Evaluation of the Predictive Nature of the Postoperative CRP on Postoperative Recovery in Patients Undergoing Colorectal Resection
Phase: NA
Conditions: Colorectal Postoperative Complication
Sponsor: Centre Hospitalier Departemental Vendee

Version 5.0 of 13/04/2016 
1 
 
CRP-Track 
Coordinating Investigator : 
Doctor Emeric Abet 
PH digestive surgery CHD La-Roche-sur Yon 
emeric.abet@chd-vendee.fr 
 
 
 
 
 
 
CRP-track protocol 
 
 
Ref : CHD 065-14 
 
 
 
"Evaluation of the predictive character of postoperative CRP 
on postoperative recovery in patients operated for colorectal 
resection". 
 
 
 
 
Methodologist :  
Aurélie Le Thuaut 
Unité de Recherche Clinique, CHD Vendée 
02 44 76 68 47 
aurelie.le.thuaut@chu-nantes.fr  
 
 
Etablissement responsable de la recherche :  
 
 
 
 
 
Promoteur : 
CHD VENDEE Contact : Dr Jérôme Dimet 
Centre de Recherche Clinique,  
Bd S.Moreau – 85925 LA ROCHE SUR YON cedex 09 
Tel : 02 51 44 65 64 Fax : 02 51 44 62 98 
 

CRP-Track 
Version 5.0 of 13/04/2016 
2 
 
 
Title: Evaluation of the predictive character of postoperative CRP on postoperative recovery in 
patients operated for colorectal resection. "CRP-Track study 
IRCB registration number: 2014-A01597-40 
 
SIGNATURES 
 
INVESTIGATOR'S SIGNATURE 
I have read all the pages of the protocol for the clinical trial sponsored by CHD La 
Roche sur Yon. I confirm that it contains all the information required to conduct the 
trial. I undertake to carry out the trial in compliance with the protocol and the terms 
and conditions defined therein. I undertake to carry out the trial in compliance with : 
- 
the principles of the "Declaration of Helsinki", 
- 
the rules and recommendations of international (ICH-E6) and French (rules 
of good clinical practice for biomedical research involving medicinal 
products for human use - decisions of November 24, 2006) good clinical 
practice. 
- 
national legislation and regulations relating to clinical trials, 
- 
compliance with the EU Clinical Trials Directive [2001/20/EC], a copy of 
each of which has been provided to me by the sponsor. 
I also undertake that the investigators and other qualified members of my team will 
have access to copies of this protocol and the documents relating to the conduct of the 
trial to enable them to work in compliance with the provisions contained in these 
documents. 
 
NAME: Dr. Emeric ABET 
 
 
Signature: ..................................................... 
Date : 
 
 
 
SIGNATURES 
 
Sponsor : 
NAME: Yvon RICHIR, General Manager 
Signature: ...................................................... 
Date : 
Principal Investigator : 
CENTER : 
Date : 
NAME : 
Signature: ...................................................... 

CRP-Track 
Version 5.0 of 13/04/2016 
3 
 
 
SUMMARY 
 
 
Title of study 
"Evaluation of the predictive character of postoperative CRP 
dosage on postoperative recovery in patients operated for 
colorectal resection". 
Key words 
CRP / Postoperative complication / Length of stay 
Responsible for 
research 
CHD Vendée 
Coordinating investigator 
(if multicenter study) 
Doctor Emeric Abet 
Number 
of 
centers 
planned 
Bi-centric: La Roche sur Yon / Nantes 
Type of study 
Research evaluating routine care 
Study schedule 
❖ Total duration: 2 years and 3 months 
❖ Recruitment period: 2 years 
❖ Follow-up time per patient: 3 months post-operative 
Study design 
❖ Bi-centric 
❖ Uncontrolled 
❖ Prospective 
Study objectives 
Primary objective: 
To show that serum CRP <172mg/L on postoperative day 3this 
associated with postoperative recovery of less than 5 days 
(prognostic properties of serum CRP<172mg/L). 
Secondary objective(s): 
❖ Show a linear correlation between postoperative CRP value 
on day 3thand length of hospital stay after colorectal surgery 
❖ Show that postoperative 
CRP measurement 
prevents 
readmissions after patient discharge (<5%) 
❖ Show that postoperative CRP measurement enables early 
diagnosis of postoperative complications 
❖ Show  that  a  postoperative  CRP  assay  enables  early 
management of postoperative infectious complications 
❖ Evaluate the prognostic properties of other alternative 
markers in this indication (procalcitonin and Lactates) and 
those of these 3 markers on days 4thand 5th. Investigate 
whether a combination of the 3 markers provides better 
prognostic properties. 
Number of cases 
projected 
174 patients 
Schedule of visits and 
examinations 
This schedule corresponds to the usual visits and examinations. 

CRP-Track 
Version 5.0 of 13/04/2016 
4 
 
 
 
Main selection, 
inclusion, non-inclusion 
and exclusion criteria 
Main inclusion criteria : 
- 
Patient over 18 years of age 
- 
Programmed hospitalization for colonic resection with 
anastomosis without permanent or temporary digestive 
bypass 
- 
Patient with a preoperative CRP value less than or equal 
to 172 mg/L 
- 
Patient who has given his or her consent to participate in 
the study 
- 
Patient scheduled to return home after surgery (or 
convalescent home or non-medical institution) 
Main non-inclusion criteria : 
- 
Patient under guardianship, curatorship, 
- 
Person under protection or deprived of liberty 
- 
Minor patients 
- 
Patient treated as an emergency 
- 
Colectomy surgery with digestive bypass or other 
digestive anastomosis 
- 
Complex 
combined 
surgery 
(significant 
associated 
digestive resection, other surgical procedure that may 
interfere with postoperative CRP measurement) 
- 
General inflammatory diseases likely to affect assay 
values 
- 
Patients on long-term anti-inflammatory therapy (NSAIDs 
/ corticosteroids / immunosuppressants) 
- 
Patients unable to understand the proposed study 
Primary endpoint 
The 
de 
jugement 
de 
study 
composite criterion is: 
"Postoperative recovery related to the procedure" defined as 
follows: 
- 
Absence of pain >2 on the VAS scale 
- 
and presence of gaseous intestinal transit 
- 
And patient autonomy in terms of ambulation and 
personal care (GIR 5-6) 
- 
And absence of fever 
Secondary endpoint(s) 
- 
Patient length of stay (in days) 
- 
Patient readmission rate within 30 days of discharge 
- 
Number of sub-clinical anastomotic fistulas detected on 
imaging (abdomino-pelvic CT) if CRP 
> 172 mg/l 
- 
Number of re-interventions for postoperative anastomotic 
complications 
- 
Measurements of various biological parameters (serum 
procalcitonin / lactates / CRP) compared with length of 
hospital 
stay 
and 
occurrence 
of 
postoperative 
complications. 
Statistical analysis 
The prognostic properties of serum CRP on day 3e(at a threshold of 
172mg/L) for predicting postoperative recovery of less than 5 days 
will be measured (sensitivity, specificity, positive predictive value, 
negative predictive value). 
negative predictive value). The two groups (CRP<172 vs. 

