must be placed in the anterior 
mediastinum. The other chest tube(s) may be placed at the 
discretion of the operator. Chest tubes with internal diameter 
28 FR to 32 FR shall be used.  
2.6 
 Study Population: 
-Up to 508 evaluable post-cardiac surgery female and male 
subjects, 18 years of age and older will be consecutively 
enrolled in the study. 
- Subjects are required to meet all inclusion criteria and none of 
the exclusion criteria to be included in this PMCF study.  
Subjects must be informed about this study and a written and 
signed informed consent must be obtained from the subject 
prior to cardiac surgery. 
2.7 
Number of Subjects/sites: 
Up to 508 evaluable subjects enrolled at the Montreal Heart 
Institute and Sacré-Coeur of Montreal Hospital 
2.8 
Gender/Age:  
 
Females and males, 18 years of age and older. 
 
 
2.9 
Inclusion Criteria:  
Subjects will be required to meet all Inclusion Criteria:  
1. Admission for CABG, valve replacement or valve repair 
surgery, or a combination of these surgeries; 
2. Surgical procedure(s) on the ascending aorta and/or aortic 
arch that do not require deep hypothermic arrest (deep 
hypothermic arrest is defined as < 14° C); 
3. Must be in sinus rhythm (SR) for a minimum of 30 days 
prior to the index surgery and at the start of the index 
surgery. No patient with history of atrial fibrillation. 
4. Sign the IRB/IEC approved informed consent form after the 
nature of the study has been explained and 
questions/concern have been addressed. 
 

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2.10 
                    Exclusion Criteria: 
 
Subjects will be required to meet none of the exclusion criteria: 
1. Admitted for surgical treatment of arrhythmia or Atrial 
fibrillation history; 
2. Admitted for cardiac surgery requiring 
implantation/explantation of a Ventricular Assist Device 
(VAD) or heart transplant; 
3. Admitted for Transcatheter aortic valve replacement (TAVR); 
4. Cardiac surgical procedure that requires deep hypothermic 
arrest (as defined above); 
5. New or active endocarditis or myocarditis that is not 
adequately controlled with medication and/or requires 
surgical intervention; 
6. Documented inherited bleeding disorder(s); 
7. History or known allergies to the device materials; or 
8. Participation in another clinical investigation.  If a subject 
has recently completed participation in another drug or 
device clinical investigation, the subject must have 
completed that study at least thirty (30) days prior to being 
enrolled in this clinical study. 
2.11 
Device: 
 
 
 
ClearFlow’s PleuraFlow® Catheter System 
2.12 
                               Indications for Use: 
The PleuraFlow® ACT® System is indicated for use as an 
adjunctive device during open surgical procedures in order to 
prevent fluid accumulation within the operative site after 
closure of the surgical wound. The device is indicated for use in 
cardiothoracic surgical procedures. 
2.13                          Endpoints: 
2.13.1 Primary performance endpoint 
• 
Rate of any episode of new onset of Post-Operative Atrial 
Fibrillation (POAF) in the study group. POAF is defined as 
any atrial fibrillation episode ≥ 60 min on telemetry or 
EKG. At any time between post index surgery through 
hospital discharge. 
 
 
 
 
 
 

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2.13.2 Secondary performance endpoints 
•  Rate of interventions to treat Retained Blood Syndrome 
(RBS). RBS is a composite endpoint defined as an 
intervention to treat one or more of the following 
conditions: 
-Re-exploration for bleeding, tamponade or washout of 
retained blood [Time Frame: discharge from OR to 30 
days post index surgery]; 
-Any procedure to treat Pericardial effusion; i.e., 
pericardial window, pericardiocentesis, placement of 
pericardial drain [Time Frame: discharge from OR to 30 
days post index surgery]; 
-Any procedure to treat Pleural effusion; i.e., 
thoracentesis under any image-guided modality [Time 
Frame: discharge from OR to 30 days post index 
surgery]; 
-Any procedure to treat hemothorax (i.e., chest tube, 
thoracoscopy, thoracotomy, etc.) [Time Frame: 
discharge from OR to 30 days post index surgery]Any 
procedure to treat Pneumothorax. [Time Frame: 
discharge from OR to 30 days post index surgery]. 
• 
Readmission for any diagnosis of RBS and/or POAF-
related occurrences [Time Frame: within 30 days post 
index surgery].  
• 
Readmission for any reason.  [Time Frame: within 30 
days post index surgery]. 
 
 
2.13.3 Other Outcomes:  
• 
Mortality [Time Frame: within 30 days post index 
surgery]; 
 
Length of Hospital Stay [Time Frame: day of discharge]; 
 
Stay in the Intensive Care Unit (ICU) [Time Frame: 
hours];  
 
Ventilation time [Time Frame: hours to extubation]; 
 
Transfusion postoperative [Time Frame: total number 
and type of units used]; 
 
Total chest tube output first 24 hours [Units: milliliters]; 
 
Total chest tube drainage [Units: milliliters]; 

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Any cardiac arrest [Time Frame: within 30 days post 
index surgery]; 
 
Stroke [Time Frame: within 30 days post index 
surgery]; 
 
Renal failure requiring dialysis [Time Frame: within 30 
days post index surgery]; 
 
Renal insufficiency with serum creatinine level 3 times 
greater than baseline level or serum creat level > 300 
µmol/L. [Time Frame: within 30 days post index 
surgery]; converter en umol/L pour nous. 
 
