The PRICE Trial: Phlebotomy Resulting in Controlled Hypovolemia to Prevent Blood Loss in Major Hepatic Resections
Phase: NA
Conditions: Liver Neoplasms, Hepatectomy
Sponsor: Ottawa Hospital Research Institute

 
 
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Clinical Trial Protocol 
 
 
“The PRICE Trial: Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major 
hepatic resections” 
 
ClinicalTrials.gov: 
NCT02548910 
 
Version: 
5  
 
Funding: 
Ottawa Hospital Research Institute 
 
Canadian Association of General Surgeons 
 
 
Principal investigator:  
Guillaume MARTEL, MD, MSc, FRCSC, FACS 
 
Clinical Epidemiology Program, Ottawa Hospital Research Institute 
 
Department of Surgery, University of Ottawa 
 
501 Smyth Rd, CCW 1667 
 
Ottawa, ON, K1H 8L6 
 
Tel: +1-613-737-8899 ext. 71053 
 
Fax: +1-613-739-6854 
 
Email: gumartel@toh.on.ca 
 
 
Co-investigators: 
Dean A. FERGUSSON, PhD, MHA (Clinical Epidemiology) 
 
 
 
Elianna SAIDENBERG, MD, FRCPC (Hematology and Transfusion Medicine) 
 
 
 
Christopher WHERRETT, MD, FRCPC (Anesthesiology) 
 
 
Study coordinator: 
Aklile WORKNEH, MSc (Interdisciplinary Health Sciences) 
 
Tel: +1-613-737-8899 ext. 71484 
 
Email: aworkneh@ohri.ca 
 
 
 
 
Date: 
October 15, 2018 
 
 
 
 
 
OHSN-REB:  
 
20150919-01H 

 
 
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Table of Contents 
 
Table of Contents ........................................................................................................................................................... 2 
Synopsis .......................................................................................................................................................................... 3 
Abbreviations .................................................................................................................................................................. 4 
1 
Introduction .............................................................................................................................................................. 5 
1.1 
Background and Rationale ............................................................................................................................ 5 
1.2 
Objectives and Outcome Measures ............................................................................................................ 9 
1.3 
Trial Design ..................................................................................................................................................... 9 
2 
Methods: Participants, Intervention, and Outcomes ......................................................................................... 9 
2.1 
Study Setting ................................................................................................................................................... 9 
2.2 
Eligibility Criteria ............................................................................................................................................. 9 
2.3 
Interventions .................................................................................................................................................. 10 
2.4 
Outcomes and Timeline .............................................................................................................................. 13 
2.5 
Sample Size .................................................................................................................................................. 13 
2.6 
Recruitment ................................................................................................................................................... 13 
3 
Methods:  Assignment of Interventions ............................................................................................................. 14 
3.1 
Allocation ....................................................................................................................................................... 14 
3.2 
Blinding .......................................................................................................................................................... 14 
4 
Data Collection, Management, and Analysis ................................................................................................... 14 
4.1 
Data Collection Methods ............................................................................................................................. 14 
4.2 
Data Management ........................................................................................................................................ 15 
4.3 
Statistical Methods ....................................................................................................................................... 15 
5 
Methods: Monitoring ............................................................................................................................................ 16 
5.1 
Data Monitoring ............................................................................................................................................ 16 
5.2 
Harms ............................................................................................................................................................. 16 
5.2.1 
Adverse Events ..................................................................................................................................... 16 
5.3 
Auditing .......................................................................................................................................................... 16 
6 
Ethics and Dissemination .................................................................................................................................... 17 
6.1 
Research Ethics Approval ........................................................................................................................... 17 
6.2 
Protocol Amendments ................................................................................................................................. 17 
6.3 
Consent .......................................................................................................................................................... 17 
6.4 
Participant Confidentiality............................................................................................................................ 17 
6.5 
Declaration of Interests................................................................................................................................ 17 
6.6 
Access to Data .............................................................................................................................................. 17 
6.7 
Ancillary and Post-trial Care ....................................................................................................................... 18 
6.8 
Dissemination Policy .................................................................................................................................... 18 
7 
References ............................................................................................................................................................ 19 
8 
Appendices ............................................................................................................................................................ 21 
8.1 
Appendix 1: Dindo-Clavien Classification of Surgical Complications [from 35] .................................. 21 
8.2 
Appendix 2: PRICE trial surgeon perception scale ................................................................................. 22 
8.3 
Appendix 3: PRICE trial eligibility form ..................................................................................................... 23 
8.4 
Appendix 4: PRICE trial Case Report Forms (CRFs) and source documentation ............................. 25 
8.5 
Appendix 5: Adverse Event/Serious Adverse Event Case Report Form ............................................. 38 
8.6 
Appendix 6: Informed consent, English and French ............................................................................... 38 
 
 

 
 
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Synopsis 
 
Study Title 
The PRICE Trial: Phlebotomy resulting in controlled hypovolemia to 
prevent blood loss in major hepatic resections 
Short title 
The PRICE trial 
Study Design 
Double-blind randomized control trial 
Study Participants 
Any patient being considered for a major elective liver resection will 
be considered for trial enrollment. Patients undergoing a posterior 
right lobe or a central resection will also be considered. 
Planned Sample Size 
62 
Planned Study Period 
2 years 
 
Objectives 
Outcome Measures 
Primary 1 
 
To determine whether the use of 
phlebotomy compared to standard 
of care prior to liver resection leads 
decreased operative blood loss 
Intraoperative blood loss 
Primary 2 
To determine trial feasibility 
Trial accrual 
Secondary 1 
 
To determine whether phlebotomy 
leads to decreased blood product 
transfusion 
Blood product transfusion rate 
Secondary 2 
 
To determine whether phlebotomy 
leads to decreased perioperative 
morbidity 
30-day perioperative morbidity 
rate  
Secondary 3 
To 
determine 
the 
safety 
of 
phlebotomy compared to standard 
of care 
7-day morbidity and mortality 
Secondary 4 
 
To determine whether phlebotomy 
leads to easier liver parenchymal 
transection. 
Surgeon perception scale 
 

 
 
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Abbreviations 
 
ALT 
Alanine aminotransferase 
ANH 
Acute normovolemic hemodilution 
CI 
Confidence Intervals 
cm 
Centimeter 
CPDA 
Anticoagulant citrate phosphate dextrose adenine solution 
CRF 
Case report form 
CVC 
Central venous catheter 
CVP 
Central venous pressure 
DSMB 
Data safety monitoring board 
g 
Gram 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GP 
General Practitioner 
H2O 
Water 
HF 
Heart failure 
HPB 
Hepato-pancreato-biliary 
ICMJE 
International Committee of Medical Journal Editors 
ID 
Identification 
INR 
International normalized ratio 
IV 
Intravenous 
kg 
Kilogram 
mL 
Milliliter 
MRN 
Medical record number 
NYHA 
New York Heart Association 
OHRI 
Ottawa Hospital Research Institute 
OHSN-REB 
Ottawa Health Science Network Research Ethics Board 
OR 
Odds ratio 
PHI 
Personal health information 
PI 
Principal Investigator 
PII 
Personal identifying information 
REB 
Research Ethics Board 
RR 
Risk ratio 
 

 
 
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1 
 Introduction 
1.1 
Background and Rationale 
Major liver resections are now commonly performed in specialized hepatobiliary surgical units. The 
indications for liver surgery include primary and metastatic liver cancers, as well as numerous benign 
conditions such as liver cysts, major bile duct injuries, liver adenomas or living-donor transplantation. The 
need for major liver surgery is growing exponentially in our society, as a result of the known increase in the 
incidence of liver cancer in North America, the evolving obesity epidemic leading to non-alcoholic 
steatohepatitis and cirrhosis, improved chemotherapeutic drugs leading to more patients being candidate 
for liver surgery, as well as the dramatic rise in the utilization of modern imaging techniques leading to the 
incidental diagnosis of numerous benign and malignant liver conditions. Importantly, the growing need for 
liver surgery affects all age, gender and ethnic groups,  as certain conditions such as adenomas 
predominantly affect young healthy women, while liver cancer tends to affect middle-age and older patients. 
Finally, the advent of living-donor liver transplantation and the known shortage of deceased-donor organs 
lead many young and middle-aged adults to undergo major liver resections.  
Liver surgery is highly complex and associated with significant healthcare costs, owing to its 
technical nature and significant perioperative complication rates. As recently as 1970, the reported 
operative mortality rate associated with liver surgery was as high as 17-24% [1], owing in large part to 
major hemorrhage [2]. Today, the average mortality rate following liver resection is 3.6% in a recent 
systematic review of the literature [3]. In the Province of Ontario, mortality rates of less than 3% are now 
routinely expected in liver surgery [4]. Despite improvements in perioperative mortality rates, perioperative 
morbidity rates remain as high as 50% in major series. Although patients undergoing liver surgery have 
benefited over the years from tremendous improvements in resection techniques, anesthesia and critical 
care, these operations remain fraught with complications owing in part to the risk of major intraoperative 
blood loss and hemorrhage.  
 
Blood loss and blood transfusion are common complications in liver surgery: Despite major 
improvements in perioperative morbidity and mortality following liver surgery, major blood loss and blood 
transfusion remains a significant concern for surgeons, anesthesiologists and patients [5, 6]. Among high-
volume institutions, median intraoperative blood loss during liver resection is between 300-800 mL [7-11]. 
The associated risk of blood transfusion is 17-41% [7-12]. Population-based analysis from the American 
College of Surgeons National Surgical Quality Improvement Program dataset reveals a transfusion rate of 
22% among 2,448 hepatectomies performed in the United States in 2013 at 85 centers [12]. At our own 
center, review of data for a one-year period (2011-2012) of an electronic registry reveals median blood loss 
of 475 mL for all liver resections, 775 mL in major liver resections, and a 22% transfusion rate during 
hospitalization. A median of 2 units of packed red blood cells were given to transfused patients. Between 
1995 and 2004, well over 10,000 liver resections were performed in Canada [13], and this figure has 
undoubtedly increased since then. Based on the above figures, one can estimate that liver resection is 
associated with the transfusion of approximately 440 units of blood per year in this country. 
 
Risk and cost associated with blood loss and blood transfusion: Blood loss in liver resection is 
strongly associated with worse perioperative morbidity and mortality, independently from blood transfusion 
[8, 10, 14]. Jarnagin et al. have demonstrated in a large dataset comprising 1,803 patients that operative 
blood loss was independently associated with both, perioperative morbidity (OR 1.35, 95% CI 1.18, 1.55) 
and mortality (OR 1.69, 95% CI 1.44, 1.99) [8]. Excessive blood loss also renders liver surgery much more 
technically challenging, particularly when it originates from deep hepatic vein branches during transection 
of the liver parenchyma [15]. This type of brisk venous bleeding can rapidly obscure the surgical field and 
jeopardize the safety of resection. 
Transfusion of blood products is associated with the rare risk of transmission of infectious diseases, 
transfusion reaction and clerical errors, and creates pressures for the national blood supply [16]. Moreover, 
blood transfusion is thought to have immunomodulatory effects, which may be associated with increased 
infectious complications, delayed postoperative recovery, as well as worsen long-term cancer-specific 
survival [17-19]. In a recent manuscript by Hallet et al, blood transfusion was independently associated with 
worsened 5-year overall survival and recurrence-free survival following liver resection for metastatic 
colorectal cancer [18]. Finally, blood transfusion is associated with a significant societal cost. A 2002 
publication estimates the cost of one unit of allogeneic packed red blood cell to be US$ 264.81 [20]. Given 
the increasing incidence of liver resection and the need for transfusion in about one quarter of patients for a 
median of 2 units, it becomes clear that blood loss and blood transfusion are both important independent 
contributing factors to poor outcome and high societal cost following liver surgery.  

 
 
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Methods used to prevent blood loss during liver surgery: In order to minimize blood loss and blood 
transfusion in liver surgery, numerous cardiovascular, pharmacologic and surgical interventions have been 
devised (table 1). The evidence base supporting each intervention is highly variable. In clinical practice, 
surgeons and anesthesiologists utilize a widely variable combination of these techniques, based on 
personal experience and interpretation of the literature. 
 