CRP-Track 
Version 5.0 of 13/04/2016 
5 
 
 
 
CRP>172) will be compared on all variables. We will also assess the 
prognostic properties of serum CRP on days 4eand 5, measure 
those of serum procalcitonin and lactates (on days 3e, 4(e) and 5e) 
and look for a combination of these markers to improve the 
prognostic properties of postoperative recovery of less than 
than 5 days. 

CRP-Track 
Version 5.0 of 13/04/2016 
6 
 
 
LIST OF ABBREVIATIONS 
 
ARC 
Clinical Research Associate 
CNIL 
Commission Nationale de l'Informatique et des Libertés (French 
Data Protection Authority) 
Comité Consultatif sur le Traitement de l'Information en Matière de 
Recherche dans le Domaine de la Santé (Advisory Committee on 
the Processing of Health Research Information) 
CRF 
Case Report Form (observation booklet) 
IDE 
State Registered Nurse 
INSERM 
French National Institute for Health and Medical Research 
TEC 
Clinical Study Technician 
GNEDS 
Nantes Group for Health Ethics 
RNI 
Non-interventional research 
CCTIRS 

CRP-Track 
Version 5.0 of 13/04/2016 
7 
 
 
TABLE OF CONTENTS 
SUMMARY ............................................................................................................................................ 3 
LIST OF ABBREVIATIONS ............................................................................................................... 6 
LIST OF ABBREVIATIONS ............................................................................................................... 6 
TABLE OF CONTENTS ...................................................................................................................... 7 
INTRODUCTION ................................................................................................................................. 8 
1. 
RATIONALE FOR THE STUDY ................................................................................................ 9 
2. 
OBJECTIVES AND EVALUATION CRITERIA .................................................................... 12 
2.1. 
OBJECTIVE AND PRIMARY ENDPOINT ..................................................................................... 12 
2.2. 
SECONDARY OBJECTIVES AND EVALUATION CRITERIA .......................................................... 12 
3. 
STUDY POPULATION .............................................................................................................. 14 
3.1. 
DESCRIPTION OF THE POPULATION ........................................................................................ 14 
3.2. 
INCLUSION CRITERIA .............................................................................................................. 14 
3.3. 
NON-INCLUSION CRITERIA ..................................................................................................... 14 
4. 
STUDY PROCEDURE ................................................................................................................ 15 
4.1. 
GENERAL RESEARCH METHODOLOGY .................................................................................... 15 
4.2. 
RESEARCH AND ANALYSIS TECHNIQUES ................................................................................ 15 
4.3. 
STUDY SCHEDULE .................................................................................................................. 16 
4.4. 
CRITERIA FOR PREMATURE TERMINATION OF A PERSON'S PARTICIPATION IN RESEARCH18 
5. 
DATA MANAGEMENT AND STATISTICS ........................................................................... 19 
5.1. 
COLLECTION AND PROCESSING OF STUDY DATA .................................................................... 19 
5.2. 
STATISTICS ............................................................................................................................. 20 
6. 
SAFETY / UNDESIRABLE EFFECT ....................................................................................... 23 
7. 
JUSTIFICATION FOR REQUESTING VALIDATION OF RESEARCH IN ROUTINE 
CARE .................................................................................................................................................... 24 
8. 
ADMINISTRATIVE AND REGULATORY ASPECTS .......................................................... 25 
8.1. 
RIGHT OF ACCESS TO DATA AND SOURCE DOCUMENTS .......................................................... 25 
8.2. 
DATA CONFIDENTIALITY ........................................................................................................ 25 
8.3. 
COMPUTERIZED DATA AND SUBMISSION TO THE CNIL ......................................................... 25 
8.4. 
TRIAL MONITORING AND QUALITY CONTROL ........................................................................ 25 
8.5. 
PROTOCOL AMENDMENTS ...................................................................................................... 26 
8.6. 
ASSURANCE ........................................................................................................................... 26 
8.7. 
PUBLICATION RULES............................................................................................................... 26 
9. 
ETHICAL CONSIDERATIONS ................................................................................................ 27 
9.1. 
SUBMISSION TO AN ETHICS COMMITTEE ................................................................................ 27 
9.2. 
PATIENT INFORMATION .......................................................................................................... 27 
9.3. 
WRITTEN PATIENT CONSENT .................................................................................................. 27 
LIST OF APPENDICES ..................................................................................................................... 28 
APPENDIX 1: LIST OF INVESTIGATORS .............................. ERROR ! BOOKMARK NOT DEFINED. 
APPENDIX 2: BIBLIOGRAPHICAL REFERENCES .................................................................... 29 
APPENDIX 3: PATIENT INFORMATION NOTE ......................................................................... 30 
APPENDIX 4: OBSERVATION NOTEBOOK ................................................................................ 33 

CRP-Track 
Version 5.0 of 13/04/2016 
8 
 
 
INTRODUCTION 
The aim of this study was to evaluate the prognostic character of inflammatory marker 
assays (CRP, procalcitonin and venous lactates) on postoperative recovery after colorectal 
surgery. Over the past two decades, the management of patients undergoing colorectal 
resection has evolved considerably. Peri-operative management has been simplified, with no 
systematic drainage, no gastric tube, early resumption of feeding and rapid mobilization of 
patients. This modern approach to digestive surgery makes hospitalization simpler, reducing 
the length of time patients spend in hospital without increasing the risks, morbidity and peri- 
operative mortality. Most surgical teams have successfully implemented fast-track surgery. 
However, some patients will not be able to benefit from this approach because of 
postoperative events (infectious complications between 10 and 15%), prolonged ileus 
(between 10 and 20% of cases) or decompensation of an underlying co-morbidity. There are 
currently no predictive factors for early postoperative recovery. This study assesses the 
prognostic character of biological inflammatory parameters (CRP, Pro-calcitonin, lactates) on 
postoperative recovery, using assays at D3, D4 and D5. The stakes are twofold: to enable 
hospital beds to be planned in care facilities, and to improve individual patient management. 