Surgical Site Infection:  
 
-Sternal Superficial Wound Infection: (i) within 30 days 
post index surgery; (ii) 30 days post index surgery but 
during hospitalization; (will be confirmed at postoperative 
surgeon appointment) 
 
-Deep Sternal Infection/Mediastinitis; within 30 days 
post index surgery (will be confirmed at postoperative 
surgeon appointment) 
 
-Post-op Pneumonia; within 30 days post index surgery 
(will be confirmed at postoperative surgeon appointment) 
 
Septicemia [Time Frame: hospital discharge]; 
 
Sepsis [Time Frame: within 30 days post index surgery]; 
 
Urinary tract infection [Time Frame: within 30 days post 
index surgery]; 
2.14                            Data Management:  
Data will be collected and stored at the department of surgery 
of Montreal Heart Institute. Only the princiapal investigator 
and study coordinators will have access to the database. 
 
 
2.15                              Statistics 
 
Sample Size Calculations: 
 
The primary analysis will be an intention-to-treat (ITT) 
analysis comparing the POAF rate in the PleuraFlow® group to 
the POAF rate in the control group. Based on findings from our 
institutional clinical database at the Montreal Heart Institute, 
the 
local 
incidence 
of 
POAF 
after 
cardiac 
surgery 
is 
approximately 25% (control group). The proportion in group 
Pleuraflow (the treatment group) is assumed to be 0,2500 
under the null hypothesis and 0,1500 under the alternative 
hypothesis. Group sample sizes of 254 in each group achieve 
80% power to detect a difference between the group 

Clinical Trial Protocol 
 
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Rev. 4, Febuary 2016 
 
 
proportions of 0,1000 using a Chi-Square test with a 
significance level of 0.0476. This significance level is computed 
using the O’Brien-Fleming method and accounts for the   
interim analysis that is planned after 300 randomized subjects 
have completed their 30-day follow-up.  
 
Statistical Analysis 
POAF and intervention to treat RBS rates and all other 
categorical event rates will be compared using chi-square 
tests. Multiple logistic regressions to adjust for potential 
confounding factors will also be used. Odds ratio and 
associated 95% confidence intervals will be computed for 
descriptive purpose. Goodness of fit will be checked using 
Hosmer-Lemeshow statistics. Quantitative endpoints will be 
investigated using Student t-tests. Analysis of covariance may 
also be used to account for potential confounding factors. 
Nonparametric tests or data transformation may be used if 
quantitative 
endpoints 
are 
not 
normally 
distributed. 
Correlations and associated 95% confidence intervals will be 
computed for descriptive purpose. 
An interim analysis will be conducted on the first 300 
randomized subjects completing their 30-day follow-up. The 
primary endpoint (POAF rate) will be compared between the 
PleuraFlow® group and the control group using a chi-square 
test. The significance level for this test will be 0.0076, as 
computed using the O’Brien-Fleming method. If the p-value of 
the chi-square test is below this bound at the interim analysis, 
the study will be stopped for efficacy. Otherwise, the study will 
continue up to the planned 508 patients. As a result of this 
interim look, the final analysis of the primary endpoint would 
require a p < 0.0476 to be declared statistically significant. 
Analysis of the secondary endpoints and other outcomes will 
be conducted at the 0.05 significance level. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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3 
Abbreviations and Definitions 
 
Table 1 Abbreviations and Explanations 
Term
Definition
ACT
Active Clearance Technology
AFib 
Atrial Fibrillation 
CABG 
Coronary Artery Bypass Graft 
CFR 
US code of Federal Regulations 
CRF 
Case Report Form 
CRO
Contract Research Organization
CVA 
Cerebrovascular Accident 
IEC 
Independent Ethics Committee 
FDA 
Food and Drug Administration 
GCP 
Good Clincial Practice 
HIPAA
Health Insurance Portability and Accountability Act
ICF 
Informed Consent Form 
ICU 
Intensive Care Unit 
IFU 
Instructions for Use 
NIS 
US National Inpatient Sample 
IRB
Institutional Review Board
ITT 
Intent to Treat 
MDR 
Mandatory Medical Device Reporting (US) 
MI 
Myocardial Infarction 
PCI 
Percutaneous Coronary Intervention 
PF-CA 
PleuraFlow Clearance Apparatus 
PF-CT
PleuraFlow Chest Tube
PMCF 
Post Market Clinical Follow-up Study 
PHI 
Personal Health Information 
POAF 
Postoperative Atrial Fibrillation 
PP 
Per Protocol 
RBS
Retained Blood Syndrome
SAE 
Serious Adverse Event 
UADE 
Unanticipated Adverse Device Effect 
VAD 
Ventricular Assist Device 
VTE 
Venous Thromboembolism 
WBC
White Blood Count
WMA
World Medical Association

 
 
 
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4 
Background and Rationale 
 
Post Operative Atrial Fibrillation (POAF) is one of the most common complications after 
heart surgery, occurring in 20% to 60% of patients, and is a leading cause of hospital 
costs and readmissions.[1] Based on findings from our institutional clinical database at 
the Montreal Heart Institute, the local incidence after cardiac surgery is approximately 
25%. In the NIH POAF study, the Montreal Heart Institute result’s show an incidence of 
35% of POAF (33/95 recruted patient). POAF is associated with an increased risk of 
mortality and morbidity, predisposes patients to a higher risk of stroke, requires 
additional treatment, and increases the costs of the post-operative care.[2]  There are 
currently no reliable preventative approaches that can be uniformly applied to all 
patients in a prophalactic fashion to reduce this complication.  Various drug regimins 
have been tested, but must be selectively applied and can have undesirable side 
effects.[3]  The development of a universally applicable prophalactic approach that 
reduces POAF broadly would be a great advance for cardiac surgery patients.  
 