Table 1. Interventions to decrease blood loss and blood transfusion in liver surgery 
Pharmacologic 
Cardiovascular 
Surgical 
Antithrombin III 
ANH 
Hepatic inflow occlusion 
Aprotinin 
Autologous blood donation 
Topical agents 
Desmopressin 
Hypoventilation 
Energy transection devices 
Recombinant factor VIIa 
Low CVP 
Transection methods 
Tranexamic acid 
Phlebotomy 
 
Abbreviations – ANH: acute normovolemic hemodilution; CVP: central venous pressure 
 
Liver resection performed under conditions of low central venous pressure (CVP) (<5 cm H2O) is 
widely regarded as the standard of care. Numerous studies have demonstrated that intraoperative blood 
loss during liver resection is almost linearly associated with CVP [21-24]. For instance, Jones et al. 
demonstrated that with a CVP of 5 cm H2O or less median blood loss was 200 cc compared with 1000 mL 
over 5 cm H2O (p=0.0001) [21]. In a recent meta-analysis of randomized trials, patients undergoing liver 
resection under low CVP conditions lost significantly less blood (-419 mL [95% CI -575, -264], p<0.00001) 
and demonstrated a trend towards fewer transfusions (RR 0.66 [95% CI 0.42, 1.03], p=0.067) [25]. Low-
CVP liver surgery is widely adopted, both based on the available data and its physiologic soundness. In a 
recent survey of liver surgery centers in North America, Europe and Asia, Mise and colleagues reported 
that 85% of centers routinely restrict intraoperative fluid administration in an effort to lower the CVP [26]. 
Similarly, all recently surveyed Canadian liver surgeons report targeting a low CVP frequently or always 
during liver resection [27]. A low CVP is thought to reflect a lower pressure within the right atrium and 
inferior vena cava. As a consequence, the proximal pressure within the hepatic veins is also likely lower, 
which leads to less pronounced blood loss from hepatic vein branches during the liver parenchyma 
transection. As Alkozai and colleagues have argued (figure 1), the largest proportion of blood loss in liver 
surgery occurs during the parenchymal transection and is most likely to be influenced by the filling status of 
the patient and the associated CVP [5]. 
 
Figure 1. The mechanisms of bleeding and the relative amount of blood loss (dotted line) during the three surgical 
stages of partial liver resections. From Alkozai et al. [5], with permission 
 
 
 

 
 
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Intraoperative CVP can be controlled by the anesthesiologist using a variety of techniques. Most 
commonly, the patient is kept relatively intravascularly volume depleted by minimizing intravenous fluid 
administration. Other techniques can be used to supplement the use of intravenous fluid management, 
such as hypoventilation, as well as the use of diuretics or venous vasodilating agents.   
 
Phlebotomy and controlled hypovolemia to prevent blood loss in liver surgery: Intraoperative 
phlebotomy and controlled hypovolemia is a novel intervention that can be used to decrease blood loss and 
blood transfusion in elective liver surgery. This simple intervention consists of the removal of whole blood 
from the patient prior to the initiation of parenchymal liver transection. Following removal of the portion of 
liver, the phlebotomized blood is given back to the patient. 
Whole blood phlebotomy leads to a decrease in the net circulating volume and results in a mild to 
moderate decrease in CVP. Acute phlebotomy of 8 mL/kg is thought to decrease the circulating blood 
volume by 10-12% [28], a state that is comparable to class 1 early hemorrhage. Class 1 hemorrhage is 
considered a non-shock state that is comparable to the donation of one unit of whole blood [29]. Acute 
blood loss of less than 15% of the total blood volume leads to arterial baroreceptor response, which in turn 
leads to increased sympathetic tone and decreased vagal tone [30]. This leads to compensation, primarily 
in the form of increased peripheral vascular resistance, leading to maintained arterial blood pressure and 
critical tissue perfusion [30]. At 10-15% of blood volume loss, cardiac output decreases minimally, as do 
right arterial pressure and CVP. 
Whole blood phlebotomy has not been used widely in elective liver resection. Hashimoto and 
colleagues have reported the results of a small trial comparing phlebotomy (0.7% of body weight or 7 g of 
blood/kg) versus control in 79 patients undergoing living donor liver resection [15]. This study yielded a 
difference in parenchymal transection blood loss (140 mL vs. 230 mL, 2.15 mL/cm2 vs. 3.75 mL/cm2) 
favoring the phlebotomy group. Given that blood loss in living donor liver resection is typically extremely low 
these results were considered clinically significant. That said, this trial also utilized autologous blood 
donation, which may have confounded the results. One other small trial of 30 patients published only in 
Chinese would also suggest that phlebotomy with controlled hypovolemia resulted in decreased blood loss 
and blood transfusion [31]. 
In the context of liver transplantation, Massicotte and colleagues have carried out a before-and-after 
study, where intraoperative phlebotomy was utilized as part of a novel management protocol, which also 
included the use of cell saver, the avoidance of blood product transfusion, and the minimization of 
intravenous crystalloid administration [31]. In this work, where 0% vs. 44.5% of patients underwent 
phlebotomy, both blood loss (1,479 vs. 903 mL) and red cell transfusion (2.8 vs. 0.4 units/patient) were 
significantly decreased, together with lower CVP prior to caval clamping (9.2 vs 6.4 cm H2O). Another study 
has further examined the effect of phlebotomy followed by phenylephrine infusion in patients undergoing 
pre-transplantation perihepatic dissection [28]. They reported that phlebotomy decreased CVP and portal 
venous pressure (PVP). Following phenylephrine infusion to restore arterial pressure, PVP was unaffected, 
while CVP increased without accurately reflecting changes in cardiac filling. 
In addition to the above work, our group has acquired experience with 23 patients who underwent 
phlebotomy prior to elective major liver resection [32]. In this cohort, phlebotomy of 5.3-10.1 mL/kg was 
successfully carried out with a median total intraoperative blood loss of 375 mL or 4.7 mL/kg and 8.7% 
transfusion rate, which compares favorably with our 2011-2012 cohort of major resections that had a 
median blood loss of 775 mL. Massicotte et al. also reported using phlebotomy for elective liver resections, 
although they did not specifically provide data on these patients [33]. Finally, in a survey of worldwide liver 
surgery centers, a small number of centers reported using phlebotomy in the event that hepatic vein 
bleeding was excessive during liver transection [26]. 
 
Difference with acute normovolemic hemodilution: The reader could confuse phlebotomy in liver 
surgery with acute normovolemic hemodilution (ANH). ANH, in contrast to simple phlebotomy, is a 
technique that has been used in a number of operative disciplines such as thoracic surgery, urology, and 
liver surgery. ANH consists of withdrawal of large volume of whole blood to achieve target hemoglobin of 
80 g/L, followed by the purposeful replacement of the lost blood with intravenous crystalloid and/or colloid 
to maintain euvolemia rather than hypovolemia. During the procedure any lost blood is thought to be more 
diluted. The whole blood that is removed before the procedure is given back to the patient at the end of the 
surgery.  
ANH has not gained wide acceptance in elective liver surgery. Reasons for this include that ANH 
may in fact render the liver operation technically more challenging based on the high volume of 
administered fluid to maintain euvolemia, the lack of objective decrease in intraoperative bleeding, as well 
as the cumbersome nature of the procedure. In contrast, phlebotomy involves the withdrawal of a much 

 
 
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smaller blood volume (7-10 mL/kg), without subsequent replacement with intravenous fluids [15, 28, 33]. A 
typical patient undergoing phlebotomy would have approximately 500-700 mL removed, whereas the 
average volume removed with ANH by Jarnagin et al. was 2,250 mL [34]. This is a critical distinction, which 
leads to a different mechanism of action. Phlebotomy leads to controlled hypovolemia, rather than 
euvolemia, as in the case of ANH. This is postulated to lead to decreased blood loss and decreased 
requirement for blood transfusion.  
 
Safety considerations with phlebotomy in liver surgery: Intraoperative phlebotomy for elective liver 
surgery should be considered a simple and safe intervention. The following lines of argument support this 
position: 1) phlebotomy is already being performed in clinical practice; 2) other interventions are similar to 
phlebotomy with satisfactory safety profiles; and 3) the risks associated with phlebotomy are known and 
can thus be anticipated and prevented. 
 
Phlebotomy in clinical practice: Phlebotomy has been utilized in clinical practice for several hundreds of 
patients. Two small trials have included a total of 49 patients undergoing phlebotomy for liver resection, 
with excellent safety profiles [15, 31]. As well, phlebotomy has been routinely used in some centers for liver 
transplantation, which typically applies to much sicker patients with highly disturbed physiology [28, 33]. 
None of these patients required dialysis. Massicotte et al. have also reported employing this technique in 
elective liver resections [28]. Finally, our own group has acquired experience with 26 such patients and 
have observed no major (Clavien-Dindo grade 3a or greater) complications [35]. 
 
Other similar interventions: Phlebotomy, by virtue of the blood drawing, can be compared to ANH. The 
use of ANH is a well-known technique in anesthesia. It has been described extensively and tested in over 
40 randomized controlled trials in various fields of surgery [36]. In this current trial, we have incorporated 
exclusion criteria that are conservative and were modeled after the ANH experience in liver surgery [34]. In 
that trial, there was no difference in perioperative morbidity between ANH and control. 
 
Expected risks associated with phlebotomy: There are few risks directly attributable to phlebotomy. 
However, a small volume of phlebotomy could potentially lead to any physiologic effect associated with 
blood loss. These effects could have implications for any major organ system, due to decreased perfusion 
(eg. myocardial ischemia, cerebrovascular accident, acute renal failure, coagulopathy, hepatic insufficiency, 
etc.). That being said, these risks exist with liver surgery, whether or not a phlebotomy is performed, simply 
on the basis of potential significant blood loss. In order to be considered fit enough for liver surgery; 
patients cannot have excessive comorbid illnesses that could be grossly exacerbated by the operation. The 
patient population that is thus considered for surgery is a relatively fit one that can tolerate phlebotomy. 
Furthermore, the inclusion and exclusion criteria that have been built in the protocol exclude those at a 
greater risk of adverse event associated with decrease organ perfusion.  
Other potential risks associated with phlebotomy pertain to the collection of whole blood and its 
auto-transfusion at the end of surgery. There is a potential risk for clerical error with the blood. Similarly, 
there is a theoretical risk of bacterial contamination of the collection bag, tubing, and as a consequence, 
whole blood. To minimize these risks, all study procedures have been developed conjointly between 
surgery, anesthesia, and the Transfusion Medicine department at our center. The collection bags will be 
provided by Transfusion Medicine, labeled with the patient identifier, handled and processed in the same 
manner as any other blood product in the operating room. This procedure will allow for the safe handling of 
all blood specimens, in accordance with all protocols already in place at our center.  
 
Why study phlebotomy and controlled hypovolemia? Whole blood phlebotomy is a relatively novel 
intervention in elective liver resection. Although it has now been utilized successfully in numerous patients, 
its efficacy and effectiveness have not been rigorously tested against the existing standard of care. The 
current state represents a rare opportunity to evaluate a new intervention in surgery before it is widely 
disseminated and adopted. Moreover, it is particularly important to test this intervention using a randomized 
controlled trial, as numerous other co-interventions exist to decrease blood loss and blood transfusion, thus 
potentially confounding any non-randomized study that seeks to examine this topic. 
 
What are the principal research questions to be addressed? The primary research objective is to 
determine whether the use of phlebotomy compared with standard of care prior to liver resection leads to 
decreased operative blood loss. Secondary objectives are to determine whether phlebotomy leads to 1) 
decreased blood product transfusion, 2) decreased perioperative morbidity, and 3) easier liver parenchymal 

 
 
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transection. The safety of phlebotomy (adverse events) will also be studied, as will be the feasibility of the 
current trial in terms of enrolment, protocol administration and study coordination. 
1.2 
Objectives and Outcome Measures 
Primary Objective: To determine whether the use of phlebotomy compared with standard of care prior to 
liver resection leads to decreased intraoperative blood loss, and to determine trial feasibility 
 
Secondary Objectives: (1) To determine whether phlebotomy leads to decreased blood product transfusion, 
(2) To determine whether phlebotomy leads to decreased perioperative morbidity, (3) To determine the 
safety of phlebotomy compared to standard of care, (4) To determine whether phlebotomy leads to easier 
liver parenchymal transection. 
1.3 
Trial Design 
This work proposes a proof of principle randomized controlled trial, using a conventional two-armed 
parallel design. One half of participants will be randomly allocated to the intervention (phlebotomy + 
standard practice), while the other half will be allocated to the control (standard practice). Consecutive 
patients will be randomized (1:1 allocation ratio) to the two study arms, with stratification by surgeon and 
indication. 
Intraoperative phlebotomy is a short-term intervention. All relevant data to be collected after surgery 
will be available within 30 days of the operation. As such, all data will be collected while the patient remains 
admitted in hospital, as well as at the postoperative clinic visits. For patients who return to the clinic before 
30 days from the surgery and for whom no further follow-up is required, the study coordinator will carry out 
one follow-up phone call to the patient at the 30-day point. No further follow-up will be required after 30 
days. 
2 
Methods: Participants, Intervention, and Outcomes 
2.1 
Study Setting 
The study will take place at the Ottawa Hospital, an academic hospital in Canada.  
2.2 
Eligibility Criteria 
Any patient being considered for a major elective liver resection will be considered for trial 
enrollment. Patients considered for a posterior right lobe or central resection will also be considered. 
Patients who are undergoing a concurrent additional abdominal or thoracic procedure (e.g. colonic 
resection) will also be included. 
Inclusion criteria: 
 
Participant is willing and able to give informed consent for participation in the study. 
 
Male or female, aged 18 years or above. 
 
