Optimisation de la Surveillance Ambulatoire Des Insuffisants CArdiaques Par Télécardiologie (OSICAT)
Phase: NA
Conditions: Chronic Heart Failure
Sponsor: CDM e-Health

  
ClinicalTrials.gov version prepared on 15 SEP 2021 
 
 
 
Optimization of the Ambulatory Monitoring for Patients 
With Heart Failure by Tele-cardiology (OSICAT) 
 
 
 
 
 
ClinicalTrials.gov ID: NCT02068118 
 
 
 
 
 
STUDY PROTOCOL 
Version n° 14.0 dated 27 JUL 2018 revised on 06 SEP 2018 
 
 
 

 
 
 
 
Page 1 of 65   
OSICAT protocol / version 14.0 July 27, 2018 revised September 06, 2018               CDM e-Health 
English translation dated September 8, 2021 
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This document is the property of Air Liquide Group                               
 
 
 
Optimization of the Ambulatory Monitoring for Patients With 
Heart Failure by Tele-cardiology 
OSICAT 
Version 14.0 July 27, 2018 revised September 06, 2018 
English translation dated September 8, 2021 
 
RCB ID no.: 2012-A01672-41 
Study sponsor: 
CDM e-Health 
21 rue Albert Calmette – Building B4 
78350 JOUY-EN-JOSAS 
SIRET     538 835 489 00013 – APE 9609Z 
RCS        Versailles B 538 835 489 
 
Juan-Fernando RAMIREZ 
Vice President Medical R&D 
Fax: + 33 (0)  1 39 07 61 99 
Mobile: + 33 (0) 6  35 51 11 25 
 
Coordinating investigator: 
Prof. Michel Galinier 
University Professor, Hospital Cardiology Practitioner 
Head of Department, Cardiology Department A 
Rangueil Teaching Hospital Center  
1 avenue Jean Poulhès 
TSA 500 32 - 31059 TOULOUSE CEDEX 09 
Tel.: 05 61 32 26 61 
 
 
This protocol has been designed and drafted based on version 1.0 of 3 Sept. 2008 of the DIRC Sud-Ouest et Outre-Mer 
[Interregional Clinical Research Delegation - South-West and Overseas.

 
 
 
 
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OSICAT protocol / version 14.0 July 27, 2018 revised September 06, 2018               CDM e-Health 
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PROTOCOL UPDATE HISTORY 
VERSION 
DATE 
REASON FOR UPDATE 
V1 
21/01/2013 
Initial version submitted to the CPP 
V1.1 
19/03/2013 
Amended version following deliberation of the CPP on 15/02/2013 
V2.0 
14/10/2013 
Amendment no. 1: addition of investigating centers 
V3.0 
18/02/2014 
Amendment no. 2: addition of investigating centers 
V4.0 
17/04/2014 
Amendment no. 3: Extension of the inclusion period with change in 
the duration of the study 
V5.0 
08/01/2015 
Amendment no. 4: addition of investigating centers 
V6.0 
06/03/2015 
Amendment no. 5: addition of investigating centers and extension 
of the inclusion period with change in the duration of the study 
V7.0 
01/09/2015 
Amendment no. 6: addition of an investigating center 
V8.0 
07/01/2016 
Amendment no. 7: increase in the number of patients to be 
included, addition of an investigating center, change of main 
investigator of a center 
V9.0 
18/03/2016 
Amendment no. 8: change of name of the sponsor and extension of 
the inclusion period with change in the duration of the study 
V10.0 
28/11/2016 
Amendment no. 9: extension of the monitoring period for patients 
wishing to follow the tel-ecardiology program until its marketing 
date 
V11.0 
29/05/2017 
Amendment no.10: Up to date list of the investigators 
During the extension period, the patients will be contacted directly 
by the investigating centers
V12.0 
07/07/2017 
Amendment no.11: Creation of a principal investigators list 
independent from the protocol and updating of that list 
NA 
NA 
Amendment no.12: Updating of the investigators list 
V13.0 
21/02/2018 
Amendment no.13: Modification of the exploratory objective of the 
study 
V14.0 
27/07/2018 
revised 
06/09/2018 
Amendement no.14 :  
- Change of the contact person for the Sponsor 
- Addition of the Data Protection Officer 
- Addition of a Methodologist / Statistician and member of the 
Scientific Council 
- Harmonization of the retention period of documents and 
research data 
- Withdrawal of certain protocol annexes (information notes and 
patient consent forms, procedure and declaration form for SAE
 

 
 
 
 
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OSICAT protocol / version 14.0 July 27, 2018 revised September 06, 2018               CDM e-Health 
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MAIN CORRESPONDENTS 
 
Coordinating investigator 
Prof. Michel Galinier 
University Professor, Hospital Cardiology 
Practitioner 
Head of Department, Cardiology Department A 
Rangueil Teaching Hospital Center  
1 avenue Jean Poulhès 
TSA 500 32 - 31059 TOULOUSE CEDEX 09 
Tel.: 05 61 32 26 61 
 