Although the etiologiy of POAF is likely multifactorial, recent evidence suggest that 
inflammation around the heart during recovery may play a role in the development of 
POAF.[4, 5]  Unevacuated retained blood is a common finding, which has been 
postulated as driving an inflammatory response around the heart during early 
recovery.[2, 6]  Retained blood occurs when shed blood is incompletely evacuated from 
around the heart after surgery.  When patients bleed in the early hours after heart 
surgery, reliable postoperative blood evacuation of the pleural, mediastinal and 
pericardial spaces with chest tubes is imperative to facilitate pulmonary reexpansion 
and mediastinal decompression as the patient recovers. When blood encounters the 
artificial surfaces of chest tubes, the coagulation cascade is initiated, which often leads 
to partial or complete chest tube obstruction. In a recent study of postoperative cardiac 
surgery patients at the Cleveland Clinic, 36% of patients were found to have evidence 
of chest tube obstruction.[7] Chest tube clogging can lead to inadequate evacuation of 
shed blood in the mediastinal or pleural spaces, termed Retained Blood Syndrome 
(RBS).[6]  RBS is the presence of postoperative pericardial and/or pleural blood that is 
diagnosed and may necessitate drainage of bloody effusions in the acute or subacute 
setting. Patients with occluded chest tubes have been shown to have a higher rate of 
POAF, suggesting a link between occluded chest tubes, the development of RBS and 
POAF.[7]   
 
Clinical studies reinforce this link by demonstrating that more complete postoperative 
drainage of the pericardium reduces the incidence of POAF.[8, 9]  In a prospective 
study, Ege and colleagues demonstrated a reduction in POAF from 23.8% to 11.3% by 
employing a redundant multi-drainage tube strategy to reduce retained blood.[10] In a 
similar study, Eryilmaz and colleagues reduced the incidence of POAF from 32.7% to 
10.4% with a protocol aimed at minimizing retained pericardial blood early after 
operation.[10] In all of these studies, there appears to be a link between bloody 
pericardial effusions and development of POAF.  While the precise mechanism behind 
this effect is unclear, reduced inflammation from minimizing retained blood and clot in 
the pericardium may be contributory.[8, 9]   
 
Chest tube clogging has long been a concern in early post operative recovery.[11]  
Methods such as chest tube stripping or milking, or opening chest tubes to remove clots 
with balloon catheters have been utilized but have been shown to be ineffective and 
possibly even harmful, leading to a significant unmet need on how to best maintain 
chest tube patency after surgery.[12-14]  Preventing chest tube occlusion to facilitate 

 
 
 
12 
Rev. 4, Febuary 2016 
 
maximal drainage of blood around the heart in the early hours of recovery after cardiac 
surgery has the potential to alleviate this problem.  The PleuraFlow® System with Active 
Clearance Technology® (ClearFlow Inc. Anaheim, CA), was developed by surgeons to 
facilitate postoperative blood evacuation by preventing chest tube occlusion.[11] This 
system, which is placed in the operating room at the end of the procedure, is utilized in 
the ICU to prevent chest tube occlusion in the first 24 hours or until the patients stops 
bleeding during early recovery.  PleuraFlow was shown in pre-clinical studies to be 
highly effective in preventing RBS.[15, 16]  After initial regulatory approval, Montreal 
Heart Institute was the site of the world’s first human use of this technology.  All the 
surveyed surgeons noted that the device was not any more difficult to insert than a 
conventional chest tube and was easy to assemble and use.  A majority of surveyed 
nurses felt that the device was more time efficient than stripping, milking, or tapping 
the chest tubes to keep them open and felt it represented an easy to implement 
solution to the common problem of chest tube clogging.[17] In a subsequent study, it 
has been reported that the use of PleuraFlow in a universal use protocol significantly 
reduces RBS and POAF.  Study results showed a statistically significant 42% reduction 
in re-interventions for RBS complications among a 256 patient cohort where the 
PleuraFlow® system was used prospectively in comparison to a 1,849 historical cohort.  
Additionally, there was a statistically significant 30% decrease in POAF documented in 
the treatment group versus the historical control.[18]   
Given the findings that this device has already been shown to be readily implemented 
into our work flow in the ICU in a preliminary published study, and the new findings of 
reduced POAF and RBS, the purpose of this study is further evaluate these findings in a 
randomized controlled setting.  Therefore, we hypothesize that active clearance of chest 
tubes to optimize evacuation of shed mediastinal blood in the immediate postoperative 
period will reduce the incidence of re-interventions for POAF and RBS and lower overall 
morbidities after cardiac surgery.  Should this prove to be a valid hypothesis, protocols 
to keep chest tubes patent in the early hours after cardiac surgery can be developed 
and implemented. 
5 
Device 
The PleuraFlow® system is a commercial product regulatory cleared in the United States 
(US) (K093565) and by Health Canada.  It will be used according to indications for use 
and the current Instructions for Use (IFU). 
The PleuraFlow® Active Clearance Technology® System consists of a PleuraFlow® chest 
tube (PF-CT) and PleuraFlow® Clearance Apparatus (PF-CA). Together these two pieces 
make up the PleuraFlow® System. The device incorporates an integrated internal tube 
Clearance Apparatus designed to maintain patency of the chest tube, thus enhancing 
fluid evacuation from the thoracic cavity.  The active mechanism consists of an external 
to internal magnetic coupling that controls the movement of a metal wire inside the 
chest tube.  Movement of the internal wire to clear the chest tube is actuated 
externally, without breaking the internal sterile field (see Figure 1).  The PleuraFlow® 
ACT® has been tested in an experimental animal model at the Cleveland Clinic.1)12 In a 
head to head comparison with a same sized conventional 32 Fr chest tube in the setting 
of heavy bleeding, the PleuraFlow® drained significantly more, and significantly 
prevented residual hemothorax.1)13 When the 20 Fr minimally invasive system was 
tested against a 32 Fr conventional tube, again there was significantly superior 
drainage and significantly less retained blood and clot with the PleuraFlow® System. 
This was the first time a small diameter drainage tube was found to be superior to a 
larger diameter tube.1)14 During initial clinical use physicians and nurses rated the 
PleuraFlow® system positively for its ability to be incorporated into the postoperative 
workflow of managing the drainage of patients after heart surgery.1)15 