Any patient being considered for a major elective liver resection (3 or more liver segments being 
operated upon) 
 
Any patient being considered for central resection of the liver (segments 4b and 5) 
 
Any patient being considered for posterior right lobe resection of the liver (segments 6 and 7) 
 
Exclusion criteria: The participant may not enter the study if any of the following apply: 
 Age <18 years 
 Pregnancy 
 Refusal of blood products 
 Active cardiac conditions  
 Unstable coronary syndromes 
 Decompensated HF (NYHA functional class IV; worsening or new-onset HF) 
 Significant arrhythmias 
 Severe valvular disease 
 
History of significant cerebrovascular disease 
 
Renal dysfunction (patients with an estimated GFR <60 mL/min) 
 
Abnormal coagulation parameters (INR >1.5 not on warfarin and/or platelets count <100 X109/L ) 
 
Evidence of hepatic metabolic disorder (bilirubin >35 mol/L) 
 
Presence of active infection 
 
Preoperative autologous blood donation 
 
Hemoglobin <100g/L 

 
 
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2.3 
Interventions 
Procedures for all patients: One to two days prior to surgery, Transfusion Medicine will be notified of the 
upcoming procedure. The patient’s name and medical record number (MRN) will be provided, together with 
a request for the number of collection bags based on the patient’s weight. Patients enrolled in the trial will 
be brought to the operating room where the surgical, nursing, and anesthesiology team will prepare the 
patient for surgery in the usual fashion. An arterial line, as well as a central venous catheter, will be 
inserted, in accordance with the standard of care in liver surgery. A non-invasive cardiac index monitor may 
be utilized, at the anesthesiologist’s discretion. Anesthesiologists involved in the trial will be assigned to 
patients included in the study by the anesthesia office. The anesthesiologist will prepare the patient for 
phlebotomy, irrespective of trial allocation – which will only be revealed to the anesthesiologist once the 
surgery is under way.  
 
Control arm: Patients randomized to standard practice will receive the intervention deemed to be 
consistent with the standard of care in the field. 
 
An epidural catheter will be inserted unless thought to be contraindicated by the anesthesiologist or refused 
by the patient. The epidural catheter will be used as part of the anesthesia management throughout the 
case, as is standard. Drugs infused in the epidural catheter will include both a narcotic agent, and a local 
anesthetic. A central venous catheter will be inserted. 
 
The mainstay of management in standard practice should be to achieve a low CVP (5 cm H20) 
throughout the liver parenchymal transection portion of the procedure. The methods used to achieve a low 
CVP (minimization of intravenous fluids, hypoventilation, diuretics, vasodilators, etc.) will be at the 
anesthesiologist’s discretion. Following the completion of the parenchymal transection, the surgeon will 
indicate this to the anesthesiologist, who will then have the opportunity to administer additional intravenous 
fluids if judged necessary. If at any point during the procedure, the anesthesiologist judges that the 
maintenance of a low CVP becomes unsafe for the patient, he/she will take steps in accordance with 
standard practice to rectify the situation. 
 
Intervention arm: For patients randomized to phlebotomy, the intervention will consist of the standard of 
care, plus whole blood phlebotomy.  
The attending anesthesiologist will carry out the intervention. Phlebotomy will consist of the withdrawal of 7-
10 mL/kg of whole blood from the patient, as tolerated, (e.g. for a patient weighing 70kg, 490 to 700 mL of 
whole blood). A range of volumes is provided, so as to allow the anesthesiologist some leeway in managing 
the hemodynamic effects of the intervention.  
 
Phlebotomy will be carried out using one of several vascular access options. Strict aseptic 
technique will be maintained, including proper swabbing of all ports, closing and sealing the system to 
prevent backflow of air or other potential contaminants into the line, and ensuring that the collection tubing 
is clamped twice before disconnecting it from the vascular access. 
 
A scale will be used to collect up to the desired weight. Assuming a desired phlebotomy of 450 mL 
(ie. one collection bag of whole blood), then 450 g of blood will be measured on the scale. Given that the 
specific gravity of whole blood at 37 C is known to be 1.0506 [37], the anesthesiologist will record the 
weight of blood withdrawn and will then back-calculate the true volume for patient care purposes. 
 
The phlebotomy should be interrupted if the patient experiences a drop in arterial blood pressure of 
more than 20%, despite the administration of vasopressors. Similarly, the phlebotomy should be interrupted 
if the anesthesiologist judges that it is best for the patient to do so. 
 
Following phlebotomy, the volume of removed blood should not be replaced by the administration of 
intravenous fluids; however, the volume of IV fluid administered during surgery be measured. In addition, 
the anesthesiologist should aim to keep the CVP low (5 cm H20) for the duration of the hepatic resection 
procedure, as is standard practice in liver surgery. 
 
In the case of patients requiring combined resections (eg. liver and colon), the liver resection portion 
of the procedure will always be conducted first so as to avoid any potential hemodynamics or regional 
blood flow issues for the colonic resection. Once the surgeon indicates that the parenchymal transection 
portion of the liver resection is completed, the anesthesiologist should transfuse the phlebotomized whole 
blood back into the patient, using standard transfusion precautions.  
 
In the event that the patient should require an unplanned transfusion of packed red blood cells or 
fresh frozen plasma during the parenchymal transection portion of the operation, the anesthesiologist 
should first administer the phlebotomized whole blood and then carry on with allogeneic blood products, at 
his/her discretion. 
 
Normally the collected blood is transfused back regardless of blood loss. Collected blood should be 
transfused in the operating room and not transported elsewhere. Collected blood must be transfused within 

 
 
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eight hours if kept in a cooler, or four hours if kept at room temperature. Any unused collected blood will be 
returned to Transfusion Medicine, where it will be discarded. All supplies must be returned to Transfusion 
Medicine at the end of surgery. 
 
The following technical steps will take place for patients randomized to phlebotomy: 
 
Supplies: 
 
Transfusion Medicine will send the requested number of whole blood collection bags labeller with 
the patient’s name and MRN and several plastic clamps in a Styrofoam cooler. 
 
The label must be checked using the standard protocol for checking all blood products. 
 
Plastic blue tubing clamps and a digital scale are available from the operating room. 
 
Selection of vascular access: 
 
Vascular access options, in suggested order of preference: 
 A 14-gauge antecubital IV (or other large proximal vein/IV caliber). Collection time for a unit 
is 5-10 minutes by this route 
 The 16-gauge port of a triple lumen central venous catheter (CVC). The CVC must have 
been inserted on the day of collection. Collection time is 20-30 minutes. 
 
Collection of blood: 
 
Attempts should be made to time the start of collection such that phlebotomy is complete shortly 
before start of the hepatic resection stage. 
 
Strict aseptic technique with proper swabbing of all ports is required. 
 
The system must remain closed/sealed to prevent backflow of air or other potential contaminants 
into the line. Ensure the collection tubing is clamped twice before disconnecting from the vascular 
access. 
 
Place a green towel on the floor and a weigh scale on the towel. Place the bag on the scale and 
weigh it and record the empty weight (usually about 75-85g). 
 
Determine a target or maximum including the empty bag weight. The volume of whole blood to be 
removed is 7-10 mL per kg of body weight, as tolerated. 
 
With all options it is important to maintain flow in order to prevent clotting in the catheter or tubing.  
 
Using an antecubital IV: 
 
Place a blue clamp on the collection tubing close to the needle. 
 
Remove the cap from the needle and place needle into saline locked IV. 
 
Unclamp to start the collection. 
 
Monitor the weight of the collected blood and collect up to 400 additional grams of blood in a bag. 
 
If necessary, raise the operating table and place the patient in Trendelenburg position as tolerated 
to increase venous pressure and the siphon effect. 
 
Frequently and gently agitate the bag to facilitate mixture of the blood with the CPDA anticoagulant. 
 
Additional steps if using a triple lumen CVC: 
 
Attach a stopcock to the brown hub of the CVC. 
 
Attach an Interlink Injection Site (“saline lock”) to the stopcock. 
 
Place a green towel on the pillow next to the CVC. 
 
Insert the venipuncture needle of the collection tubing directly into the saline lock. 
 
Carefully tape the CVC tubing and the collection tubing to the green towel, so that the needle does 
not disconnect. 
 
Using a stopcock and sideport syringe can traumatize red blood cells and should only be used to 
restart flow if other techniques to maintain flow do not work. 
 
It is frequently necessary to increase flow and prevent clotting by using a clamp to gently “strip” or 
milk the tubing and push the blood along. 
 
Completion of collection: (figure 2) 
 
Clamp the collection line near the needle and disconnect it from the vascular access.  
 
Place the bag on a Mayo stand.  
 
Cut the venipuncture needle off and dispose it in the sharps container.  
 
Tie two knots in the tubing, one next to the clamp and one near the bag. 

 
 
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 
You can also cut the line near the bag as long as there is at least one knot and one clamp between 
the cut and the bag.  
 
Decontaminate the scissors and the Mayo stand using a peroxide-based product (eg. Virox). 
 
Place the bag in the cooler. 
 
Collected blood must be transfused within eight hours if kept in a cooler, or four hours if kept at 
room temperature. 
 
 
Figure 2. Filled collection bag on scale, needle capped and clamped 
 
 
Fluid management: 
 
For phlebotomy without hemodilution, the collected blood is not replaced with crystalloid or colloid 
(this is different from acute normovolemic hemodilution). 
 
Normally the collected blood is autotransfused back regardless of the blood loss. Collected blood 
should be transfused in the OR and not transported elsewhere.  
 
Otherwise it must be returned to Transfusion Medicine and discarded. All supplies must be returned 
to Transfusion Medicine.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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2.4 
Outcomes and Timeline 
Outcome Measures 
Time-points of 
evaluation 
Three methods will be used independently. In the operating 
room, all blood and fluid aspirated from the abdomen will be 
measured accurately using graduated suction containers. 
The amount of irrigation fluid will be carefully monitored and 
recorded. The weight of all surgical sponges will be 
measured. This information will be used by 1) the surgeon 
and 2) anesthesiologist to independently visually estimate 
blood loss, as is commonly done in clinical practice. In 
parallel, intraoperative blood loss will also be 3) calculated 
based on the Flordal equation, using preoperative and day 2 
hemoglobin levels. 
Day 0 
 
Day 2 
Feasibility outcomes (compliance with the interventions, 
randomization procedures, time to achieve enrollment, 
blinding procedures, as well as the generation of data for a 
larger trial addressing blood transfusion) 
Various time 
points 
Outcome Measures 
Timepoints of 
evaluation 
Blood product transfusion rate (packed red blood cells, fresh 
frozen plasma, cryoprecipitate, albumin, others) 
 
 
 
 
Day 7 
 
Day 30 
 
 
Overall morbidity rate and serious morbidity rate (Dindo-
Clavien grade 3a or greater) (Appendix 1) 
Day 30 
Perioperative overall morbidity, mortality, and adverse 
events 
Day 7 
Surgeon perception scale (Appendix 2) 
Day 0 
 
2.5 
Sample Size 
Based on internal data obtained at the study center in 2011-2012, the mean intraoperative blood 
loss in major liver resections is 777 ± 547 mL (n=21). With phlebotomy, the median blood loss was 400 mL 
[39]. Assuming a reduction in mean blood loss with phlebotomy from 775 mL to 400 mL (standard deviation 
500 mL), one requires 56 patients to achieve 80% power and 5% alpha error. Assuming that the surgical 
plan for liver resection would be abandoned in 10% of patients after randomization [40], one would require 
randomization of 62 patients. 
 
2.6 
Recruitment 

 
 
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Patients of the Liver and Pancreas Unit will be considered for enrollment. All patients being considered for 
elective liver resection will be seen by an attending surgeon in the outpatient clinic.  
3 
Methods:  Assignment of Interventions 
3.1 
Allocation 
Consecutive patients will be randomized in a 1:1 (phlebotomy + standard practice, or just standard 
practice) allocation ratio to the two arms of the study, with stratification by indication for resection and the 
use of permuted blocks of variable length (2, 4, and 6). The randomization scheme will be created using 
sealedenvelopes.com by the study coordinator; the PI will be blinded. Verification of eligibility will be done 
by the surgeons in clinic, and managed by the coordinator prior to randomization. The randomization 
sequence will then be placed in a sealed double-opaque envelope to be given to the anesthesiologist the 
morning of the participant’s surgery. Enrolled patients will be randomized once surgery is underway and the 
surgeon confirms that a major liver resection will in fact take place. Randomization will thus be in effect and 
the allocation will be revealed to the anesthesiologist, who will carry out the intervention or control arm, as 
appropriate. 
3.2 
 Blinding 
The patient will be blinded to the intervention, as allocation will be revealed following induction of 
general anesthesia. The anesthesiologist, operating room nurses, and study coordinator will not be blinded 
to the intervention, as this is clearly impractical in this setting.  
 