CRP-Track 
Version 5.0 of 13/04/2016 
9 
 
 
1. RATIONALE FOR THE STUDY 
 
Colonic and rectal resections account for the majority of hospitalizations in visceral 
surgery departments. Colorectal cancer and diverticular disease are the main indications for 
colorectal surgery. The length of hospital stay after colorectal resection (for cancer or benign 
pathology) is conditioned by two main parameters: the patient's autonomy in terms of bowel 
movements and eating, and the physical ability to ambulate; and the need for in-hospital 
monitoring of the critical risk period for postoperative bleeding or infectious complications. It 
therefore depends on factors linked to the patient and the procedure itself. 
Among procedure-related parameters, postoperative pain, induced inflammatory 
reaction, postoperative ileus and the occurrence of infectious complications (surgical site 
infection, anastomotic fistula, deep abscess, postoperative peritonitis) are the parameters 
correlated with a longer hospital stay. 
In addition, most surgical teams involved in colorectal resections have recently set up 
early postoperative rehabilitation programs (Fast-track), with a view to optimizing 
postoperative recovery for patients, but also reducing the length of hospital stay. For selected 
patients, a 48-hour hospital stay is possible for a surgical colectomy. The patient is 
discharged from hospital before any bowel movements are resumed. One of the limitations of 
these programs is the absence of predictive parameters for complications, which would 
encourage prolonged inpatient monitoring. Similarly, there are no negative predictive factors 
that would enable patients to be discharged early and safely. At present, the average length 
of hospital stay for a patient undergoing colorectal resection is 10 days, with little variation 
between facilities. This compares with 15 days in the 1990s. Early rehabilitation programs 
published in the literature, without going as far as 48 hours in an authoritarian way, reduce 
this duration from 3 to 5 days, even before patients resume intestinal transit, with a 
postoperative readmission rate of around 20%. 
In this context, the definition of biological markers predictive of complications and 
prolonged hospital stay is a challenge for the future, with the aim of anticipating patients' 
postoperative recovery and the occurrence of complications. 
 
CRP is a serum protein synthesized exclusively by the liver and secreted in situations 
of systemic inflammation. It plays a role in innate immunity, activating serum complement 
and promoting phagocytosis in inflammatory foci. At 

CRP-Track 
Version 5.0 of 13/04/2016 
10 
 
 
 
Due to its short half-life, CRP represents an early non-specific marker of inflammation. In the 
context of abdominal surgery, and colorectal surgery in particular, CRP has been shown to 
correlate negatively with the occurrence of postoperative events (1). While elevated CRP is 
not predictive of complications, a low postoperative serum CRP level is correlated with the 
absence of complications such as anastomotic fistula (average frequency 10% after 
colorectal resection). Concerning the best time for this evaluation, whether the assay is 
performed on the 3rd, 4th or 5thpostoperative day, the negative predictive value is identical 
(80%), taking the value of 172 mg/L as the threshold. In addition to the occurrence of 
infectious complications, CRP has also been correlated with duration of surgery, 
intraoperative blood loss and severity of surgical trauma. To date, other biological markers of 
systemic inflammation or tissue distress, such as serum pro-calcitonin and venous lactates, 
have not been evaluated in this specific indication, but are of interest to teams looking for 
early markers of postoperative complications. 
The aim of our study is to assess the value of systematic serum CRP / Pro-calcitonin / 
Venous lactate measurement in the postoperative period as a predictor of recovery and 
length of hospital stay. This preliminary routine care study should enable patients' 
hospitalization and safe return home to be planned. 
 
The project's originality is twofold: from a scientific point of view on the one hand, and from a 
care organization point of view on the other. From a scientific point of view, CRP, which is 
already used in current clinical practice, has not been evaluated with a view to modulating 
the length of hospital stay. Yet this marker is linked to the main vectors of inflammation in 
digestive surgery (ileus and septic complications). Our work will therefore enable us to define 
an early marker of postoperative recovery that could modify the medical management of the 
post-operative period (removal of drains, earlier resumption of feeding). Our study will also 
enable us to compare different inflammatory markers that can be measured but are not 
routinely used in this indication. 
In terms of care organization, although outpatient surgery is playing an increasingly 
important role in the management of digestive surgery patients, there are still areas where 
conventional hospitalization is unavoidable. Nevertheless, the length of hospital stays has 
been considerably reduced over the last 10 years, without increasing perioperative morbidity. 
In order to generalize the effort to reduce hospitalization, we need simple, reproducible 
parameters that predict postoperative recovery time and complications. In addition, 
optimizing the management of care facilities (beds 
conventional hospitalization) 
requires   to forecast  and  to anticipate  the  duration 

CRP-Track 
Version 5.0 of 13/04/2016 
11 
 
 
 
for each patient undergoing scheduled surgery. In this context, the originality of our study lies 
in the evaluation of a low-cost marker already used routinely on an empirical basis in the 
post-operative follow-up of patients undergoing digestive surgery. 
 
Bibliographical references are given in the appendix. 

CRP-Track 
Version 5.0 of 13/04/2016 
12 
 
 
 
2. OBJECTIVES AND EVALUATION CRITERIA 
 
 
2.1. 
MAIN OBJECTIVE AND EVALUATION CRITERIA 
 
2.1.1. 
Main objective 
 
To show that a serum CRP <172mg/L on the 3rdpostoperative day is associated with a 
postoperative recovery of less than 5 days (evaluation of the prognostic properties of a 
serum CRP<172mg/L). 
 