 
 
 
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Rev. 4, Febuary 2016 
 
 
Figure 1: The PleuraFlow® ACT® System Overview 
Guide Tube 
Chest Tube 
Clearance Wire 
Proximal Connector 
Shuttle Guide 
External Magnets 
Clearance Wire 
Loop 
Internal Magnets 
 
 
6 
Indications for Use and Contraindications: 
6.1 Indications 
The PleuraFlow® ACT® System is indicated for use as an adjunctive device during 
open surgical procedures in order to prevent fluid accumulation within the operative 
site after closure of the surgical wound. The device is indicated for use in thoracic 
surgical procedures. 
6.2 Contraindications 
The PleuraFlow® System is contraindicated for patients with a history of intolerance 
to implantable silicone materials. 
7 
Good Clinical Practice 
This clinical investigation will be conducted in compliance with regulatory requirements 
intended to: 
• 
Protect the rights, safety and well-being of human subjects; 
• 
Ensure the scientific conduct of the clinical investigation and the credibility of 
the clinical investigation results; 
• 
Define the responsibilities of the manufacturer and principal investigator, and; 
Assist sponsors, investigators, ethics committees, regulatory authorities and other 
bodies involved on the conformity assessment of medical devices. 
 
 
 
 
 
 
 

 
 
 
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8 
Study Design 
This is a prospective, randomized, two-arm, single blinded, single-center Post Market 
Clinical Follow-Up (PMFC) study. An interim analysis allowing for an early look at 
efficacy is planned after 300 randomized subjects have completed their 30-day follow-
up. This interim analysis is proposed following the results of a retrospective study 
done at the Montreal Heart Institute on more than 300 patients, comparing AF rate 
between patients with pleuraflow and control patients.  After a propensity score 
adjustment, a difference of 16% was obtained (AF rate of 9% in the pleuraflow group 
vs 25% in the control group). Since this might be a sign that the difference between 
the two arms is larger than expected, an interim analysis is planned after 300 
patients. 
8.1 
Test Arm 
The test arm consists of consecutively enrolled cardiac surgery patients receiving < two 
(2) PleuraFlow® chest tubes with Active Clearance Technology® and < two (2) other 
commercially available standard chest tubes. 
8.2 
Control Arm 
The control arms consist of consecutively enrolled cardiac surgery patients receiving < 
four (4) commercially available standard chest tubes. 
8.3 
Control and Test Arms 
In all arms, one (1) chest tube must be placed in the anterior mediastinum. The other 
chest tube(s) may be placed at the discretion of the operator. Chest tubes with internal 
diameter 28 FR to 32 FR shall be used for the single anterior mediastinal chest tube.  
The Montreal Heart Institute is required to participate in a pre-study roll-in phase prior 
to participating in this clinical study.  The purposes of the pre-study roll-in phase are 
to: 
- 
Allow the users at participating sites to familiarize themselves with the product 
use and with ACT; 
- 
Implement Clinical Use Protocols provided by ClearFlow, Inc. to all commercial 
users as part of product training, and; 
- 
Demonstrate consistency and compliance with the clinical use protocols. 
Pre-study roll-in phase requirements are: 
- 
Consecutive use of PleuraFlow® system on patients having cardiac surgeries 
during a 1 month period.  

 
 
 
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Rev. 4, Febuary 2016 
 
9 
Study Population 
9.1 
Demographics 
-Up to 508 evaluable post-cardiac surgery female and male subjects, 18 years of 
age and older will be consecutively enrolled in the study. 
- Subjects are required to meet all inclusion criteria and none of the exclusion 
criteria to be included in this PMCF study.  Subjects must be informed about this 
study and a written and signed informed consent must be obtained from the 
subject prior to cardiac surgery. 
9.2 
Inclusion Criteria 
Subjects will be required to meet all Inclusion Criteria:  
9.2.1 Admission for CABG, valve replacement or valve repair surgery, or a 
combination of these surgeries. Surgery must be done through a 
mediansternotomy; 
9.2.2 Procedure on ascending aorta and/or aortic arch that do not require deep 
hypothermic arrest (defined as < 14° C); 
9.2.3 Must be in sinus rhythm (SR) for previous 30 days prior to the index surgery 
and at the start of the index surgery. No patient with history of atrial 
fibrillation; 
9.2.4 Sign the Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) approved Informed Consent Form after the nature of the study has 
been explained and questions/concerns have been addressed. 
9.3 
Exclusion Criteria 
Subjects will be required to meet none of the Exclusion Criteria: 
9.3.1 
Admitted for surgical treatment of arrhythmia; 
9.3.2 
Admitted for cardiac surgery requiring implantation/explantation of a 
Ventricular Assist Device (VAD) or heart transplant; 
9.3.3 
Cardiac surgical procedure that requires deep hypothermic arrest (as 
defined above); 
9.3.4 
Admitted for Transcatheter aortic valve replacement (TAVR); 
9.3.5 
New or active endocarditis or myocarditis that is not adequately 
controlled with medication and/or requires surgical intervention; 
9.3.6 
Documented inherited bleeding disorders; 
9.3.7 
History or known allergies to the device materials; or 
9.3.8 
Participation in another clinical investigation. If a subject has recently 
completed participation in another drug or device clinical investigation, 
the subject must have completed that study at least thirty (30) days 
prior to being enrolled in this clinical study. 
 