The surgeon will be blinded to the intervention. Blinding of the surgeon will be completed by 
carrying out all physical steps necessary for phlebotomy for both treatment arms, including placing patient 
in Trendelenburg position, lifting the bed up, preparing the necessary IV tubing, and connecting the IV 
tubing to the CVC or peripheral IV. Furthermore, all equipment necessary for phlebotomy will be set up 
before revealing the trial allocation and the actual blood collection will take place behind large sterile drapes 
in order to maintain blindness.  Following completion of the phlebotomy, the collection bag will be placed 
within a Canadian Blood Services transfusion card box and kept in the operating room. At the time of auto-
transfusion of the whole blood, the collection bag and tubing will be wrapped in opaque green towels, so as 
to prevent the surgeon from knowing what is being given. In the case of randomization to the standard of 
care, a plain saline bag will be hooked up and wrapped in green towels in a similar fashion.  
 
All operating room personnel will be instructed prior to the onset of surgery to maintain blindness for 
the surgeon and to not openly discuss the intervention. Large signs will be posted on the operating room 
doors leading in and out of the operating room so as to avoid discussing openly the intervention at times of 
shift change or turnover in nursing personnel. Blinding of the surgeon will constitute an element of feasibility 
that is being tested in this trial. 
The anesthesiologist time will not be blinded. In the event that the patient should require a blood 
transfusion during the liver resection, the anesthesiologist will proceed to transfuse the phlebotomized 
blood (phlebotomy arm) or allogeneic packed red blood cells (standard practice arm) at the time where 
he/she judges to be the most clinically appropriate and in accordance with the study transfusion protocol. 
For the first unit transfused, the whole blood collection bag or unit of allogeneic packed red blood cell would 
be concealed from the surgeon by wrapping it in a green towel. Any subsequently transfused units of 
allogeneic packed red blood cells would not be required to be wrapped in a green towel, as these units 
would be in addition to the autologous blood or the first allogeneic unit, thus maintaining blinding. At any 
time during the study, the attending anesthesiologist can choose to unblind the surgeon for patient safety 
reasons. 
4 
Data Collection, Management, and Analysis 
4.1 
Data Collection Methods 
Case report forms (CRFs) were created in collaboration with the surgical and anesthesiology teams 
to ensure that all relevant data would be collected. These CRFs consist of 1) Demographics and medical 
history details, 2) Intraoperative details – Surgeon, 3) Intraoperative details – Anesthesiologist, and 4) 
Postoperative details. Moreover they contain some source data. 
The following points are source documents in the Intraoperative details – Surgeon CRF: 
 
7. Liver appearance  

 
 
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11. Who did the transection? 
12. Transection time 
13. EBL 
14. IF surgeon thinks phlebotomy was implemented  
15. Was blinding maintained? 
16. Surgical perception scale of how the surgery went. 
 
The following points are source documents in the Intraoperative details – Anesthesiologist CRF: 
 
7. Blood loss prior to parenchymal transection 
8. Hemoglobin levels 
9. Systolic blood pressure at start of resection 
10. Systolic blood pressure at end of resection 
11. Urine output (intraoperative) 
13. Start resection time 
14. End resection time 
15. Hemodynamics including: time, CVP and CI, SVV, U/O for different times in the surgery 
17. Target total volume for collection bags 
18. Target total blood weight  
19. Target weight of bag 1 
20. Target weight of bag 2 
21. Start weight of each bag, and the different times and weight of bag as it was filling 
23. Net weight of blood on sponges 
24. Volume in suction containers (use graduated container) 
25. Volume of irrigation fluid. 
26. Estimate of body fluids such as bile, ascites. 
27. Estimate of other blood loss (drapes, gowns, etc.) 
28. Anesthesiologist's estimate for EBL 
29. Was blinding maintained from surgeon?    
30. Was blinding maintained from fellow, if present?      
 
The following points are source documents in the Post-operative details CRF: 
13. Adverse Events and their grades: Adverse Events will be found in the electronic patient charts and will 
be graded on the Dindo-Clavien scale by the PI.  
The surgeon, anesthesiologist and study coordinator are responsible for completing different sections of the 
CRF. All parties will receive briefing on the content of the CRF to ensure that the forms are filled out in a 
consistent manner.   
4.2 
Data Management 
The study staff will ensure that the participants’ anonymity is maintained.  The participants will be 
identified only by a participant ID number on all study documents and any electronic database. For each 
study patient, relevant preoperative, intraoperative, and postoperative data will be collected by the study 
coordinator using the CRF (Appendix 4), and then entered into a password-protected database. The hard 
copies of the CRFs will be kept in a locked and secure drawer in the Liver and Pancreas Unit of The 
Ottawa Hospital by the study coordinator. 
4.3 
Statistical Methods 
Three different intraoperative blood loss measurements will be used for analysis. Measurements will 
be taken from: a) surgeon estimation, b) anesthesiologist estimation, and c) calculated measure of blood 
loss [38]. Each measure of blood loss will be reported separately, in addition to computing the mean of the 
three methods. The mean difference in blood loss between the two trial interventions will be compared 
using unpaired t tests with 95% confidence intervals.  
 
Continuous secondary outcomes will be examined using unpaired t tests, while dichotomous 
secondary outcomes will be reported using chi-square or Fisher’s tests, as appropriate.  
Primary, secondary, and feasibility outcomes will be analyzed after the last trial patient has been 
followed for 30 days. Safety data will be compiled by the study statistician in accordance with the trial 
Monitoring Plan and reviewed by a Data Safety and Monitoring Board. 

 
 
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The primary outcome of intraoperatobe blood loss will be compared based on indication for liver 
surgery (hepatocellular carcinoma or cholangiocarcinoma vs other malignant/benign indications) and based 
on other methods for blood loss prevention (inflow occlusion, tranexamic acid, CVP <5 cm H2O), while 
feasibility outcomes will be reported using descriptive statistics. 
 
5 
Methods: Monitoring 
5.1 
Data Monitoring 
The PI, co-investigators, and the study coordinator will comprise the trial Executive Committee. The 
Executive Committee will meet at least twice per year to review the trial progress. The PI, study 
coordinator, and the group of trial anesthesiologist will comprise trial Steering Committee. This committee 
will implement the study and aid in the review of all study procedures. The Steering Committee will meet at 
least twice per year to ensure the correct implementation of the study protocol. 
 
A trial Monitoring Plan will be created together with the OHRI Clinical Research Facilitator & 
Monitor. A Data Safety and Monitoring Board (DSMB) will also be appointed and will have full responsibility 
for one interim analysis for safety and monitoring of response variables for adverse events while the trial is 
ongoing. This committee will function independently from all other study committees and serve in an 
advisory role to the Executive and Steering committees. The DSMB will recommend termination or 
continuation of the trial based on interim analyses. 
5.2 
Harms  
The PI or co-investigator will determine if any serious and unexpected adverse events occur from 
randomization to post-op day 30. The study coordinator and PI, or co-investigator will examine changes in 
laboratory values, vital signs and clinical data and will determine if the changes are clinically important and 
different from what is expected during treatment of participants having undergone hepatic surgery and 
general anesthesia.  
5.2.1 Adverse Events 
As perioperative morbidity/complications represent an important secondary outcome in this trial, 
adverse events (AEs) will be carefully monitored and recorded. AEs can generally be described as any 
unfavorable and unintended sign, symptom or disease temporarily associated with the treatment, whether 
or not related to the study treatment.  
For the purpose of this trial, any surgical, medical, or anesthesia-related AE that deviates from the 
usual care of patients undergoing major liver resection will be considered. All such AEs will be collected 
and recorded in the study AE Source From by the PI and/or study coordinator. The PI will then assign a 
grading to this AE, based on the Dindo-Clavien classification of perioperative complications (Appendix 1).  
The following will thus not be considered AEs: 
a. Intraoperative: bleeding (unless deemed unusually severe by the PI), hypotension (unless deemed 
unresponsive to usual mitigation strategies), oliguria 
b.  Postoperative: pain, hypotension (unless deemed unresponsive to usual mitigation strategies), 
oliguria, nausea, vomiting, sore throat, confusion (unless deemed related to medication), muscle 
aches, pruritus, chills, chest pain (unless deemed to be related to a defined AE such as acute 
coronary syndrome, etc.), anemia not requiring a transfusion, electrolyte disturbances (unless they 
do not respond to usual replacement therapy) 
Any AE that is graded as Dindo-Clavien grade 3a or greater will be considered a severe adverse 
event (SAE). SAEs will be recorded on the study SAE Case Report Form (Appendix 5). All SAEs will be 
further assessed by the PI for expectedness and relatedness to the study procedures. On that basis, 
unexpected SAEs will be reported to the REB. 
5.3 
Auditing 
The study may be monitored or audited in accordance with the current approved protocol, GCP, and 
relevant regulations and standard operating procedures. 

 
 
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6 
Ethics and Dissemination 
6.1 
Research Ethics Approval 
The protocol, informed consent forms, and any other study material will be submitted to the OHSN-
REB for written approval. The Investigator will submit and, where necessary, obtain approval from the 
OHSN-REB for all substantial amendments to the original approved documents. 
The principal investigator will ensure that this study is conducted in accordance with relevant regulations 
and with Good Clinical Practice. 
6.2 
Protocol Amendments 
If any protocol amendment or modification takes place, approval from the REB will be obtained 
before implementing any change. Once REB approval is obtained, the PI will brief all relevant parties (i.e. 
surgeons, anesthesiologists). 
6.3 
Consent 
Once a decision is made to offer surgery to the patient, the attending surgeon will obtain written 
consent for the surgery. At this time, the patient will also be screened for eligibility based on the type of 
proposed resection, as well as any exclusion criteria. The Trial Eligibility Form will be filled and signed by 
the surgeon, whether or not a patient is enrolled (Appendix 3). The surgeon will introduce the study and will 
obtain verbal permission from the patient that the study coordinator can approach them to go over the 
consent form with them. Once the clinical encounter is completed, the study coordinator will meet or call the 
patient to explain the consent form and present the study in detail: the exact nature of the study; what it will 
involve for the participant; the implications and constraints of the protocol; the known side effects and any 
risks involved in taking part. It will be clearly stated that the participant is free to withdraw from the study at 
any time for any reason without prejudice to future care, without affecting their legal rights, and with no 
obligation to give the reason for withdrawal. In addition, sometimes it is possible that the study coordinator 
cannot meet with the potential trial participant at the time of their clinical assessment. If the study 
coordinator is unavailable but the patient meets the criteria for the trial, the surgeon will introduce the study 
and give a copy of the consent form for review to the patient. Once the clinical encounter is completed, the 
study coordinator will call the patient to review the consent form with them and present the study in detail, 
risks and benefits will be provided, and a verbal consent will be obtained. On the day of the patient’s 
preadmission appointment, the coordinator will meet with the patient and get written signed consent,  
 
The participant will be allowed as much time as wished to consider the information, and the 
opportunity to question the Investigator, their family physician or other independent parties to decide 
whether they will participate in the study. Written Informed Consent will then be obtained by means of 
participant dated signature and dated signature of the person who presented and obtained the Informed 
Consent.  A French version of the Consent Form will also be available at all times. 
6.4 
Participant Confidentiality  
The study staff will ensure that the participants’ anonymity is maintained.  The participants will be 
identified only by a participant ID number on all study documents and any electronic database. PHI and PII 
recorded for this study will include name, medical record number, medical history, test results, gender, and 
month/year of birth. PHI and PII will be maintained in a secure, password-protected, master study list 
accessible only to the investigators and the study coordinator. This file will be linked to other study 
documents, forms and databases by way of a unique study ID. The master study list will be maintained 
exclusively on Ottawa Hospital secure servers. All other study materials will be accessible only by study 
investigators and will be maintained on the Ottawa Hospital server. Computer access to these documents 
will be made from the HPB surgery office, a secure office environment within the Ottawa Hospital. Any data 
derived from the study and released to the DSMB or to the study statistician will be completely de-
identified. 
6.5 
Declaration of Interests 
There are no conflicts of interest to declare. 
6.6 
Access to Data 
 All collected forms will be computerized into a single dataset and delivered to the trial statistician at 
the Ottawa Hospital Research Institute Methods Centre. An interim analysis for safety will be carried out 
and presented to the DSBM. The data will be presented to the DSMB by the study coordinator. The primary 
investigator will not have access to these data until completion of the study. 

 
 
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6.7 
Ancillary and Post-trial Care 
There is no ancillary and post-trial care to report. 
6.8 
Dissemination Policy 
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases 
and any other publications arising from the study. Authors will acknowledge that the study was funded by a 
Canadian Surgical Research Fund grant. Authorship will be determined in accordance with the ICMJE 
guidelines and other contributors will be acknowledged. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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7 
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33. Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal RF, Roy A. Effect of low central venous pressure 
 
and phlebotomy on blood product transfusion requirements during liver transplantation. Liver Transpl 
 
2006;12:117-123 
34. Jarnagin WR, Gonen M, Maithel SK, Fong Y, D’Angelica MI, DeMatteo RP, et al. A prospective 
 
randomized trial of acute normovolemic hemodilution compared to standard intraoperative 
 
management in patients undergoing major hepatic surgery. Ann Surg 2008;248:360-369 
35. Dindo, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with 
 
evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205-213 
36. Segal JB, Basco-Colmenares E, Norris EJ, Guallar E. Preoperative acute normovolemic hemodilution: 
 
a meta-analysis. Transfusion 2004;44:632-644.  
37. Trudnowski RJ, Rico RC. Specific gravity of blood and plasma at  4 and 37 C. Clin Chem. 
 