2.1.2. 
Primary endpoint 
 
The primary endpoint of the study was a composite criterion: "Postoperative recovery related to the 
procedure". This criterion is defined as follows: 
- 
Absence of pain >2 on the VAS scale 
- 
Presence of gaseous intestinal transit 
- 
Patient autonomy in terms of ambulation and personal care (GIR 5-6) 
- 
Absence of fever 
 
 
2.2. 
SECONDARY OBJECTIVES AND EVALUATION CRITERIA 
 
2.2.1. 
Secondary objective(s) 
 
- 
Show a linear correlation between postoperative CRP value on day 3thand length 
of hospital stay after colorectal surgery. 
- 
Show that postoperative CRP measurement prevents readmissions after patient 
discharge (<5%) 
- 
Showing that a postoperative CRP assay enables early diagnosis of postoperative 
complications 
- 
Demonstrate that a postoperative CRP assay enables early management of 
postoperative infectious complications 
- 
Evaluate the prognostic properties of other alternative markers in this indication 
(pro-calcitonin and venous lactates) and those of these 3 markers on days 4thand 
5th. Investigate whether a combination of the 3 markers provides better prognostic 
properties. 
 
 
2.2.2. 
Secondary endpoint(s) 
 
- 
Patient length of stay (in days) 
- 
Patient readmission rate within 30 days of discharge 

CRP-Track 
Version 5.0 of 13/04/2016 
13 
 
 
 
- 
Number of sub-clinical anastomotic fistulas detected on imaging (abdomino-pelvic 
CT) if CRP > 172 mg/l 
- 
Number of re-interventions for postoperative anastomotic complications 
- 
Comparison of various biological parameters (serum pro-calcitonin / Lactates / 
CRP) with length of hospital stay and occurrence of postoperative complications. 

CRP-Track 
Version 5.0 of 13/04/2016 
14 
 
 
 
3. STUDY POPULATION 
 
 
3.1. 
DESCRIPTION OF THE POPULATION 
 
All adult patients seen in a surgical consultation and scheduled for colonic or rectal resection 
with restoration of unprotected digestive continuity could be included in the study. 
Given the activity of the 2 centers concerned, 174 patients out of an annual total of 230 will 
constitute the study population. 
 
 
3.2. 
INCLUSION CRITERIA 
 
Main inclusion criteria : 
- 
Patient over 18 years of age 
- 
Programmed hospitalization for colonic resection with anastomosis without 
permanent or temporary digestive bypass 
- 
Patient with preoperative CRP less than or equal to 172 mg/L 
- 
Patient having given his or her consent to participate in the study 
- 
Patient scheduled to return home after surgery (or convalescent home or non- 
medical institution) 
 
 
3.3. 
NON-INCLUSION CRITERIA 
 
Main criteria for non-inclusion : 
- 
Patient under guardianship, curatorship, 
- 
Person under protection or deprived of liberty 
- 
Minor patients 
- 
Patients under emergency care 
- 
Colectomy surgery with digestive bypass or other digestive anastomosis 
- 
Complex combined surgery (significant associated digestive resection, other 
operative procedure that may interfere with postoperative CRP determination) 
- 
General inflammatory diseases likely to affect assay values 
- 
Patients on long-term anti-inflammatory therapy (NSAIDs / corticosteroids / 
immunosuppressants) 
- 
Patients unable to understand the proposed study 

CRP-Track 
Version 5.0 of 13/04/2016 
15 
 
 
 
4. STUDY PROCEDURE 
 
 
4.1. 
GENERAL RESEARCH METHODOLOGY 
 
The research has the following characteristics: 
❖ Pathophysiological study 
❖ Bi-centric study, 
❖ Uncontrolled study, 
❖ Prospective study 
❖ Routine care study 
 
 
4.2. 
STUDY AND ANALYSIS TECHNIQUES 
 
4.2.1. 
Detailed description of evaluation parameters 
 
The primary endpoint is the CRP blood test. This assay is routinely performed at D3 and D5 
post-op in all medical analysis laboratories. It meets reference assay standards in individuals 
with no inflammatory syndrome (normal value < 5 mg/l). In the context of a surgical operation 
or during which an inflammatory syndrome is systematically present, the CRP value rises. 
Taking into account a threshold value of 172 mg/l corresponds to a value evaluated in the 
literature as predictive (if below this value) of the absence of anastomotic complication. We 
retained this value as a threshold predictive of overall postoperative recovery for patients. 
Our primary endpoint (postoperative recovery) is composite, to correspond as closely as 
possible to the definition of postoperative recovery (patient fit for discharge). To avoid the 
pitfall of patients waiting for a convalescent facility (patients alone at home), the sole criterion 
of "length of hospital stay in days" did not seem relevant to us for assessing this recovery. 
We therefore included in the definition all the parameters that group together post-operative 
recovery: pain, transit, absence of fever and patient autonomy. This defines a composite 
criterion, the main judgment criterion. 
 
 
4.2.2. 
Description of techniques and analyses 
 
Assays of the various biomarkers included in the study will be performed pre-operatively (for CRP) 
as well as on day 3(th)post-operatively and on days 4thand 5th. 
CRP, pro-calcitoninemia and blood lactates are performed according to the standards of the 
laboratories concerned for hospitalized patients. 
As part of standard practice, CRP is measured at D3 and D5 post-op, but not systematically at D4 
post-op. 
T o avoid any bias in the analysis of results, CRP assays should also be performed pre- 
operatively. 

CRP-Track 
Version 5.0 of 13/04/2016 
16 
 
 
 
Pro-calcitonin and venous lactate assays are not routinely performed in this specific 
indication. 
Samples will be transported according to the usual procedure applied in the respective 
departments. 
These assays require a blood sample to be taken outside standard practice on D4 (not 
routinely performed, unless there is the slightest clinical doubt). 
A total of 4 additional blood tubes will be required. 
Pre-operatively: CRP determination is performed on the same tube as the standard pre- 
operative ionogram - no additional tube is required. 
At D3: 1 additional tube for venous lactates, as CRP is performed routinely and pro- 
calcitonitis can be measured on the same tube as CRP. 
At D4: 2 additional tubes: 1 tube for venous lactates, 1 tube for CRP and pro-calcitonin 
At D5: 1 additional tube for venous lactates, as CRP is performed routinely and pro- 
calcitonin can be measured on the same tube as CRP. 
 