 
 
 
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Rev. 4, Febuary 2016 
 
10 
Procedural Steps and Methods 
This study is on label and, accordingly, there are no specific procedures to follow.  The 
test article (PleuraFlow® System) will be used at the end of the cardiac surgery per 
standard of care.  The Sponsor is blinded to the study results.  Data will be revealed to 
the Sponsor after the last enrolled subject has exited the study (end of postoperative 
day 30 or hospital discharge, whichever occurs last). 
10.1 
Informed Consent and Subject Enrollment 
Investigators shall obtain a signed informed consent from each subject before 
enrolling as a study subject.  Each subject shall sign and date the IRB/IEC 
approved Informed Consent Form (ICF).  A subject who is unable to read and/or 
provide signature can participate in this clinical study, provided that a legal 
representative with signature authority signs and dates the ICF on behalf of the 
subject. 
Subjects shall be given sufficient time to review the ICF and ask questions before 
signing.  The investigator or designee shall be available to answer any questions 
about this clinical study.  An independent witness shall be present during the 
consenting process, and will sign and date the ICF. 
The device and procedures that are part of this PMFC study are performed after a 
scheduled cardiac surgery and are part of routine standard of care.  There are no 
procedures or treatments that are required for the purposes of the study. The 
research part of the study is the data collection of subjects’ history, peri- and 
post-cardiac surgery and postoperative clinical appointment. 
 
10.2 
Screening and Enrollment 
Participating sites shall screen consecutive patients who are admitted for cardiac 
surgery.  Patients who could meet the study eligibility criteria will be offered to 
participate in this clinical study.  Screen failures and reason(s) for screen failure 
shall be documented on study-specific logs and provided to the Sponsor 
periodically. 
Patients who meet the clinical study eligibility criteria and sign the ICF shall be 
enrolled and randomized prospectively before surgery to either receive the test 
article (PleuraFlow® System) and other commercial chest tubes (test arm), or to 
receive commercial chest tubes only (control arm), as part of their cardiac surgery 
(day 0).  Any commercial chest tube is eligible for use in this clinical study. 
Enrollment period is from consent through 30 days post index surgery. 
 
10.3 
Training 
                Product Training 
Prior to initiation of the trial, a ClearFlow, Inc. representative will train the 
surgeons and the supporting staff in the operating room and in the intensive care 
unit (ICU) using a training curriculum. 
 
The device shall be used according to the commercial IFU (Manual of Operations). 
ClearFlow, Inc. has created Clinical Use Protocols (Manual of Operations) for the 
use of PleuraFlow® ACT®. The Clinical Use Protocols are in accordance with the 
IFU. Users will follow the specific procedural steps outlined in the attached 
commercial Clinical Use Protocols (Manual of Operations). 

 
 
 
17 
Rev. 4, Febuary 2016 
 
Placement (locations) and number of PleuraFlow® System(s) and commercial 
chest tubes are dictated by this PMCF study protocol (See section 6). 
 
10.4 Documentation 
Training will be documented.  The trainee must sign and date the training record.  
Training must be completed and training records must be signed and dated 
before the staff is allowed to perform specific clinical investigation related tasks 
delegated to them by the PI. 
 
10.5 Randomization 
Subjects who meet eligibility criteria will be randomly assigned in a 1:1 fashion 
to either the Test arm or the Control arm.  
The point of randomization is before the start of the index surgery.  Subject 
assignment will be provided to the operating surgeon at that time. 
10.6 Follow-up Assessment 
Subjects will exit the study at the end of postoperative day 30 (midnight).  Clinical 
data will be collected through 30 days post index surgery.  This will include re-
admission for diagnosed POAF and/or RBS related occurrences within 30 days 
after the index surgery.  The patient will be considered as exited from the study at 
end of day 30 (midnight) post index surgery for the purposes of clinical data 
collection. 
10.7 Study Termination 
Subject participation is terminated at day 31 post index surgery.  
If a subject is re-admitted within 30 days after the index surgery to the treating 
hospital, a satellite clinic, or another hospital for any diagnosis of RBS and/or 
POAF-related occurrences, clinical data will be collected. 
 
Table 2: Subject participation and data collection period 
Discharge <30d*
Discharge >30d
Clinical 
data 
Y 
N 
* Including re-admission for RBS and/or POAF-related occurrences 
 <30d. 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Rev. 4, Febuary 2016 
 