1974;20:615-616. 
38. Flordal PA. Measurement of blood loss in clinical studies. Eur J Anaesthesiol Suppl 1997;14:35-37 
39. Rekman J, Wherrett C, Martel G. Phlebotomy resulting in controlled hypovolemia to prevent blood loss 
 
in major hepatic resections. Manuscript in preparation. 
40. Strasberg SM, Dehdashti F, Siegel BA, Drebin JA, Linehan D. Survival of patients evaluated by FDG-
 
PET before hepatic resection for metastatic colorectal carcinoma: a prospective database study. Ann 
 
Surg 2001;233:293-299. 
 
 

 
 
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8 
Appendices 
8.1 
 Appendix 1: Dindo-Clavien Classification of Surgical Complications [from 35] 
 
Grades 
Definition 
Grade 1 
Any deviation from the normal postoperative course without the need for pharmacological 
treatment or surgical, endoscopic and radiological interventions. 
Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgesics, diuretics 
and electrolytes and physiotherapy. This grade also includes wound infections opened at 
the bedside. 
Grade 2 
Requiring pharmacological treatment with drugs other than such allowed for grade I 
complications. Blood transfusions and total parenteral nutrition are also included. 
Grade 3 
Requiring surgical, endoscopic or radiological intervention 
3a 
Intervention not under general anesthesia 
3b 
Intervention under general anesthesia 
Grade 4 
Life-threatening complication (including CNS complications*), requiring IC/ICU-
management 
4a 
Single organ dysfunction (including dialysis) 
4b 
Multi organ dysfunction 
Grade 5 
Death of a patient 
*Brain hemorrhage, ischemic stroke, subarachnoid bleeding, but excluding transient ischemic attacks (TIA); 
IC: Intermediate care; ICU: Intensive care unit. 
 
 

 
 
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8.2 
 Appendix 2: PRICE trial surgeon perception scale 
 
PRICE TRIAL SURGEON PERCEPTION SCALE 
 
To be filled by the surgeon immediately following liver parenchymal transection 
 
Please rate the overall ease/difficulty with which this liver resection was completed: 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
Easiest 
 
 
 
Average  
 
 
 
Hardest 
 
 
Please rate the ease/difficulty with which the liver parenchymal transection was completed: 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
Easiest 
 
 
 
Average  
 
 
 
Hardest 
 
 
Please rate your impression of blood loss during the parenchymal transection: 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
None/minimal 
 
 
Average  
 
 
 
Most/excessive 
 
 
Please rate your impression of the filling status of the hepatic veins during the parenchymal transection: 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
Empty/flat 
 
 
Average  
 
 
 
Full/excessive 
 
 
 
 
 
 
 
 
 
Surgeon signature: ___________________________________________________ 
 
 
 
 
Date: _______________________________________________________________ 
 
 

 
 
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8.3 
Appendix 3: PRICE trial eligibility form 
 
PRICE TRIAL ELIGIBILITY FORM 
 
 
To be filled by the surgeon who consents the patient for any liver surgery 
 
Each of criteria must be fulfilled: 
 
 The patient is able to give informed consent for participation in the study. 
 
 The patient is aged 18 years or above. 
 
 The patient has been consented for an elective major liver resection (3 or more liver segments being 
operated upon). 
 
 
None of the following exclusion criteria can be present: 
 
Exclusion Criteria  
Circle Y/N, add values and date 
where needed  
Sign off (initials) 
The 
patient 
has 
been 
consented for 
an 
elective 
minor liver resection (less 
than 3 liver segments being 
operated upon). 
 
 
            Y            /              N 
              
 
                        --- 
 
Age <18 years 
 
  
          Y            /            N 
 
 
                        --- 
 
Pregnancy 
 
          Y            /            N 
 
 
                        --- 
Refusal of blood products 
 
         Y            /            N 
 
           
                        --- 
 
Active cardiac conditions  
 Unstable 
coronary 
syndromes 
 Decompensated 
HF 
(NYHA functional class 
IV; worsening or new-
onset HF) 
 Significant arrhythmias 
 Severe 
valvular 
disease 
 
 
 
 
 
         Y            /            N 
              
 
 
 
 
                        --- 
 
History 
of 
significant 
cerebrovascular disease 
          
        Y            /             N 
 
              
                        --- 
 
Presence of active infection 
 
        Y            /              N 
 
              
                        --- 
 
Preoperative 
autologous 
blood donation 
 
          Y            /             N 
 
              
                        --- 
 
Renal dysfunction (patients 
with an estimated GFR <60 
 
GFR: _______________ 
 

 
 
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mL/min) 
 
Date 
of 
blood 
collection: 
________________________ 
 
Abnormal 
coagulation 
parameters (INR >1.5 not on 
warfarin and/or platelets count 
<100 X109/L ) 
 
INR: _________________ 
 
Date 
of 
blood 
collection: 
_____________________ 
 
Platelet count: ____________ 
 
Date 
of 
blood 
collection: 
_______________________ 
 
 
Evidence of hepatic metabolic 
disorder (bilirubin >35 mol/L) 
 
Bilirubin: _____________ 
 
Date 
of 
blood 
collection: 
____________________ 
 
 
Hemoglobin <100 g/L 
 
Hemoglobin: _____________ 
 
Date 
of 
blood 
collection: 
_______________________ 
 
 
 
 
Surgeon signature: ___________________________________________________ 
 
 
Date: _______________________________________________________________ 
 
 
 
 

 
 
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8.4 
 Appendix 4: PRICE trial Case Report Forms (CRFs) and source documentation 
 
Demographics and medical history details 
1. Date of birth (month/year): 
_______________________________________________ 
 
2. Gender              m            /              f 
 
3. Comorbidities (please check all that apply) 
 
Current smoker 
 Number of pack years __________ 
Former smoker 
 Number of pack years __________ 
 
 Years since quitting ____________ 
 
Never smoked 
 
 Myocardial infarction (history, not 
ECG changes only) 
 
 Diabetes mellitus without complication 
(excludes diet controlled alone) 
 Congestive heart failure 
 Diabetes with end-organ damage 
(retinopathy, neuropathy, nephropathy, 
brittle diabetes) 
 
 Peripheral vascular disease (incl. AAA 
≥6 cm) 
 Moderate/severe renal disease 
 
 Cerebrovascular accident (CVA with 
mild or no residua or TIA) 
 
 
 Malignant neoplasm without metastasis 
(exclude if >5 years from diagnosis) 
 Hemiplegia 
 
 Metastatic solid tumor 
 Dementia 
 
 
 Leukemia (acute or chronic) 
 COPD 
 
 Lymphoma 
 Rheumatologic disease 
 
 AIDS (exclude if only HIV positive) 
 Peptic ulcer disease 
 
 Hepatitis B  
 Mild liver disease (no portal 
hypertension, incl. chronic hepatitis)  
 
 Hepatitis C 
 Moderate/severe liver disease 
 Cirrhosis 
 
 
 Other underlying liver disease  
 
_______________________________ 
 

 
 
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 Other   
 
________________________________ 
 
 
 
4. Previous abdominal surgeries (please list):_____________________________________ 
_______________________________________________________________________ 
5. Previous liver surgeries: ___________________________________________________ 
_______________________________________________________________________ 
 
6. Weight: _________kg       and height: ________cm 
 
7. Pre-operative weight loss (please provide numerical value and indicate units): 
 
_____________________________________ 
 
 
8. History of jaundice   
 Yes   
 
No 
 
9. History of cholangitis  
 Yes 
 
 
No 
 
10. Biliary drainage: 
 
 Yes  
 No 
 
 
 
 
 
 Stent 
 PTC 
 
  
 
 
Date of first drainage: _________________________________ 
 
11. Preoperative chemotherapy (within 6 months of surgery):         y             /             n 
 
If yes, which type (and number of cycles): __________________________________  
 
____________________________________________________________________ 
 
12. Preoperative PV embolization:            y             /             n 
13. Intrabiliary stent placement:           y             /                n      
 
Date of intrabiliary stent placement: __________________________________ 
 
Method of intrabiliary stent placement:  
 
ERCP  
 
PTC 
14. Preoperative laboratory studies (within 90 days of surgery) 

 
 
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Blood work 
Blood work results 
Date of blood work 
Hemoglobin (g/L) 
 
 
INR 
 
 
Platelet (x109/L) 
 
 
Total bilirubin (umol/L) 
 
 
Neutrophils (x109/L) 
 
 
Lymphocytes (x109/L) 
 
 
Albumin (g/L) 
 
 
AST (U/L) 
 
 
ALT (U/L) 
 
 
GGT (U/L) 
 
 
ALP (U/L) 
 
 
Creatinine (umol/L) 
 
 
CA19-9 (U/L) 
 
 
CEA (ug/L) 
 
 
AFP (ug/L) 
 
 
Intraoperative details – Surgeon 
1. Surgeon: ______________________________________________ 
 
2. Hepatobiliary fellow present:           y                /               n 
 
3. Resident present:              y                /               n 
 
4. Main liver procedure  
 
 Right hepatectomy  
 Right extended hepatectomy 
 Left hepatectomy 
 Left extended hepatectomy 
 En bloc caudate resections 

 
 
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 Segmental resection 
Description: __________________________________________ 
5. Extrahepatic procedures: ____________________________________________ 
 
6. Number of segments resected:       2           3             4            5               6           
 
7. Liver appearance  
 Normal 
 Blue 
 Fatty 
 Cirrhosis 
 Other: _________________________________ 
 
 
8. Transection technique(s): 
 Crush-clamp 
 Water jet 
 Thunder beat 
 Ligature 
 harmonic 
 Staple 
 Hemopatch 
 Surgicel 
 Floseal   
 Argon 
 Tachosil 
 Cautery  
9. In flow control: 
 
 Intrahepatic transection  

 
 
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 Extrahepatic transection  
10. Pringle:      y                /               n 
 IF yes:   
 Intermittent  
 Continuous 
 Total time (min): ________________________  
 
 
11. Who did the transection: 
 Surgeon 
 2 surgeons 
 Surgeon + fellow 
 Surgeon + resident 
12. Transection time (min) ________________________ 
13. EBL (ml): __________________________________ 
 
14. Do you think phlebotomy was implemented?             y                     /                n 
 
15. Was blinding maintained?            y                   /                    n 
 
 
16. SURGEON PERCEPTION SCALE: 
(To be filled by the surgeon immediately following liver parenchymal 
transection) 
Please rate the overall ease/difficulty with which this liver resection was 
completed: 
1       2       3       4       5       6       7       8       9       10 
  
Easiest                        Average                        Hardest 
  
  
Please rate the ease/difficulty with which the liver parenchymal transection was 
completed: 
1       2       3       4       5       6       7       8       9       10 
Easiest                        Average                        Hardest 
  
  
Please rate your impression of blood loss during the parenchymal transection: 
1       2       3       4       5       6       7       8       9       10 
  
None/minimal                Average          Most/excessive 
  
  

 
 
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Please rate your impression of the filling status of the hepatic veins during the parenchymal 
transection: 
1       2       3       4       5       6       7       8       9       10 
  
Empty/flat                 Average                 Full/excessive   
  
  
Surgeon Signature: _______________ 
 
Intraoperative details – Anesthesiologist 
1. Anesthesiologist: _________________________________________ 
 
2. Blood volume removed (ml) _____________________ 
3. ASA classification  
 
 I – Healthy patient 
 
 II – Mild systemic disease, no functional limitation 
 
 III – Severe systemic disease, definite functional limitation 
 
 IV – Severe systemic disease, constant threat to life 
 
 V – Moribund patient, not expected to survive 
 
 E – Emergency situation 
4. Intraoperative fluid given 
Crytalloid (ml) _____________________ 
Colloid (ml) _______________________ 
5. Pressors given:           y                   /                 n 
a) If yes, type and total dose: _____________________________________ 
 
6. Epidural:            y                   /                  n 
a) If yes, list drugs: ____________________________________________ 
 
7. Blood loss prior to parenchymal transection: _____________________ 
8. Hemoglobin level ___________________________ 
9. Systolic blood pressure at start of resection _____________________ 
10. Systolic blood pressure at the end of resection ____________________ 

 
 
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11. Urine output (intraoperative, ml) _____________________ 
12. Transfusion of blood products (circle one)         y                 /                n 
 
If yes, please specify product and number of units: 
 
 Packed RBC: ______________ 
 FFP: ________________ 
 Platelets: ______________ 
 Albumin: _______________ 
13.  Start resection: _____________________________________ 
14. End resection: ______________________________________ 
 
 
15. HEMODYNAMICS: 
Time 
CVP 
CI 
SVV 
U/O 
(Cumul.) 
Pre-Incision: 
  
  
  
  
  
30-60 min post incision: 
  
  
  
  
  
Pre Phlebotomy: 
  
  
  
  
  
Post Phlebotomy/Pre-
Resection: 
  
  
  
  
  
Post resection: 
  
  
  
  
  
Post transfusion/Fluid bolus   
  
  
  
  
Start Wound Closure: 
  
  
  
  
  
 
 
16. Patient weight: _______________________ 
17. Target total volume (7-10 
mL/kg) 
  
18. Target total blood weight 
  
Weight = Vol. x Spec. Gravity (1.0506) 
19. Target weight Bag #1 (Max 
473g) 
  
Note 450 mL = 473g 
20. Target blood weight Bag #2 
  
 
 
 
21.  
Bag #1 
Bag #2 
Starting Wt. 
  
Starting Wt. 
  