 
 
4.3. 
STUDY SCHEDULE 
 
Patients seen in the pre-operative consultation will be informed of the study. The information 
letter will be handed out during this consultation. Inclusion in the study will take place before 
the operation (the day before or the day of the operation) by confirming that the patient has 
no objection to taking part in the study. 
A CRP assay will be performed preoperatively after the patient has indicated that he/she does not 
wish to participate. 
Following the operation, the postoperative CRP assay will be carried out at the same time as 
the other assays (pro-calcitonin and lactates) on day 3th, then on days 4thand 
5thpostoperatively. In the interim, clinical follow-up of patients was in line with routine 
management. All postoperative events are recorded in the patient's clinical record. 
In the event of a postoperative complication occurring during hospitalization, the assessment 
and management will be in line with normal patient follow-up, and will be recorded in the 
patient's record book. These elements will be taken into account in the primary endpoint. 
Clinical data, biological and imaging tests, and diagnosis will be reported. If a re-intervention 
is necessary, the report will be attached, as will any medical treatment related to the 
complication. 
In the absence of any particular event, the patient's hospitalization will continue under the 
same conditions as usual. Every day during hospitalization, the various parameters used in 
the study analysis will be recorded in the patient's notebook. Biological assay values will also 
be recorded (samples taken on days 3, 4 and 5). The discharge date will be decided by the 
surgeon in charge of the patient, independently of the study, but will be recorded in the 
patient file and the research CRF. 
After discharge, the patient will be seen again in a postoperative consultation at 1 month, then at 
3 months for the end-of-study visit (usual follow-up). At each visit, a clinical examination will 
be performed. 

Version 5.0 of 13/04/2016 
17 
 
 
STUDY SCHEDULE 
CRP-Track 
 
 
 
Actions 
J-30 
(Pre-inclusion 
visit) 
J0 
(Inclusion 
visit) 
Every 
day 
During 
hospitalization 
D3 / D4 / D5 Date 
of 
discharge 
M1 
M3 
Study discharge 
Patient information 
X 
History 
X 
Clinical examination 
X 
X 
X 
X 
X 
X 
X 
Paraclinical examinations 
X 
X 
X 
X 
X 
X 
X 
Medical procedures (ECG...) Each 
procedure must be located on a line 
CRP 
measurement 
Pro-calcitoninemia 
Lactatemia 
X 
(CRP 
only) 
X 

CRP-Track 
Version 5.0 of 13/04/2016 
18 
 
 
 
 
4.4. 
CRITERIA 
FOR 
PREMATURE FROM 
THE 
OF A 
PERSON'S PARTICIPATION IN RESEARCH 
 
 
Please refer to the statistics section for details of the procedures and duration of follow-up for 
people who have prematurely stopped participating in the study. 
There are no criteria for premature termination of a person's participation in research, apart from 
the patient's death or withdrawal of consent. 

CRP-Track 
Version 5.0 of 13/04/2016 
19 
 
 
5. DATA MANAGEMENT AND STATISTICS 
 
 
5.1. 
STUDY DATA COLLECTION AND PROCESSING 
 
5.1.1. 
Data collection 
 
An observation notebook (CRF) will be created for each patient. All information required by the 
protocol must be provided in the CRF. It must include the data needed to confirm compliance 
with the protocol, and all the data required for statistical analysis, and to detect major deviations 
from the protocol. 
 
Data will be collected on a Clinsight database, developed by the Data Management team of the 
Nantes University Hospital Research Department. 
 
5.1.2. 
Data coding 
 
By signing this protocol, the principal investigator and all co-investigators undertake to keep 
confidential the identities of all patients participating in the study. 
The transmission of a person's data for research purposes will only be possible if a coding 
system is used; the presentation of research results must exclude any direct or indirect 
identification. 
 
A code will be set up for each patient. This code will be the only information to appear on the 
CRF, enabling the CRF to be traced back to the patient. 
The person in charge of the research will also code the patient data on any documents in his/her 
possession (reports of imaging or biological examinations, etc.) which are attached to the CRF. 
Only the first letter of the subject's surname and first name will be recorded, together with a 
coded number specific to the study, indicating the center number and the order of inclusion of 
subjects. 
Each investigating center will keep a correspondence file between the study code and the 
identity of subjects from its own center. None of this direct or indirect identification information 
will be available for study analysis, and will be kept only at the center concerned. 
Most assays are performed on the same tubes as routine assays. Samples will therefore be 
taken in the same way and at the same time as standard practice samples. Anonymized results 
will be entered with the other data on the study's general e-CRF. 

CRP-Track 
Version 5.0 of 13/04/2016 
20 
 
 
5.1.3. 
Data processing 
 
The collection of clinical data will be based on the creation of a clinical database and data entry 
masks similar to the observation book, in compliance with the protocol and regulations currently 
in force. 
The structure of the database and data entry screens will be approved by the research 
manager. 
 
 
5.2. 
STATISTICS 
 
Name and contact details of analysis manager: Aurélie 
Le Thuaut 
Clinical Research Unit CHD 
Vendée 
Bd Stéphane Moreau - Les Oudairies 
85925 La Roche sur Yon 
aurelie.le.thuaut@chu-nantes.fr 
 
 
5.2.1. 
Description of 
methods 
statistics 
planned, 
including timing of planned interim analyses 
 
 
Primary endpoint: definition of the prognostic properties of using serum CRP at a threshold of 
172mg/L on day 3thto predict postoperative recovery of less than 5 days: Sensitivity, Specificity, 
positive predictive value (PPV), negative predictive value (NPV). In particular, the NPV will be 
specifically studied, as it is this value that will associate a better postoperative recovery of less 
than 5 days with a serum CRP value on day 3e<172mg/L. 
A subgroup analysis according to the type of pathology (malignant or benign) will be carried out 
if the numbers in each group allow it. 
The sample will be split into two groups according to serum CRP value on day 3th(cut-off value 
172mg/L). Data will be analyzed and compared between these two groups using chi-square 
tests for categorical variables and Student's t tests for continuous variables, in particular for the 
variables "readmission after patient discharge", 
"postoperative complications" and "postoperative infectious complications". 
Linear correlations between serum CRP on day 3eand the following variables will be estimated: 
• 
Length of hospital stay 
• 
Serum CRP on days 4thand 5th 
• 
Procalcitonin on days 3th, 4 and 5(th) 
• 
Lactates on days 3(th) , 4thand 5(th) 
The prognostic properties of serum CRP, procalcitonin and lactate will be determined by looking 
for thresholds t h a t optimize the negative predictive value (the main prognostic criterion of 
interest). 