11 
Safety Assessment and Medical Device Reporting 
The PleuraFlow® System is a Class II device in the US and approved device in Canada 
and a Class IIa device per rule 7 of Annex IX of Directive 93/42/EEC.  In its issuance of 
a substantial equivalence determination, the FDA did not require Sponsor to conduct a 
PMCF study.  This PMFC study is conducted on label.  Being marketed also in the 
European Community (EC), this study has to meet post-market surveillance 
requirements.  In the preface of MEDDEV 2.12/2 Rev 2 “Post Market Clinical Follow-Up 
Studies, A Guide for Manufacturers and Notified Bodies” it is stated: "Similarly when 
PMCF studies are conducted using CE Marked devices within their intended use, the 
provisions of Section 2.3.5 of Annex X of Directive 93/42/EEC do not apply. However, 
the provisions of Directive 93/42/EEC concerning information and notification of 
incidents occurring following placing devices on the market are fully applicable. 
Sponsor is subject to all requirements of 21 CFR Part 803 (MDR Reporting).  
Accordingly, Sponsor shall report all MDR reportable events (see definition) to FDA on 
Form FDA 3500A.  Sponsor shall review and evaluate all complaints (see definition) to 
determine whether a complaint represents an event that must be reported to FDA.  
Sponsor shall report an event upon becoming aware of information that reasonably 
suggests that the PleuraFlow® System has or may have caused or contributed to a 
death, serious injury, or has malfunctioned and that the device would be likely to cause 
or contribute to a death or serious injury if the malfunction were to recur.  Serious 
injuries where the device would be likely the cause of or contributed to shall be followed 
to resolution. 
The PI will evaluate and determine if the PleuraFlow® System has or may have caused 
or contributed to a death, serious injury, or has malfunctioned.  Sponsor has the right 
to request the steering committee to review the PI decision and concur or disagree.  In 
case the steering committee and PI disagree the steering committee adjudication 
prevails. 
11.1 Definitions 
Serious injury /(Serious illness) [21 CFR part 803.3(aa)(1)] is an injury or illness that: 
• is life threatening, even if temporary in nature; 
• results in permanent impairment of a body function or permanent damage to a body 
structure; or 
• necessitates medical or surgical intervention to preclude permanent impairment of a 
body function or permanent damage to a body structure. 
A malfunction [21 CFR Part 803.3(m)] is a failure of the device to meet its performance 
specifications or otherwise perform as intended.  Performance specifications 
include all claims made in the labeling for the device.  A malfunction should be 
considered reportable if any one of the following is true: 
• the chance of a death or serious injury occurring as a result of a recurrence of the 
malfunction is not remote; 
• the consequences of the malfunction affect the device in a catastrophic manner that 
may lead to a death or serious injury; 
• it causes the device to fail to perform its essential function and compromises the 
device's therapeutic, monitoring or diagnostic effectiveness, which could cause or 
contribute to a death or serious injury, or other significant adverse device 
experiences.  The essential function of a device refers not only to the device's 
labeled use, but for any use widely prescribed within the practice of medicine; 

 
 
 
19 
Rev. 4, Febuary 2016 
 
• it involves an implant malfunction that would be likely to cause or contribute to 
death or serious injury, regardless of how the device is used; 
• the device is considered life-supporting or life-sustaining, and thus essential to 
maintaining human life; or 
11.2 Reporting Requirements 
Investigators shall report to Sponsor PleuraFlow-related serious injuries as soon as 
becoming aware of the injury and no later than 48 hours. 
Investigators shall report deaths to both the Sponsor and Regulatory authorities in 
compliance with their applicable State, Country and conditions imposed by the 
reviewing Institutional Review Board (IRB). 
Sponsor shall take action under 21 CFR part 518 or part 806 of the FD&C Act as a 
result of the malfunction of the device. 
Sponsor shall also take action under MEDDEV 2.12/1 rev 8 Guidelines on a Medical 
Devices Vigilance System and under Health Canada Medical Device Regulations 
SOR/98-282, since the device is marketed under a CE Marking and Health Canada 
license. 
Sponsor’s reporting requirements are listed in Table 3. 
Table 3: Manufacturer’s Reporting Requirements and Timelines  
 
PleuraFlow® System: 
A) is marketed in the US 
B) has Canadian License  
C) has CE marking  
US 
MDR Action  
File MedWatch 
Report (form 
3500A)  
to FDA 
EU-MDV Action  
File Vigilance SystemReport 
Canadian MPR Action 
File Mandatory Problem 
Report 
Incident 
occurred 
in EEA 
Incident  
occurred 
outside 
EEA 
Incident 
occurred 
in 
Canada 
Incident  
occurred 
outside 
Canada  
 
and… 
 
 
Reporting Timeframe for 2, 5, 10, & 30 day reports, start the day after the first 
Company employee is notified. 
Report is to be sent within the time specified below. 
 
a malfunction were to occur 
that requires immediate remedial 
action to prevent an 
unreasonable risk of substantial 
harm to the public health (or as 
described in MEDDEV 2.12-1 for 
the EU, Serious Public Health 
Threat). 
Yes 
 
Initial Report 
5 working days 
Yes 
 
Initial Report 
immediately 
but not more 
than 2 
calendar 
days  
Yes 
 
Initial Report 
immediately but 
not more than 2 
calendar days* 
Yes 
 
On or before 
recall actions 
initiated; 
immediately 
without any 
delay which 
cannot be 
justified for 
serious 
public health 
issues 
Yes 
 
On or before 
recall actions 
are initiated for 
any corrective 
action; 
immediately 
without any 
delay which 
cannot be 
justified serious 
public health 
issues 
The FDA has identified an event, 
and submitted a written request 
to file a report, for all subsequent 
events of the same nature that 
involve similar devices for a 
specified time period. 
Yes 
 
5 working days 
 
 
N/A 
 
 
N/A 
 
 
N/A 
 
 
N/A 
FDA and CMDR  
Information reasonably suggests 
a death or serious injury / 
Yes 
 
30 days 
 
 
NA 
 
 
NA 
Yes 
 
Preliminary 
Yes 
 
Preliminary 

 
 
 
20 
Rev. 4, Febuary 2016 
 
deterioration of health has 
occurred and was caused or 
contributed to by a device 
manufactured by our company. 
 
Report 
immediately 
without any 
delay which 
cannot be 
justified and 
not more 
than  
10 days 
Report 
immediately 
without any 
delay which 
cannot be 
justified and not 
more than 10 
days if 
corrective action 
is initiated
MDD 
Information reasonably suggests 
a death or unanticipated 
serious deterioration of health 
has occurred and was caused or 
contributed to by a device 
manufactured by our company.  
 