Target Wt. 
  
Target Wt. 
  

 
 
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Time 
Weight 
Time 
Weight 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
  
 
 
 
 
 
  
 
  
  
  
  
 
22. Start Transection time: _______   CVP: _____   Cl: _____   SVV: ______   U/O: ______ 
 
Estimated Blood Loss at end of case: 
  
 
23. Net weight of blood on sponges 
  
24. Volume in suction containers (use graduated 
container) 
  
25. Volume of irrigation fluid. 
  
26.Estimate of body fluids such as bile, 
ascites. 
  
27. Estimate of other blood loss (drapes, gowns etc.) 
  
28. Anesthesiologist's estimate: 
  
29. Was blinding maintained from surgeon?                  y                     /                       n 
30. Was blinding maintained from Fellow?                    y                     /                       n 
31. Net EBL: ___________________________ 
Anesthesiologist Signature: _____________________________________ 
 
 
 

 
 
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Postoperative details 
1. Immediate postop (PACU) lab results: 
a. Hemoglobin (g/L): ____________________________ 
b. Platelet count (x109/L): _________________________ 
c. INR: ________________________________________ 
d. Creatinine (umol/L): ___________________________________ 
e. Bilirubin (umol/L): ____________________________________  
f. AST (U/L): ________________________________________ 
g. ALT (U/L): ________________________________________ 
h. PO4 _____________________________________________ 
 
2. POPD #: _________________________________________ 
a. Hemoglobin (g/L): ____________________________ 
b. Platelet count (x109/L): _________________________ 
c. INR: ________________________________________ 
d. Creatinine (umol/L): ___________________________________ 
e. Bilirubin (umol/L): ____________________________________  
f. AST (U/L): ________________________________________ 
g. ALT (U/L): ________________________________________ 
h. PO4 _____________________________________________ 
 
3. POPD #: _________________________________________ 
a. Hemoglobin (g/L): ____________________________ 
b. Platelet count (x109/L): _________________________ 
c. INR: ________________________________________ 
d. Creatinine (umol/L): ___________________________________ 
e. Bilirubin (umol/L): ____________________________________  

 
 
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f. AST (U/L): ________________________________________ 
g. ALT (U/L): ________________________________________ 
h. PO4 _____________________________________________ 
 
4. POPD #: _________________________________________ 
a. Hemoglobin (g/L): ____________________________ 
b. Platelet count (x109/L): _________________________ 
c. INR: ________________________________________ 
d. Creatinine (umol/L): ___________________________________ 
e. Bilirubin (umol/L): ____________________________________  
f. AST (U/L): ________________________________________ 
g. ALT (U/L): ________________________________________ 
h. PO4 _____________________________________________ 
 
5. POPD #: _________________________________________ 
a. Hemoglobin (g/L): ____________________________ 
b. Platelet count (x109/L): _________________________ 
c. INR: ________________________________________ 
d. Creatinine (umol/L): ___________________________________ 
e. Bilirubin (umol/L): ____________________________________  
f. AST (U/L): ________________________________________ 
g. ALT (U/L): ________________________________________ 
h. PO4 _____________________________________________ 
 
 

 
 
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6. POPD #: _________________________________________ 
a. Hemoglobin (g/L): ____________________________ 
b. Platelet count (x109/L): _________________________ 
c. INR: ________________________________________ 
d. Creatinine (umol/L): ___________________________________ 
e. Bilirubin (umol/L): ____________________________________  
f. AST (U/L): ________________________________________ 
g. ALT (U/L): ________________________________________ 
h. PO4 _____________________________________________ 
 
7. POPD #: _________________________________________ 
a. Hemoglobin (g/L): ____________________________ 
b. Platelet count (x109/L): _________________________ 
c. INR: ________________________________________ 
d. Creatinine (umol/L): ___________________________________ 
e. Bilirubin (umol/L): ____________________________________  
f. AST (U/L): ________________________________________ 
g. ALT (U/L): ________________________________________ 
h. PO4 ____________________________________________ 
 
8. POPD #: _________________________________________ 
a. Hemoglobin (g/L): ____________________________ 
b. Platelet count (x109/L): _________________________ 
c. INR: ________________________________________ 
d. Creatinine (umol/L): ___________________________________ 
e. Bilirubin (umol/L): ____________________________________  

 
 
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f. AST (U/L): ________________________________________ 
g. ALT (U/L): ________________________________________ 
h. PO4 _____________________________________________ 
 
 
9. Length of stay (d) ___________________________ 
 
10. Post-operative transfusion of blood products (circle one)           y            /           n   
 
 
11. POD# __________________________ 
 
o If yes, please specify product and number of units: 
 Packed RBC: ______________ 
 FFP: ________________ 
 Platelets: ______________ 
 Albumin: _______________ 
 
_________________________________ 
 
________________________               
 
        RC signature 
 
 
 
     
 
Date  
 
**The rest of this form is to be completed by a surgeon 
       12. Diagnosis 
 
 Metastatic colorectal  
 Metastatic other (specify) 
 HCC 
 Biliary cancer 
 Other: ____________________________ 
 
 

 
 
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       13. List all adverse events and their grade:   
Adverse Event 
Grade 
MD initial  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Full Scale 
Grades 
Definition 
Grade  I: 
Any deviation from the normal postoperative course without the need for 
pharmacological treatment or surgical, endoscopic and radiological 
interventions. 
Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, 
analgetics, diuretics and electrolytes and physiotherapy. This grade also 
includes wound infections opened at the bedside. 
Grade  II: 
Requiring pharmacological treatment with drugs other than such allowed 
for grade I complications. 
Blood transfusions and total parenteral nutrition are also included. 
Grade  III: Requiring surgical, endoscopic or radiological intervention 
Grade III-a: intervention not under general anesthesia 
Grade III-b: intervention under general anesthesia 
Grade IV: 
Life-threatening complication (including CNS complications)‡ requiring 
IC/ICU-management 
Grade IV-a: single organ dysfunction (including dialysis) 
Grade IV-b: multi organ dysfunction 
Grade V: 
Death of a patient 
 
14. Liver pathology (nontumour) 
 Normal 
 Cirrhosis/fibrosis  
 Steatosis/steatohepatitis  
 Other (specify): ________________________________ 
 
 
_________________________________ 
 
________________________                      
Surgeon signature 
 
 
 
    Date (dd/mm/yyyy)  
 

 
 
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8.5 
Appendix 5: Adverse Event/Serious Adverse Event Case Report Form 
 
 
Adverse Event/Serious Adverse Event Case Report Form 
“The PRICE Trial: Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major hepatic resections” 
AE/SAE 
# 
Description 
Start Date 
End 
Date/Ongoing 
Date Site 
Became 
Aware 
Grade  
Serious 
(Y/N)  
Expected 
(Y/N) 
Attribution 
Outcome 
MD Initials 
& Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Grade 
Attribution 
Outcome 
1 – Mild 
0 - Definite 
0 - Fatal 
2 – Moderate 
1 - Probable 
1 – Not recovered/not resolved 
3 – Severe 
2 - Possible 
2 – Recovered w/sequelae 
4 – Life Threatening 
3 - Unlikely 
3 – Recovered w/o sequelae 
5 – Death (Fatal) 
4 - Unrelated 
4 – Recovering/Resolving 
 
Participant ID # ______________________ 
 
Page ____________of________________ 

 
 
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8.6 
Appendix 6: Informed consent, English and French 
 
 
     
                           
                              
 
 
 
PARTICIPANT INFORMED CONSENT FORM 
 
 
Title of Study: The PRICE Trial: Phlebotomy resulting in controlled hypovolemia to prevent blood 
loss in major hepatic resections 
 
Principal Investigator (PI):  Dr. Guillaume Martel, (613) 737-8899 x76979 
 
Sponsor: Ottawa Hospital Research Institute (OHRI) 
 
Funding: Canadian Surgical Research Fund 
  
Participation in this study is voluntary. Please read this Participant Informed Consent Form 
carefully before you decide if you would like to participate. Ask the study doctor and study team as 
many questions as you like. We encourage you to discuss your options with family, friends and/or 
your healthcare team.   
 
Why am I being given this form?  
 
You are being asked to participate in this research study because you are a patient who will be 
having a portion of the liver removed surgically (liver resection), here at The Ottawa Hospital. We 
want to help reduce bleeding during and after this operation. The information we learn from this 
study will also help us plan a bigger national study in the future. 
 
 
Why is this study being done? 
 
Major liver surgery, the procedure that you will be having, can sometimes lead to significant blood 
loss or hemorrhage. Blood loss in liver surgery is a key reason for worse outcomes and 
complications after surgery. Sometimes, blood loss may require you to have a blood transfusion. 
Research studies in North American hospitals suggest that up to one quarter of patients require a 
blood transfusion at the time of surgery or shortly after. Blood transfusions are usually very safe, 
but they can lead to allergic reactions or to the transmission of infectious diseases in extremely 
rare cases. 
 
Surgeons and anesthesiologists utilize many techniques to decrease the risk of bleeding and 
hemorrhage during liver surgery. Many of these techniques will be used during your surgery, as 
they are part of the standard of care. 
 
The goal of this research is to determine if whole blood phlebotomy will reduce bleeding and blood 
transfusion in patients having a liver operation.  
 
Phlebotomy is a simple technique for which the anesthesiologist removes one or two pints of blood 
from you into a special collection bag. This is done in a similar fashion as if you were donating 

 
 
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blood at a blood donation clinic. The exact amount of blood is decided upon based on your body 
weight (7-10 mL/kg). This will be done while you are asleep and the surgery is underway. You will 
be carefully monitored by the anesthesiologist. Your blood will never leave the sterile collection 
bag, specifically designed for that purpose. Once the liver surgery is completed, but before you 
wake up, your blood will be given back to you.  
 
This technique is thought to decrease the pressure within the large veins of the liver (known as the 
hepatic veins). As a result, we expect less bleeding while the liver is being cut. As mentioned, 
once the piece of liver is removed from you, your blood will be given back to you. 
 
We estimate that 62 participants will be enrolled in the study from The Ottawa Hospital. 
 
How is the study designed? 
 
Whether you get the surgery by the usual method or the usual method plus phlebotomy will be 
decided randomly.  Randomization means that you are put into a group by chance, similar to 
flipping a coin.  
 
This study will be double-blinded, which means that you will not be told in advance if you will have 
the phlebotomy during surgery or not. Your surgeon will also not know what you are receiving; 
only the anesthesiologist will be aware of the intervention and only after surgery is underway. 
Blinding helps to remove any bias or pre-conceived notions from affecting the outcome of the 
study. You will be told 30 days after surgery. 
 
What is expected of me? 
If you decide to participate in this study, you will undergo a major liver resection, as explained by 
your surgeon. There is nothing required of you as part of this study. 
Your stay in hospital and the care you receive will not be affected by this study. After you are 
discharged from hospital, you will have appointments scheduled to visit your surgeon on a regular 
basis. This will happen whether you participate in the study or not. If you choose to participate, all 
data will be collected while you remain admitted in hospital, as well as at the postoperative clinic 
visits. You will not have anything extra to do. You may be called once by the study coordinator one 
month after surgery. 
How long will I be involved in the study? 
 
Phlebotomy is a short-term intervention. It will only last for the duration of your liver surgery, while 
you are asleep under anesthesia. All relevant data to be collected after surgery will be available 
within 30 days of the operation. Your participation in the study will last during the time of surgery 
and the one telephone call one month after surgery.  
 
Your participation in the study may be stopped for any of the following reasons: 
• 
The study doctor feels it is in your best interest.  
• 
You need treatment that would interfere with the study. 
• 
You do not follow the study staff’s instructions. 
 
What are the potential risks I may experience?  
 