CRP-Track 
Version 5.0 of 13/04/2016 
21 
 
 
(the main prognostic criterion of interest), using cost minimization by assigning a cost of 3 for a 
false negative and a cost of 1 for a false positive. 
In order to avoid any bias in the analysis of results, CRP measurement will be performed pre- 
operatively for all patients. 
 
 
 
5.2.2. 
Statistical justification of the number of inclusions 
 
Determination of the number of subjects required is based on the desired precision of the 
Negative Predictive Value. Preliminary data are obtained from the article by Singh et al (BJS, 
2014). In this article, a meta-analysis is used to determine the prognostic values of serum CRP 
on anatomical leakage in colorectal surgery. 
 
Based on this article, 72% of patients had a serum CRP below 172 mg/L (patients on whom 
NPV can be estimated). In addition, the NPV was estimated at 97%. To obtain a precision (half- 
width of the 95% confidence interval) on the NPV of 3%, we would need 125 patients with a 
serum CRP below 172mg/L, i.e. 174 patients in total. 
 
 
5.2.3. 
Expected level of statistical significance 
 
The expected level of significance is 5%. 
 
5.2.4. 
Statistical criteria for discontinuation 
 
There are no statistical stopping criteria. 
 
5.2.5. 
Method 
from catch in 
account of 
missing, unused or invalid data 
 
For the 3-day serum CRP value, in the presence of missing data, no imputation will be 
performed and the patient will not be analyzed. 
For the variable "postoperative recovery of less than 5 days", in the event of missing data, a 
"worst case" imputation will be performed, leading to these patients being considered as not 
having had a postoperative recovery of less than 5 days. In the event of a high rate of missing 
data (>5%) on this variable, a sensitivity analysis will be carried out using different imputation 
methods (average, multiple imputation, etc.). 
No imputation will be performed for other data. 

CRP-Track 
Version 5.0 of 13/04/2016 
22 
 
 
5.2.6. 
Management 
of 
modifications 
made 
to 
 initial strategy analysis plan 
 
There will be no changes to the initial strategy analysis plan, but additional analyses may be 
carried out. 
 
5.2.7. 
Selection of subjects for analysis 
 
 
All patients included in the study will be analyzed. 

CRP-Track 
Version 5.0 of 13/04/2016 
23 
 
 
6. SAFETY / ADVERSE EVENTS 
 
The occurrence of an adverse effect related to the patient's care during the present protocol will 
give rise to a declaration to the appropriate vigilance system (pharmacovigilance, biovigilance, 
hemovigilance, materiovigilance, etc.). 

CRP-Track 
Version 5.0 of 13/04/2016 
24 
 
 
7. JUSTIFICATION FOR REQUESTING VALIDATION OF 
RESEARCH IN ROUTINE CARE 
 
Taking all these factors into account, the person in charge of the research qualifies it as 
research in routine care, since : 
✓ All procedures are carried out in the usual way (biological samples for assessment, 
clinical data, surgical intervention). 
The research does not involve innovative or obsolete techniques or strategies. 
Blood samples will be taken as described in the usual post-operative check-ups. 
Additional assays are : 
- 
CRP assays pre-operatively and on D4 
- 
venous lactate and pro-calcitonin determinations on D3, D4 and D5 post-op. 
These assays require a blood test to be performed outside standard practice on D4 (not routinely 
performed, unless there is the slightest clinical doubt). 
A total of 4 additional blood tubes will be required. 
Apart from these tests, all other aspects of patient management will be identical to standard 
practice. In particular, the discharge date will be decided by the surgeon in charge of the patient, 
independently of the study and the results of the assays, but will be recorded in the patient file 
and the research CRF. 
 
 
As a result, the particular conditions under which the research is carried out represent negligible 
constraints for the person undergoing the research. (Article R 1121-3 of the French Public 
Health Code (CSP), Decree no. 2006-477 of April 26, 2006) 
 
The person in charge of the research will therefore submit the study protocol to the Comité 
de Protection des Personnes Ouest V de Rennes for a favorable opinion and confirmation of the 
research's qualification, prior to any implementation of the research, in accordance with article L 
1121-1 of the French Public Health Code (CSP), as amended by laws no. 2004-806 of August 9, 
2004 and no. 2006-450 of April 18, 2006 relating to public health policy. 

CRP-Track 
Version 5.0 of 13/04/2016 
25 
 
 
8. ADMINISTRATIVE AND REGULATORY ASPECTS 
 
 
8.1. 
RIGHT OF ACCESS TO DATA AND SOURCE DOCUMENTS 
 
Each patient's medical data will be transmitted only to the organization to which the person in 
charge of the research is attached, or to any person duly authorized by the latter, under 
conditions guaranteeing confidentiality. 
If necessary, the organization reporting to the person in charge may request direct access to the 
medical file in order to verify research procedures and/or data, without breaching confidentiality 
and within the limits authorized by laws and regulations. 
 
 
 
8.2. 
CONFIDENTIALITY OF DATA 
 
Persons having direct access will take all necessary precautions to ensure the confidentiality of 
information relating to the persons concerned, in particular as regards their identity and the 
results obtained. 
These persons, in the same way as the investigators themselves, are bound by professional 
secrecy (under the conditions defined by articles 226-13 and 226-14 of the French penal code). 
During or at the end of the research, the data collected on the subjects and transmitted by the 
investigators will be rendered anonymous. 
Under no circumstances may the names or addresses of the persons concerned appear in clear 
text. 
Only the first two letters of the subject's name and the first letter of his/her first name will be 
recorded, along with a coded number specific to the study indicating the order of inclusion of 
subjects. 
 
 
 
 
8.3. 
COMPUTERIZED DATA AND SUBMISSION TO THE CNIL 
 
Data collected during the study will be stored in a computer file in compliance with the French 
Data Protection Act of January 6, 1978, amended in 2004. 
The protocol will be submitted for CCTIRS approval, and the computerized processing will be 
subject to CNIL authorization. 
 
 
8.4. 
TRIAL MONITORING AND QUALITY CONTROL 
 
A Clinical Research Associate (CRA) will visit each site to carry out quality control of the data 
reported in the case report forms. 