Sponsor 
CDM e-Health 
21 rue Albert Calmette – Building B4 
78350 JOUY-EN-JOSAS 
SIRET     538 835 489 00013 – APE 9609Z 
RCS        Versailles B 538 835 489 
Juan-Fernando RAMIREZ 
Vice President Medical R&D  
Fax: + 33 (0) 1 39 07 61 99 
Mobile: + 33 (0) 6 35 51 11 25  
 
Data Protection Officer 
Laurence Thomazeau  
AIR LIQUIDE  
Data Protection Officer  
75, Quai d’Orsay  
75007 Paris - France  
https://www.airliquide.com/fr/groupe/contactez-
nous-rgpd 
 
Referring physician: 
Prof. Atul Pathak 
Cardiology Service 
Clinique Pasteur 
45 Avenue de Lombez - BP 27617 
31 076 TOULOUSE Cedex 3 
Tél : 05 62 21 16 99 
 
Methodology/statistician: 
Dr. Ruidavets Jean-Bernard                     
Epidemiology and community health laboratory 
- Teaching Hospital Center                  
INSERM UMR - U1027 
Faculty of Medicine  
37, allées J. Guesde 
31069 Toulouse France Cedex 9 
Tel.: 33 5 61 14 59 49  
Fax: 33 5 62 26 42 40                   
 
Prof. Bongard Vanina 
Epidemiology Service, CHU de 
Toulouse 
Département of Epidemiology,Health 
Economics and Public Health, 
Université Toulouse 3 Paul Sabatier 
UMR 1027 Inserm, Université 
Toulouse 3  
Tel : 33 5 61 14 59 19 
Fax : 33 5 62 26 42 40 
 
Methodology/drafting 
Clinical research center 
Dr. Claire Thalamas 
Dr. Anne Pavy-le-Traon 
Ms. Amandine Saubion 
Toulouse Purpan Teaching Hospital 
Center 
Pierre Paul Riquet Hospital 
2nd floor – Hall D 
1 place du Dr Baylac 
T.S.A 40031 
31059 Toulouse Cedex 09 
 
Other specializations: 
Prof. Laurent Molinier 
Medical Information Department 
INSERM UMR 1027 
2, rue Viguerie –TSA 80035 
31059 Toulouse Cedex 9 
Tel.: 33 5 61 77 85 90 
 
Prof. Anne Mayère 
University of Toulouse - IUT A 
CERTOP, UMR 5044 CNRS, 
ECORSE team 
115 Route de Narbonne 
31000 Toulouse 
Tel.: 05 62 25 89 52

 
 
 
 
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OSICAT protocol / version 14.0 July 27, 2018 revised September 06, 2018               CDM e-Health
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CONTENTS 
CONTENTS 
4 
1. 
PROTOCOL/SUMMARY OF THE RESEARCH 
8 
2. 
OVERALL DESCRIPTION AND RATIONALE OF THE STUDY IN THE LIGHT OF CURRENT 
KNOWLEDGE 
11 
2.1. 
CURRENT STATE OF KNOWLEDGE 
11 
2.1.1. 
heart failure 
11 
2.1.2. 
Management of heart failure 
12 
2.1.2.1. Current management 
12 
2.1.2.2. New management strategies 
13 
2.2. 
HYPOTHESES OF THE RESEARCH AND ANTICIPATED RESULTS 
16 
2.3. 
BENEFIT / RISK RATIO 
18 
2.4. 
EXTENSION PERIOD 
18 
3. 
OBJECTIVES OF THE STUDY 
18 
3.1. 
PRIMARY OBJECTIVES 
18 
3.2. 
SECONDARY OBJECTIVES 
19 
3.3. 
ASSESSMENT CRITERIA 
20 
3.3.1. 
Primary assessment criterion 
20 
3.3.2. 
Secondary assessment criteria 
20 
4. 
EXPERIMENTAL DESIGN 
22 
4.1. 
OVERALL STUDY DESIGN 
22 
4.2. 
RANDOMIZATION 
22 
4.3. 
STUDY SCHEDULE 
23 
4.4. 
STUDY EXTENSION PERIOD 
26 
5. 
ELIGIBILITY CRITERIA 
27 
5.1. 
INCLUSION CRITERIA 
27 
5.2. 
EXCLUSION CRITERIA 
27 
5.3. 
RECRUITMENT METHODS 
28 
5.4. 
INCLUSION CRITERIA DURING THE EXTENSION PERIOD 
28 
6. 
MANAGEMENT OF THE TELEMONITORING EQUIPMENT 
29 
6.1. 
SUPPLY OF THE EQUIPMENT 
29 
6.2. 
PACKING OF THE EQUIPMENT 
29 
6.3. 
LABELING OF THE EQUIPMENT 
29 
6.4. 
DISPATCH AND MANAGEMENT OF THE EQUIPMENT 
29 
6.5. 
MANAGEMENT OF THE TELEMONITORING EQUIPMENT DURING THE EXTENSION 
PERIOD 
30 
7. 
CONCOMITANT TREATMENT(S) AND PROCEDURE(S) 
30 
7.1. 
AUTHORIZED CONCOMITANT TREATMENT(S)/PROCEDURE(S) 
30 
7.2. 
FORBIDDEN CONCOMITANT TREATMENT(S)/PROCEDURE(S) 
30 
8. 
DESCRIPTION OF THE MEDICO-ECONOMIC ASSESSMENT 
30 
8.1. 
EFFICACY ANALYSIS 
31 
8.2. 
UTILITY ANALYSIS 
31 
8.3. 
COST ANALYSIS 
31 