It is unlikely that phlebotomy will result in more risk than the standard of care. Previous research 
using this technique has not shown any special additional risk associated with receiving a 

 
 
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phlebotomy. In fact, previous research suggests that patients receiving phlebotomy bleed less 
during surgery and have the same risk of complications as other liver surgery patients. 
Phlebotomy could theoretically lead to any physiologic effect associated with blood loss. These 
effects could have implications for any major organ system, due to decreased blood flow. These 
could include but are not limited to myocardial ischemia (heart attack), cerebrovascular accident 
(stroke), acute renal failure (kidney failure) possibly requiring dialysis, coagulopathy (blood clotting 
abnormalities), or hepatic insufficiency (liver failure). That being said, these risks already exist with 
any liver surgery, simply on the basis of potentially significant blood loss. In order to be considered 
for liver surgery, you have already been seen by your surgeon and considered fit enough. Patients 
who are fit enough for liver surgery can also generally tolerate phlebotomy. You were asked to 
participate in the study because you met special study criteria based on your medical history, and 
this makes you eligible to participate in our study. 
 
In addition, there is always a small chance of risks that we do not know about. The potential 
extremely rare additional risks we know about are listed below: 
 
 Potential risk for clerical error with the blood (<1%) 
 Theoretical risk of bacterial contamination of the collection bag, tubing, and as a 
consequence, whole blood (<1%) 
 
Risks of Insurability: 
 
We will take all reasonable steps to keep your research information confidential. Should someone 
not involved in the research find out that you took part in this research study, or if you choose to 
share your results (if they are provided to you), there is a possibility that this could affect your 
insurability under certain policies of insurance, depending on the exclusions in such policies. 
Can I expect to benefit from participating in this research study? 
 
You may not receive any direct benefit from your participation in this study.  Your participation may 
allow the researchers to provide better treatments in the future for participants who need the same 
operation.  
 
This study will select by chance which treatment you will receive.  Participants in one arm of this 
study may do better or worse than participants in the other arm.   
 
Do I have to participate? What alternatives do I have? 
 
You can choose not to participate in this study. If you choose not to participate, you will still 
receive the usual operation that is done for your liver resection. Your study doctor will discuss this 
option with you. 
 
Your participation in this study is voluntary.  You may decide not to be in this study, or to be in the 
study now, and then change your mind later without affecting the medical care, education, or other 
services to which you are entitled or are presently receiving at this institution.   
 
If I agree now, can I change my mind and withdraw later? 
 
You may withdraw from the study at any time without any impact on your current or future care at 
this institution.  
 If you decide to stop your study participation, you need to tell your surgeon or your nurse 
before you have your operation. 

 
 
15 October 2018   
 
 
 
 
 
 
 
 
 
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 You may also choose to discontinue your participation in the study.  
 If you withdraw your consent, the study team will no longer collect your personal health 
information for research purposes, unless it is needed for review of safety.  
 
What compensation will I receive if I am injured or become ill in this study? 
 
In the event of a study-related injury or illness, you will be provided with appropriate medical 
treatment and care.  Financial compensation for lost wages, disability or discomfort due to an 
injury or illness is not generally available.  You are not waiving any of your legal rights by agreeing 
to participate in this study.  The study doctor and The Ottawa Hospital Research Institute still have 
their legal and professional responsibilities.  
 
Will I be paid for my participation or will there be any additional costs to me?  
 
The phlebotomy procedure will be provided to you free of charge as long as you are participating 
in the study. However, you will not receive any payment or have to pay for anything if you 
participate in this study. 
 
How is my personal information being protected? 
 
 
If you decide to participate in this study, the investigator(s) and study staff will look at your 
personal health information and collect only the information they need for this study. 
“Personal health information” is health information about you that could identify you 
because it includes information such as your name, address, telephone number, date of 
birth, new and existing medical records, or the types, dates and results of various tests 
and procedures. 
 
Information that identifies you will be released only if it is required by law.  
 
All information collected during your participation in this study will be identified with a 
unique study number (for example participant # AB01), and will not contain information 
that identifies you.   
 
Documents or samples leaving the Ottawa Hospital will only contain the coded study 
number.  
 
A Master List provides the link between your identifying information and the coded study 
number. This list will only be available to Dr. G. Martel and his staff and will not leave this 
site. 
 
The Master List and coded study records will be stored securely.  
 
You will not be identified in any publications or presentations resulting from this study. 
 For audit purposes only, your original study records may be reviewed under the supervision 
of  Guillaume Martel’s staff by representatives from: 
o the Ottawa Health Science Network Research Ethics Board (OHSN-REB),  
o The Ottawa Hospital Research Institute. 
 Research records will be kept for 10 years, after this time they will be destroyed.  
 Research records will be kept for 10 years, as required by the OHSN-REB.  
 
A description of this clinical trial is available on http://www.ClinicalTrials.gov (NCT02548910). This 
Web site will not include information that can identify you.  At most, the Web site will include a 
summary of the results. You can search this Web site at any time. 
 
 
Do the investigators have any conflicts of interest? 
 
There are no conflicts of interest to declare related to this study. 
 

 
 
15 October 2018   
 
 
 
 
 
 
 
 
 
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Page 43 of 51 
 
What are my responsibilities as a study participant? 
 
It is important to remember the following things during this study:  
• 
Ask your study doctor or the study coordinator if you have any questions or concerns. 
• Call the study doctor if you experience any side effects, even if you are unsure whether it 
has anything to do with this study.    
 
 
Will I be informed about any new information that might affect my decision to continue 
participating? 
 
You will be told in a timely fashion of any new findings during the study that could affect your 
willingness to continue in the study.  You may be asked to sign a new consent form. 
Who do I contact if I have any further questions?  
 
If you have any questions about this study, or if you feel that you have experienced a study-related 
injury or illness, please contact Dr. Guillaume Martel at 613-737-8899 x76979 or the study staff at 
613-737-8899 x 71484. 
 
The Ottawa Health Science Network Research Ethics Board (OHSN-REB) has reviewed this 
protocol.  The Board considers the ethical aspects of all research studies involving human 
participants at the Ottawa Hospital Research Institute. If you have any questions about your rights 
as a study participant, you may contact the Chairperson at 613-798-5555, extension 16719.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
15 October 2018   
 
 
 
 
 
 
 
 
 
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Page 44 of 51 
 
 
                 
                  
                                    
 
Consent to Participate in Research 
 I understand that I am being asked to participate in a research study on reduction in blood loss 
during major liver resection via the phlebotomy procedure. 
 This study was explained to me by ___________________________.  
 I have read, or have had it read to me, each page of this Participant Informed Consent Form.   
 All of my questions have been answered to my satisfaction.   
 If I decide later that I would like to withdraw my participation and/or consent from the study, I 
can do so at any time. 
 I voluntarily agree to participate in this study. 
 I will be given a copy of this signed Participant Informed Consent Form. 
 
________________________ 
 _________________________   _______________ 
Participant’s Printed Name  
  Participant’s Signature 
 
   Date 
 
Investigator or Delegate Statement  
I have carefully explained the study to the study participant.  To the best of my knowledge, the 
participant understands the nature, demands, risks and benefits involved in taking part in this 
study.   
 
_________________________ 
__________________________        _____________ 
Investigator/Delegate’s Printed     Investigator/Delegate’s Signature       Date 
 
Assistance Declaration  
Was the participant assisted during the consent process?   Yes 
 No 
 
  The consent form was read to the participant/substitute decision-maker, and the person signing 
below attests that the study was accurately explained to, and apparently understood by, and 
consent was freely given by the participant/substitute decision-maker.  
  The person signing below acted as a translator for the participant/substitute decision-maker 
during the consent process.  He/she attests that they have accurately translated the information 
for the participant/substitute decision-maker, and believe that the participant/substitute decision-
maker has understood the information translated. 
 
___________________________     _________________________       ____________  
Name of Person Assisting (Print)       Signature   
 
                     Date 
 
 
 
 
French 

 
 
15 October 2018   
 
 
 
 
 
 
 
 
 
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Page 45 of 51 
     
                           
                              
 
 
FORMULAIRE DE CONSENTEMENT ÉCLAIRÉ À L’INTENTION DU PARTICIPANT 
 
Titre de l’étude : L’essai clinique PRICE : phlébotomie et hypovolémie contrôlée visant à prévenir 
les pertes sanguines lors de résections hépatiques majeures 
 
Chercheur principal : Dr. Guillaume Martel, 613-737-8899 x71053 
  
Sponsor: Institut de recherche de l’Hôpital d’Ottawa (IRHO) 
 
Appui financier: Canadian Surgical Research Fund 
 
Votre participation à cette étude s’effectue sur une base entièrement volontaire. Veuillez lire ce 
formulaire de consentement soigneusement avant de décider si vous souhaitez participer. Posez 
au médecin responsable de l’étude et à l’équipe responsable de l’étude autant de questions que 
vous le souhaitez. Nous vous encourageons à discuter de vos options avec votre famille, vos amis 
ou votre équipe soignante. 
 
 
Pourquoi me remet-on ce formulaire ?  
 
On vous invite à prendre part à cette étude de recherche parce que vous allez avoir une opération 
visant à réséquer une portion de votre foie (résection hépatique), afin de traiter une tumeur dans 
cette partie du corps et ce, à l’Hôpital d’Ottawa. Cette étude vise à réduire le saignement encouru 
pendant et après cette chirurgie. L’information acquise durant cette étude servira aussi à la 
planification d’une autre plus grande étude, à l’échelle nationale. 
 
Pourquoi effectue-t-on cette étude ? 
 
La chirurgie hépatique majeure, la procédure que vous allez avoir, peut parfois occasionner des 
pertes sanguines importantes ou une hémorragie. Le saignement durant la chirurgie du foie peut 
entraîner des résultats défavorables ou complications suite à la chirurgie. Les pertes sanguines 
peuvent aussi entraîner une transfusion sanguine. Plusieurs études nord-américaines ont 
démontré que jusqu’à un quart des patients requirent une transfusion sanguine pendant ou après 
la chirurgie. Malgré que les transfusions sanguines soient d’habitude très sécuritaires, elles 
peuvent très rarement amener des réactions allergiques ou la transmission de maladies 
infectieuses. 
 
Les chirurgiens et anesthésistes se servent de techniques variées afin de minimiser le risque de 
saignement ou de transfusion durant toute chirurgie hépatique. Plusieurs de ces techniques seront 
utilisées durant votre opération, puisqu’elles font partie du standard de pratique. 
 
Cette étude a pour but de déterminer si la phlébotomie de sang complet peut amener une 
réduction du saignement ou du taux de transfusion chez les patients subissant une chirurgie du 
foie. 
 
La phlébotomie est une technique simple pour laquelle l’anesthésiste vous retirera un ou deux 
pintes de sang et ce dans un sac de collection spécialement conçu. La procédure est semblable à 
tout don de sang, qui pourrait avoir lieu dans une collecte de dons. La quantité exacte de sang à 
prélever est déterminée par votre poids (7-10 mL/kg). Le prélèvement aura lieu lorsque vous serez 
endormi sous anesthésie, durant la chirurgie. L’anesthésiste vous surveillera étroitement durant 

 
 
15 October 2018   
 
 
 
 
 
 
 
 
 
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toute la procédure. Votre sang ne quittera jamais le sac de collection stérile, conçu à cet effet. 
Suite à votre chirurgie du foie, votre propre sang vous sera redonné et ce avant que vous vous 
réveilliez.  
 
Il est postulé que cette technique sert à diminuer la pression dans les grandes veines du foie (les 
veines sus-hépatiques). Par conséquent, nous nous attendons à encourir moins de saignement 
pendant la coupe du foie. Tel qu’indiqué, votre sang vous sera redonné une fois que nous avons 
terminé d’enlever le morceau de foie. 
 
Nous anticipons la participation d’environ 62 patients à l’Hôpital d’Ottawa. 
 
Quelle est la méthodologie de l’étude ? 
 
L’affectation à la chirurgie avec phlébotomie plus méthode usuelle ou à la méthode usuelle 
s’effectuera aléatoirement. Cela signifie que vous serez affecté à un groupe au hasard, comme 
tirer à pile ou face. 
 
Cette étude s’effectuera à double-insu, ce qui signifie que vous ne serez pas informé du groupe 
auquel vous aurez été affecté (phlébotomie ou méthode usuelle). Votre chirurgien ne saura pas à 
quel groupe vous aurez été affecté; seul votre anesthésiste sera au courant de l’intervention et ce 
uniquement lorsque votre chirurgie sera en cours. Les études à l’insu permettent d’éliminer tout 
biais ou toute notion préconçue qui pourraient influer sur les résultats de l’étude. Vous serez 
informé du groupe auquel vous avez été affecté 30 jours après la chirurgie.  
 
Que serai-je appelé à faire ? 
 
Si vous décidez de participer à cette étude, vous allez subir une résection hépatique majeure, telle 
qu’expliquée par votre chirurgien. Vous n’aurez rien à faire de spécial durant cette étude. 
 
Votre séjour à l'hôpital et les soins que vous recevrez ne seront pas affectés par votre participation 
à cette étude. Suite à votre sortie de l'hôpital, vous aurez des rendez-vous de contrôle avec votre 
chirurgien, sur une base régulière. Ce sera le cas, que vous participez à l'étude ou non. Si vous 
choisissez de participer à l’étude, toutes les données nécessaires seront amassées à partir de 
votre dossier médical durant votre hospitalisation, ainsi que durant vos rendez-vous en clinique 
suite à votre congé. Vous n’aurez rien de spécial à faire. Il est possible que la coordinatrice de 
l’étude vous appelle une fois, un mois après la chirurgie. 
 