 
NA 
Yes 
 
Initial Report 
immediately 
but not more 
than 10 
calendar 
days 
No 
 
 
 
NA 
 
NA 
A malfunction has occurred with 
the PleuraFlow® System and 
would be likely to cause or 
contribute to a death or serious 
injury if the malfunction were to 
recur.  
Yes 
 
30 days 
Yes 
 
Initial Report 
immediately 
but not more 
than 30 
calendar 
days 
No 
 
 
Yes 
 
Preliminary 
Report 
immediately 
without any 
delay which 
cannot be 
justified and 
not more 
than  
30 days 
Yes 
 
Preliminary 
Report 
immediately 
without any 
delay which 
cannot be 
justified and not 
more than 30 
days if 
corrective action 
is initiated 
Additional information becomes 
available after the initial report 
has been submitted.
Supplemental 
Report 
 
Final Report 
 
NA 
 
Final Report 
 
Final Report 
A systematic Recall has been 
initiated due to risk of Death or 
Serious Injury (reported to a 
Regulatory Agency)  
Yes 
 
Submit Report 
Within 10 
working days  
of initiating 
action 
Yes 
 
On or before 
initiating 
recall actions 
Yes 
 
On or before 
initiating recall 
actions 
Yes 
 
Before and 
after 
initiating 
recall actions 
Yes 
 
On or before 
recall action; 
indicating to or 
requested to 
take such 
actions by a 
Regulatory 
Agency 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
21 
Rev. 4, Febuary 2016 
 
12 
Data  
Data is collected on Case Report Forms (CRFs).  Electronic Data Capture (EDC) system 
will be used to enter data.  Manual (paper) CRF samples are provided in the study 
Manual of Operation. 
Source data shall be used to complete the study CRF.  Source data consist of all 
information in the patient health record with the exception of Personal Health 
information (PHI).  These include hospital records, records from doctor office visits, 
clinic visits, hospital re-admission after discharge and up to 30 days after the index 
surgery, laboratory results and clinical staff notes. 
Source documents, if not in electronic format, should be completed legibly, in dark ink, 
typewritten or generated by testing equipment.  Any necessary corrections should be 
made by a single strikethrough in ink, initialed and dated by the person who makes 
the change on the day the change is made. 
Upon CRF completion, the Investigator should sign and date each CRF that bears a 
signature line.  Completed CRFs shall be monitored and collected during periodic site 
visits.  Source documents and copies of CRFs shall be available for review by the study 
sponsor, monitor and authorized regulatory bodies. 
12.1 
Protection of Patient Privacy and Confidentiality of Patient Information 
The PMCF study will be conducted in accordance with GCP. Subject confidentiality shall 
be maintained at all times throughout the conduct of this trial and all subject data shall 
be maintained secure against unauthorized access.  Possible review and photocopying 
of the subject’s records by the IRB, Health Canada or FDA representatives could occur.  
In addition, ClearFlow, Inc., the manufacturer, and its representatives will review and 
photocopy anonymized subjects’ records as part of monitoring activities aimed at 
assuring the accuracy of the data collected from the subject health record per 
requirements of this study protocol. 
All data entered into the database are anonymized.  Patient Health Information (PHI) 
will not be collected.   
Identifiable information of all subject records to be reviewed per the above must be 
blacked out (de-identified) and only the subject’s study number used as tracking 
information.  Individual subject’s data will not be used for educational, presentation 
and/or publication purposes. 
Photographs of the chest tubes used in this study may be taken after removal from the 
patient to document chest tube patency. 
Regulatory agencies and ClearFlow, Inc. are required to maintain the privacy of all 
records they review in connection with this study. 
The user interface to the EDC is password protected.  Only approved site personnel, 
trained on the use of EDC will be allowed password-protected access to the EDC for 
the purpose of data entry.  All study documents and data elements will identify 
patients by their unique subject identification (ID) number. 
12.2 
Data Monitoring 
Trained monitors will conduct periodic site monitoring visits.  Purpose of the visits is to 
verify that data entered to the study database matches the source data.  Monitors will 
coordinate visits with the site personnel. 

 
 
 
22 
Rev. 4, Febuary 2016 
 
12.3 
Premature Study Termination 
In case the study is terminated prematurely, all subjects who have signed an informed 
consent, and were randomized to the test arm or to the control arm will be considered 
to have enrolled in the study. Subjects who complete the 30 day or index 
surgery/discharge (whichever occurs later) will be considered to have completed the 
study.  The reason for study discontinuation should be documented for each subject.  
12.4 
Close Out Activities 
Study close out activities include, and are not limited to the following documentation. 
-Data is entered into the database 
-All data queries are resolved 
-Regulatory and study specific documents and forms are in order 
-MDR reporting is complete 
-Communication to Principal Investigator on record retention, final report to 
IRB/EC, and potential regulatory audits. 
 
12.5 
Data Management 
Data will be collected and stored at the department of surgery of Montreal Heart 
Institute. Only the princiapal investigator and study coordinators will have access to 
the database. 
12.6 
Record Retention 
Record will be retain for a period of 5 years in the department of cardiac surgery of the 
Montreal Heart Institute. 
 