CRP-Track 
Version 5.0 of 13/04/2016 
26 
 
 
The monitoring plan will be defined in consultation between the research team and the institution 
in charge, according to the objectives of the study and the internal procedure of the research 
department. 
On-site monitoring visits will be organized by appointment with the investigator. CRAs must have 
access to : 
- data collection notebooks for included patients, or the computerized database in the case of 
electronic observation notebooks 
- patients' medical and nursing records 
 
 
8.5. 
PROTOCOL AMENDMENTS 
 
An updated version of the amended protocol must be dated. The 
information note should be amended if necessary. 
Any amendment to the study protocol must be notified to the Comité de Protection des 
Personnes, to ensure that the proposed modifications do not alter the guarantees provided to 
research subjects. 
 
 
 
8.6. 
INSURANCE 
 
Insofar as the research is qualified as routine care research by the CPP, which means that there 
is no additional risk associated with the study, the insurance will be that of the establishment 
responsible for the care (article L. 1142-2). 
 
 
 
8.7. 
PUBLICATION RULES 
 
The center which has included the most patients will occupy the first position in author rank (first 
author the project leader of the center concerned). Successive ranks will then be assigned 
according to the number of patients included. The last author will be the other project leader 
concerned. 
A copy of the publication will be given to the CH La Roche-sur-Yon, the study leader, and to the 
CHU de Nantes, the participating center, which will necessarily be cited. 

CRP-Track 
Version 5.0 of 13/04/2016 
27 
 
 
9. ETHICAL CONSIDERATIONS 
 
 
9.1. 
SUBMISSION TO AN ETHICS COMMITTEE 
 
The person in charge of the research undertakes to submit the study project to a Comité de 
Protection des Personnes (CPP) for an ethical opinion. 
 
 
 
9.2. 
PATIENT INFORMATION 
 
 
The investigator undertakes to provide the patient with clear and accurate information about the 
protocol (information note in appendix). He will give the patient a copy of the information note. 
This will specify the patient's right to refuse to take part in the research and to withdraw at any 
time. Patients will be able to ask any questions they may have and obtain all the information 
they need to fully understand the project. 
 
 
9.3. 
WRITTEN PATIENT CONSENT 
 
 
As part of the project, the patient receives an information note containing a signature block, and 
gives the doctor a signed copy. This copy is kept in the patient's medical file. The patient keeps 
a copy himself. 

CRP-Track 
Version 5.0 of 13/04/2016 
28 
 
 
LIST OF APPENDICES 
 
❖ Listing of investigators 
❖ Bibliographical references 
❖ Patient information note 
❖ Observation booklet 

CRP-Track 
Version 5.0 of 13/04/2016 
29 
 
 
APPENDIX 1: BIBLIOGRAPHICAL REFERENCES 
 
Singh PP, Zeng IS, Srinivasa S, Lemanu DP, Connolly AB, Hill AG. Systematic 
review and meta-analysis of use of serum C-reactive protein levels to predict 
anastomotic leak after colorectal surgery. Br J Surg. 2014 Mar;101(4):339-46. doi: 
10.1002/bjs.9354. Epub 2013 Dec 5. 
. 
Ramanathan ML, Mackay G, Platt J, Horgan PG, McMillan DC. Impact of day 2 C- 
reactive protein on day 3 and 4 thresholds associated with infective complications 
following 
curative 
surgery 
for 
colorectal 
cancer. 
World 
J 
Surg. 
2013 
Nov;37(11):2705- 
10. doi: 10.1007/s00268-013-2177-4 
Garcia-Granero A, Frasson M, Flor-Lorente B, Blanco F, Puga R, Carratalá A, 
Garcia-Granero E. Procalcitonin and C-reactive protein as early predictors of 
anastomotic leak in colorectal surgery: a prospective observational study Dis Colon 
Rectum. 2013 Apr;56(4):475-83 
 
 
Zhu P, Liang Z, Fu J, Chen W, Wang Z, Jiang H, Cui L. Procalcitonin in abdominal 
exudate to predict prolonged postoperative ileus following colorectal carcinoma 
surgery. Int J Biol Markers. 2013 Jun 28;28(2):187-91. doi: 10.5301/jbm.5000028. 
 
Krpata DM, Keller DS, Samia H, Lawrence J, Obokhare I, Marderstein E, Brady KM, 
Delaney CP. Evaluation of inflammatory markers as predictors of hospital stay and 
unplanned readmission after colorectal surgeryPol Przegl Chir. 2013 Apr 
1;85(4):198- 
203. doi: 10.2478/pjs-2013-0030. 
Warschkow R, Beutner U, Steffen T, Müller SA, Schmied BM, Güller U, Tarantino I 
Safe and early discharge after colorectal surgery due to C-reactive protein: a 
diagnostic meta-analysis of 1832 patients. Ann Surg. 2012 Aug;256(2):245-50. doi: 
10.1097/SLA.0b013e31825b60f0. 
Debarros M, Steele SR. Perioperative Protocols in Colorectal Surgery Clin Colon 
Rectal Surg. 2013 Sep;26(3):139-145. 
 
Kehlet H. Fast-track colorectal surgery Lancet. 2008 Mar 8;371(9615):791-3 

CRP-Track 
Version 4.0 of 13/04/2016 
30 
 
 
Information note for research participation 
"Evaluation of the predictive character of CRP on postoperative 
recovery in patients undergoing colorectal resection surgery". 
Short title: "CRP-track 
APPENDIX 2: PATIENT INFORMATION NOTE 
 
 
 
 
 
 
Dear Sir/Madam 
 
The Digestive Surgery Department of the Centre Hospitalier Départemental Vendée de La 
Roche-sur-Yon and the Digestive and Endocrine Surgery Department of the Centre Hospitalier 
et Universitaire de Nantes are collaborating on a study of the prognostic effect of blood levels of 
inflammatory markers (CRP, pro-calcitonin and venous lactates) o n postoperative recovery 
after colorectal surgery. 
You are about to undergo colorectal resection surgery, and a number of blood tests will be 
performed during postoperative monitoring. In addition to standard CRP measurements, we 
would like to measure other markers such as pro-calcitonin and venous lactates as part of the 
"CRP-Track" study. 
The aim of this study is to determine whether these markers, which are specific to inflammation, 
could help predict the possible occurrence of postoperative events (surgical site infection or 
delay in resumption of intestinal transit) and the length of hospital stay following your colorectal 
surgery. 
Why this research? 
Ultimately, the aims of this study are to anticipate the length of post-operative recovery after this 
type of operation, which we know is decreasing; and at the same time, to predict the occurrence 
of complications. 
How will this research be carried out? 
 