 
Quelle sera la durée de ma participation à cette étude ? 
 
La phlébotomie est une technique utilisée à court terme. Cette dernière se limite au temps de 
votre chirurgie, pendant que vous êtes sous anesthésie. Toutes les données nécessaires à l’étude 
seront disponibles durant les premiers 30 jours suivant votre chirurgie. Pendant cette période, 
vous n’aurez rien à faire. Votre participation à l’étude durera le temps de votre chirurgie, ainsi que 
pour un appel téléphonique environ 30 jours après votre chirurgie. 
 
On pourrait mettre fin à votre participation à cette étude, pour l’une ou l’autre des raisons 
suivantes : 
• 
Le médecin de l’étude croit que cela est dans votre intérêt fondamental.  
• 
Vous avez besoin de traitements additionnels qui pourraient interférer avec l’étude. 
• 
Vous ne respectez pas les consignes du personnel de l’étude. 
 
Quels sont les risques possibles associés à ma participation à cette étude ?  
 

 
 
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Il est peu probable que l’utilisation de la phlébotomie se traduise en une augmentation du taux de 
complications, par rapport à la technique usuelle. Les études de recherche antérieures portant sur 
la phlébotomie n’ont pas démontré de risques particuliers additionnels reliés à l’utilisation de cette 
technique. En fait, ces études semblent démontrer que les patients recevant une phlébotomie 
subissent moins de pertes sanguines et ce avec le même taux de complications que les autres 
patients ayant une chirurgie du foie. 
La phlébotomie peut théoriquement occasionner toute réaction physiologique reliée à la perte de 
sang. Ces réactions pourraient avoir des effets pour tous les systèmes d’organes majeurs et ce 
suite à une réduction du flux sanguin régional. Ces effets pourraient inclure (mais ne sont pas 
limités à ces derniers) un infarctus du myocarde (crise cardiaque), un accident cérébrovasculaire 
(ACV), une défaillance rénale aiguë (défaillance des reins) qui pourrait nécessiter de la dialyse, 
une coagulopathie (anomalie reliée aux facteurs de coagulation), ou une insuffisance hépatique 
(défaillance du foie). Ceci étant dit, tous ces risques existent déjà avec toute chirurgie hépatique 
en vertu du potentiel de pertes sanguines importantes. De plus, tout patient étant considéré pour 
une chirurgie hépatique doit au préalable avoir été vu et déclaré assez en santé par le chirurgien. 
Les patients qui sont généralement assez en santé pour subir une chirurgie hépatique sont aussi 
généralement capables de tolérer une phlébotomie. On vous invite à participer à cette étude parce 
que vous remplissez certains critères de sélection basés sur votre historique médical; par 
conséquent on vous considère éligible à participer à cette étude. 
De plus, il existe toujours une petite possibilité de risques qui nous sont inconnus. Les risques 
potentiels qui sont extrêmement rares sont les suivants : 
 Risque potentiel d’erreur administrative avec le sang (<1 %) 
 Risque théorique de contamination bactérienne du sac de collection, de la tubulure et, par 
conséquent, du sang (<1 %) 
Risques relatifs à l’assurabilité :  
 
Nous prendrons toutes les mesures nécessaires pour maintenir la confidentialité de vos 
renseignements. Si une personne n’intervenant pas dans cette étude de recherche devait 
apprendre que vous avez pris part à cette étude, ou si vous deviez choisir de partager vos 
résultats (advenant que ces derniers vous soient remis), il est possible que cette information 
puisse influer sur votre assurabilité, selon la police d’assurance, et en fonction des exclusions 
relatives à de telles polices. 
 
Puis-je m’attendre à retirer des bienfaits en lien avec ma participation à cette étude? 
 
Il est possible que vous ne retiriez aucun avantage direct en prenant part à cette étude. Votre 
participation à cette recherche pourrait aider les chercheurs à améliorer les soins de patients 
ayant besoin de la même opération à l’avenir. 
 
L’affectation à la chirurgie avec phlébotomie s’effectuera aléatoirement. Les participants affectés à 
un groupe pourraient avoir de meilleurs ou pires résultats que ceux affectés à l’autre groupe 
 
Suis-je tenu de participer ? Quelles sont mes autres options ? 
 
Vous pouvez choisir de ne pas prendre part à cette étude. Si vous choisissez de ne pas y 
participer, vous serez opéré afin de réséquer votre tumeur, selon la technique usuelle en chirurgie 
hépatique. Votre médecin de l’étude discutera de ces options avec vous. 
 

 
 
15 October 2018   
 
 
 
 
 
 
 
 
 
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Votre participation à cette étude s’effectue sur une base entièrement volontaire. Vous pouvez 
choisir de ne pas prendre part à cette étude, ou d’y prendre part maintenant et changer d’idée plus 
tard, sans que votre décision n’influe sur vos soins médicaux, votre éducation ou tout service 
auquel vous avez droit ou dont vous bénéficiez actuellement dans cet établissement.   
 
Puis-je changer d’idée plus tard et mettre fin à ma participation ? 
 
Vous avez le droit de retirer votre consentement en tout temps, sans que votre décision n’influe 
sur la qualité de vos soins actuels ou éventuels dans cet établissement.  
 Si vous décidez d’interrompre votre participation à l’étude, vous devez le communiquer à 
votre chirurgien ou infirmière avant votre opération. 
 Vous pouvez également choisir de mettre fin à votre participation à l’étude. 
 Si vous retirez votre consentement, l’équipe de l’étude cessera de recueillir vos 
renseignements personnels sur la santé aux fins de la recherche, à moins que ces derniers 
soient requis à des fins de révision de la sécurité.  
 
À quel type d’indemnisation puis-je m’attendre si je devais subir un préjudice ou tomber 
malade en lien avec ma participation à cette étude ? 
 
Dans le cas peu probable d’effets secondaires ou de blessures, nous vous fournirons les 
traitements ou les soins médicaux nécessaires. La compensation financière pour la perte de 
revenu, l’invalidité ou tout malaise associé à une blessure n’est normalement pas offerte. En 
participant à cette étude, vous ne renoncez à aucun de vos droits légaux. Le médecin de l’étude et 
l’Institut de recherche de l’Hôpital d’Ottawa seront toujours tenus de respecter leurs 
responsabilités professionnelles et légales.  
 
Serai-je rémunéré pour ma participation à cette étude ou encourrai-je des frais additionnels 
en prenant part à cette étude ? 
 
La phlébotomie sera effectuée gratuitement, tant que vous participez à cette étude. Vous ne 
recevrez aucun paiement et n’aurez rien à débourser pour participer à cette étude.  
 
Comment assurera-t-on la protection de mes renseignements personnels ? 
 
 Si vous décidez de prendre part à cette étude, on vous assignera un code numérique qui 
sera utilisé pour toute la durée de l’étude et servira à identifier votre dossier, vos 
documents et résultats. 
 Une liste maîtresse servira de lien entre vos renseignements personnels et votre code 
numérique de l’étude. Seuls le docteur Martel ou son personnel pourront accéder à cette 
liste et cette dernière ne sera pas transmise à l’extérieur du site. 
 La liste maîtresse et les dossiers codés de l’étude seront entreposés de manière 
sécuritaire.  
 La divulgation de vos renseignements d’identification ne sera permise que si requise par la 
loi.  
 Tout document ou échantillon transmis à l’extérieur de l’Hôpital d’Ottawa sera codé à l’aide 
d’un code numérique de l’étude. Aucune publication ou présentation résultant de cette 
étude ne pourra servir à vous identifier. 
 Les représentants des établissements suivants pourront procéder à l’examen de vos 
dossiers médicaux originaux, sous la supervision du personnel du docteur Martel, 
uniquement à des fins de vérification : 
o Le Conseil d’éthique de la recherche du Réseau de science de la santé d’Ottawa 
(CÉR-RSSO) 
o l’Institut de recherche de l’Hôpital d’Ottawa. 

 
 
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 Les dossiers de recherche seront conservés pour une période de 10 années, 
conformément aux exigences de CÉR-RSSO 
 Une fois la période de rétention terminée, tous les dossiers papier seront déchiquetés ou 
jetés aux rebuts confidentiels, et les fichiers électroniques seront supprimés. 
 
Une description de cet essai clinique est disponible à l’adresse http://www.ClinicalTrials.gov 
(NCT02548910). Ce site Web ne renfermera aucun renseignement permettant de vous identifier. 
Tout au plus, le site Web présentera un résumé des résultats. Vous pouvez effectuer des 
recherches dans ce site Web en tout temps. 
 
Les chercheurs sont-ils aux prises avec des conflits d’intérêts ? 
 
Il n’existe aucun conflit d’intérêts à déclarer en lien avec cette étude.  
 
 
Quelles sont mes responsabilités à titre de participant à cette étude ? 
 
Il est important de se rappeler les choses suivantes au cours de cette étude : 
• 
Adressez-vous au chirurgien ou à la coordinatrice de l’étude si vous avez des questions ou 
des préoccupations. 
• 
Informez votre chirurgien de tout changement relatif à votre état de santé 
 
Serai-je informé de nouveaux renseignements qui seraient susceptibles d’influer sur ma 
décision de continuer à prendre part à cette étude ? 
 
Nous vous informerons dès que possible de tout nouveau renseignement qui serait susceptible 
d’influer sur votre volonté de continuer à prendre part à l’étude. Il est possible que vous soyez 
alors appelé à signer un nouveau formulaire de consentement. 
 
Avec qui communiquer si j’ai d’autres questions ?  
 
Pour toute question au sujet de l’étude, ou si vous croyez avoir été victime d’une blessure 
découlant de cette étude, veuillez communiquer avec le docteur Martel au (613) 737-8899 71053 
ou le personnel de l’étude au (613) 737-8899 x 71484.   
 
Le Conseil d’éthique de la recherche du Réseau de science de la santé d’Ottawa (CÉR-RSSO) a 
révisé ce protocole. Le CÉR-RSSO est chargé de l’ensemble des aspects éthiques de toutes les 
études de recherche menées auprès de sujets humains effectuées à l’Institut de recherche de 
l’Hôpital d’Ottawa. Pour toute question au sujet de vos droits à titre de sujet de recherche, veuillez 
communiquer avec le président du Conseil d’éthique de la recherche du Réseau de science de la 
santé d’Ottawa, au 613-798-5555, poste 16719.  
 
 
 

 
 
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Page 50 of 51 
                                   
                              
 
       
 
Consentement à la participation à la recherche 
 
 Je reconnais que l’on sollicite ma participation à une étude de recherche sur l’utilisation de la 
phlébotomie visant à minimiser les pertes sanguines en chirurgie hépatique 
. 
 _______________________________ m’a fourni les explications nécessaires au sujet de cette 
étude.  
 J’ai pris connaissance de chacune des pages de ce Formulaire de consentement éclairé à 
l’intention du participant.   
 On a répondu à toutes mes questions de manière satisfaisante.   
 Si je décide plus tard au cours de l’étude de retirer mon consentement, il me sera possible de le 
faire en tout temps. 
 Je consens volontairement à prendre part à cette étude. 
 On me remettra un exemplaire signé de ce Formulaire de consentement éclairé à l’intention du 
participant. 
 
 
___________________________________________________________________________ 
Nom du participant  
 
Signature du participant 
 
  
 
Date 
(en caractères d’imprimerie) 
 
 
 
 
Énoncé du chercheur ou du délégué  
 
J’ai expliqué soigneusement au participant à la recherche la nature de l’étude susmentionnée. 
Pour autant que je sache, le participant apposant sa signature à ce consentement reconnaît la 
nature, les exigences, les risques et les avantages que comporte sa participation à l’étude.  
 
 
__________________________________________________________________________ 
Nom du chercheur / délégué 
   
 
Signature 
 
  
  
Date 
(en caractères d’imprimerie) 
 
 
 
Déclaration relative à l’assistance  
 
Le participant a-t-il reçu de l’assistance au cours du processus de consentement ?  
  Oui  Non 
 
  On a lu le formulaire de consentement au participant / au mandataire et la personne apposant 
sa signature ci-dessous atteste avoir fourni des explications précises au participant / décideur 
substitut, qui semble l’avoir comprise et ce dernier a donné librement son consentement. 

 
 
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Page 51 of 51 
  La personne apposant sa signature ci-dessous a fait fonction de traducteur pour le participant / 
le décideur substitut au cours du processus de consentement. Elle atteste avoir traduit fidèlement 
l’information pour le participant / le décideur substitut, et je crois que le participant / le décideur 
substitut a compris l’information traduite. 
 
 
 
___________________________________________________________________________ 
Nom de la personne ayant fourni l’assistance   
Signature   
                   Date 
(en caractères d’imprimerie)