 
 
 
23 
Rev. 4, Febuary 2016 
 
13 
Investigator Responsibilities 
The Principal Investigator participating in this PMCF study must be a licensed physician in 
his/her state of employment.  The investigator will affirm by his/her signature on this study 
protocol and the Investigator’s Agreement that s/he will fulfill her/his responsibilities 
relative to this clinical investigation. 
The principal investigator shall: 
13.1 
Obtain IRB/IEC approval to conduct this PMCF study. Principal Investigator shall 
provide Sponsor with a written IRB approval of the study protocol and patient 
informed consent. 
13.2 
Adhere to its institutional, local and FDA rules and regulations regarding release 
of patient data. 
13.3 
Ensure that data is entered to the database in accordance with this protocol. 
13.4 
Ensure that all subjects sign and date the IRB/IEC approved ICF prior to 
performing any study-related procedures and that subjects entering the study 
conform to the study eligibility criteria. 
13.5 
Ensure that during the term of trial set forth in the clinical trial agreement, the 
Investigators engaging in the trial do not initiate any other clinical trial, which 
may affect recruitment of subjects for this trial; 
13.6 
 Ensure that qualified, instructed personnel and infrastructure e.g., 
documentation facilities, etc. are available for the trial and that the trial may 
also in other respects be conducted in safe conditions; 
13.7 
Ensure that the Investigators are familiar with the details of the protocol and 
other liabilities and responsibilities defined in the clinical trial agreement, and 
that Investigators are committed to act accordingly; 
13.8 
Ensure that the subjects are not simultaneously involved in any other clinical 
trials and that they are not subjects to any investigations differing from the 
trial protocol 
13.9 
Comply with reporting requirements outlined in Section 12.2. 
13.10 
Submit patient screening logs to Sponsor. 
13.11 
Allow monitoring and auditing at the trial site to be conducted by the SPONSOR 
/SPONSOR representative, as well as US regulatory authorities, and, if 
necessary, to assist in the executing thereof.  
13.12 
The Investigator should archive all documents relating to the trial (source 
documents) at the site for a period of 5 years.  In case the Investigator 
leaves the institution, it must be handed over to the successor. 
13.13 
Submit progress reports to the Sponsor.  A progress report shall summarize the 
number of enrolled patients and the number of CRFs with entered data that 
were transmitted/entered to the study data repository.  The progress report 
shall also document complaints reported by the site. 

 
 
 
24 
Rev. 4, Febuary 2016 
 
13.14 
Maintain trial records for a period of 5 years 
13.15 
Maintains study-related correspondence with IRB/IEC, FDA, sponsor and 
sponsor designees. 
13.16 
Register the trial on www.clinicaltrials.gov before starting the patient 
recruitment; 
13.17 
Inform the sponsor of the completion of the trial. 
 
14 
Sponsor’s Responsibilities 
The Sponsor of this PMCF study is ClearFlow, Inc. of Anaheim, CA, U.S.A. and the 
research found of the Montreal Heart Institute Cardiac surgery department. The 
Sponsor is committed to:  
14.1 
Conduct a site initiation visit after IRB/IEC approval of this investigational plan 
14.2 
Maintain compliance with all applicable regulations; 
14.3 
Protect the rights, health, safety and welfare of study subjects; the Sponsor is 
responsible for obtaining and reviewing copies of IRB or IEC approval 
documents and will verify that appropriate subject informed consent has been 
obtained; 
14.4 
Investigate all adverse events, determine reporting requirements and report to 
all applicable regulatory bodies worldwide, where the PleuraFlow® System is 
distributed. Report such events in accordance with 21CRF part 806, MEDDEV 
2.12/1 rev 8 Guidelines on a Medical Devices Vigilance System, MEDDEV 
2.12/2 rev 2 Post Market Clinical Follow Up studies, Health Canada Medical 
Device Regulations SOR/98-282, HIPAA requirements, the Declaration of 
Helsinki and the following International Harmonized Standards: ISO 
14155:2011 (E), and with applicable State, Country and conditions imposed 
by the reviewing Ethical Committee; 
14.5 
Provide the investigational Site with the necessary background information 
needed for the appropriate and safe conduct of the trial; 
14.6 
Inform the principal investigator of any new information about the study that 
may affect the health, safety or welfare of the subjects or which may 
influence their decision to continue participating in the study; 
14.7 
Contribute to the statistical analysis and study report-writing resources 
necessary to complete reporting of the study results; 
14.8 
Maintain all study documentation, including but not limited to, copies of 
correspondence, adverse events, customer complaints, records related to the 
signed investigator agreements and other records related to the clinical 
study; 
14.9 
Ensure necessary training and orientation of the investigators and other 
personnel of the investigational site involved in the trial in order to conduct 
the trial in accordance with the protocol and good clinical practice 
requirements.  Per the study protocol, training in the use of the PleuraFlow® 
System and case support are provided during the pre-enrollment phase 1 and 
subsequently, as necessary. 
 

 
 
 
25 
Rev. 4, Febuary 2016 
 
15 
Publication policy 
At the conclusion of this study, a manuscript (or manuscripts) shall be prepared for 
publication in a peer-reviewed scientific journal. Analyses for the publication will be 
generated from the study database.  The PI will oversee the publication. 
The clinical site has the right, consistent with academic standards, to publish their 
study results. This right is subject to this study agreement. The clinical study site 
agrees to submit any form of publication to ClearFlow, Inc. for review and approval 
prior to any submission but retains final approval over decisions related to content and 
journal for submission.  
16 
Liability 
The PleuraFlow® device is commercially available in the countries of participating sites. 
Sponsor carries product liability insurance with $5,000,000 aggregate/occurrence limit. 
17 
Study Committees 
 
17.1 
Steering Committee will: 
The study steering committee will consist of the Study coordination investigator and TBD.  
The study steering committee will: 
-Dr Philippe Demers, MHI;  
-Dr Louis P. Perrault, MHI;  
-Dr Denis Bouchard, MHI;  
-Dr Edward Boyle, Clearflow Inc. 
 
The study interim analysis will be verified by Dr Philippe Demers, MHI, to confirm 
continuation or end of the study. 
 

 
 
 
26 
Rev. 4, Febuary 2016 
 
 
18 
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