This test is carried out on the basis of medical data collected during your usual care. 
With your consent, an additional CRP assay will be performed as part of your standard pre- 
operative blood test. 
Investigating physician 
Name: ..................................................................................................................... 
Department/institution: ............................................................................................. 
Institution Responsible for the research 
CHD de la Roche sur Yon - Boulevard Stéphane Moreau, 85 925 La Roche sur Yon 
Contact: Unité de recherche clinique du CHD de la Roche sur Yon : Dr Jérôme DIMET 
02 51 44 65 64 / jerome.dimet@chd-vendee.fr 
This document is given to the patient, whose participation is recorded in the medical 
record. 
A copy is kept outside the medical file, along with the study documents. 

CRP-Track 
Version 4.0 of 13/04/2016 
31 
 
 
After your operation, blood samples will be taken as part of your standard post-operative follow- 
up. With your agreement, CRP, pro-calcitonin and venous lactate measurements will be taken at 
D3, D4 and D5 post-op. 
These assays mean that you will have to take an additional blood sample at D4 post-op, 
whereas in standard practice you would only have had one at D3 and D5. 
 
This also represents the equivalent of 4 additional blood tubes in total over the 3 days of post- 
operative follow-up. These extra tubes are needed to perform these assays in addition to your 
standard biological tests. 
Your samples will be destroyed in accordance with the hospital's usual practice. 
 
Your participation in the research will not affect your treatment, with the exception of the blood 
samples specifically collected. 
This research will take place at the Centre Hospitalier Départemental Vendée de la Roche sur 
Yon and the Centre Hospitalier Universitaire de Nantes. 
It is planned to include 174 patients scheduled for colorectal resection surgery over a two-year 
period. 
 
What are your rights? 
 
The doctor in charge of your care will suggest that you take part in this study, and you are free to 
accept or refuse without having to justify your decision. 
Your treatment will be the same whether or not you take part in this research. Your 
participation in this research will not generate any additional costs for you. 
This research poses no risk to your health. The results will not provide information relevant to 
your health in particular. They will contribute to the development of knowledge in the field of 
colorectal surgery, and will need to be confirmed by further clinical studies, to enable the 
development of new diagnostic methods, and new surgical or therapeutic treatments. 
At your request, your doctor can inform you of the overall results of this research. 
In order to be carried out successfully, this research requires the computerized processing of 
your personal data to enable the results to be analyzed. A computer file containing your data will 
therefore be created. For reasons of confidentiality and to respect your privacy, your data will be 
systematically coded. Only the healthcare professionals personally in charge of your follow-up 
will have access to your personal data. 
 
Your data may be transferred to organizations other than CHU de Nantes, in France or abroad. 
In this case, your identity will be coded and you will not be identified. 
 
In accordance with the law, you have the right to access, oppose and rectify any data stored on 
your computer, at any time, through your doctor. You also have the right to object to the 
transmission of data covered by professional secrecy that may be used and processed as part 
of this 

CRP-Track 
Version 4.0 of 13/04/2016 
32 
 
 
research. You can exercise your rights of access and rectification by contacting the doctor 
mentioned at the beginning of this document. 
This study has been approved by the Comité Consultatif sur le traitement de l'information en 
matière de recherche (CCTIRS) and authorized by the Commission Nationale Informatique et 
Libertés (CNIL). 
In accordance with the French Public Health Policy Act, this research obtained a favorable 
opinion from the Comité de Protection des Personnes Ouest V de Rennes on 05/02/2015. 
You are free to accept or refuse to participate in the research presented to you. If you accept, 
you are free to change your mind at any time without having to justify your decision, and your 
decision will not prejudice the quality of your care. If you refuse to take part in the research, only 
the data necessary for your care will be collected and will not be used in the research. 
 
The doctor who proposed the research and gave you all the necessary information verbally can 
answer any questions you may have. 
 
 
To be completed by the investigator 
Patient's surname/first name .................................................................... Date 
information given: ........../........./............. 
The patient has not expressed any objection to participation in the study. 
Name of investigator: .................................................................................... Signature of 
investigator : 

CRP-Track 
Version 5.0 of 13/04/2016 
33 
 
 
APPENDIX 3: OBSERVATION BOOKLET 
 
Parameters entered in the database : 
 
 
Pre-operative demographic and administrative data: 
- 
First two letters of surname / and first letter of first name / month and year of birth 
 
- 
Inclusion date 
 
- 
Date of operation 
 
- 
Indication (pathology) 
 
- 
Medical history (heart disease / inflammatory disease / renal failure / respiratory 
disease / diabetes) 
- 
Usual treatment 
 
Parameters entered the day before surgery : 
- 
Infectious manifestations in the previous 10 days 
 
Procedure parameters : 
- 
Type of surgery (title) 
 
- 
Type of continuity restoration (surgical set-up) 
 
- 
Infectious event (surgical contamination) 
 
- 
Duration of operation 
 
- 
Approach (laparo / Coelio) 
 
Postoperative parameters (during hospitalization) 
- 
Daily: Temperature / pulse / EVA (in the morning) 
 
- 
Date of first gas 
 
- 
Date of first bowel movement 
 
- 
Date of first rising 
 
- 
Date of first access to hallway for ambulation (with or without assistance) 

CRP-Track 
Version 5.0 of 13/04/2016 
34 
 
 
- 
Date of discharge 
 
- 
Discharge orientation (home or care facility) 
 
Post-operative event 
- 
Infectious event: Date of diagnosis 
 
o Complementary imaging tests (results attached) 
 
o Surgical intervention 
 
o Radiological drainage 
 
- 
Prolonged Ileus (gastric tube maintained for more than 7 days or gastric tube 
inserted for more than 7 days) 
- 
Other complication (co-morbidity) 
 
Biological measurements 
Preoperative CRP 
CRP / Pro-Cal / Lactates D3 D4 D5 
Routine laboratory tests postponed: 
Hemoglobinemia to D5 
Transfusion if necessary White 
blood cell count on D5 
Postoperative urea / creatinine levels 
Visit 1 to 1 month 
Clinical examination / Treatment 
Visit 2 to 3 months: End of 
study Clinical examination / 
Treatment 
Interim hospital readmission 
Occurrence of a SAE (event likely to induce an inflammatory reaction)