 
 
 
 
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8.3.1. 
Standpoint adopted 
31 
8.3.2. 
Cost categories 
31 
8.3.3. 
Recording of the costs 
32 
8.3.4. 
Valuation of the costs 
32 
8.4. 
COST-EFFICACY ANALYSIS 
33 
8.5. 
COST-UTILITY ANALYSIS 
33 
8.6. 
DATA UPDATE 
34 
8.7. 
SENSITIVITY ANALYSIS 
34 
9. 
DESCRIPTION OF ASSESSMENT OF SOCIETAL ACCEPTABILITY 
34 
10. 
RESEARCH SCHEDULE 
36 
10.1. 
RESEARCH CALENDAR 
36 
10.2. 
SUMMARY TABLE OF PATIENT MONITORING 
37 
10.3. 
INCLUSION VISIT 
37 
10.4. 
TELEPHONE VISITS 
41 
10.5. 
PREMATURE END OF STUDY VISIT 
42 
10.6. 
RULES FOR TERMINATING THE RESEARCH 
42 
10.7. 
CONSTRAINTS RELATED TO THE RESEARCH AND POSSIBLE COMPENSATION OF THE 
PATIENTS 
42 
11. 
MANAGEMENT OF ADVERSE EVENTS AND NEW FACTS 
43 
11.1. 
DEFINITIONS 
43 
11.2. 
DESCRIPTION OF THE EXPECTED SERIOUS ADVERSE EVENTS 
44 
11.3. 
APPROACH TO BE ADOPTED IN CASE OF AN ADVERSE EVENT OR A NEW FACT 
44 
11.4. 
DECLARATION AND RECORDING OF UNEXPECTED SAES AND NEW FACTS 
45 
12. 
STATISTICAL ASPECTS 
45 
12.1. 
SAMPLE SIZE CALCULATION 
45 
12.2. 
STATISTICAL METHODS USED 
46 
13. 
MONITORING OF THE RESEARCH 
48 
14. 
RIGHTS OF ACCESS TO THE SOURCE DATA AND DOCUMENTS 
48 
14.1. 
ACCESS TO THE DATA 
48 
14.2. 
SOURCE DATA 
49 
14.3. 
DATA CONFIDENTIALITY 
49 
15. 
QUALITY CONTROL AND ASSURANCE 
50 
15.1. 
INSTRUCTIONS FOR DATA COLLECTION 
50 
15.2. 
MONITORING OF THE RESEARCH 
50 
15.3. 
QUALITY CONTROL 
50 
15.4. 
DATA MANAGEMENT 
51 
15.5. 
AUDIT AND INSPECTION 
52 
16. 
ETHICAL AND REGULATORY CONSIDERATIONS 
52 
17. 
STORAGE OF THE DOCUMENTS AND DATA RELATING TO THE RESEARCH 
54 
18. 
RULES CONCERNING PUBLICATION 
55 
18.1. 
SCIENTIFIC COMMUNICATIONS 
55 
18.2. 
COMMUNICATION OF THE RESULTS TO THE PATIENTS 
55 
18.3. 
ASSIGNMENT OF DATA 
55 
19. 
INVESTIGATOR'S AGREEMENT (SIGNATURE PAGE) 
56 

 
 
 
 
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OSICAT protocol / version 14.0 July 27, 2018 revised September 06, 2018               CDM e-Health
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BIBLIOGRAPHICAL REFERENCES 
57 
APPENDICES 
64 
APPENDIX 1: CORDIVA FOLDER 
64 
APPENDIX 2: IDENTIFICATION OF THE ALERT LEVELS 
65 
 
 
 

 
 
 
 
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OSICAT protocol / version 14.0 July 27, 2018 revised September 06, 2018               CDM e-Health
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LIST OF ABBREVIATIONS 
 
LTD: Long-Term Disease 
ANSM: French National Agency for Medicines and Health Products Safety 
BNP: Basic natriuretic peptide 
COPD: Chronic Obstructive Pulmonary Disease 
CCMP: Common Classification of Medical Procedures 
CRC: Clinical Research Center 
CNIL: French National Commission for Data Processing and Freedom 
CPP: Committee for the Protection of Persons 
CRAM: Regional Health Insurance Fund 
TPE: Therapeutic Patient Education 
ECG: ElectroCardioGraphy 
eCRF: electronic Case Report Form 
SAE: Serious Adverse Event 
UPG: Uniform Patient Groups 
UHG: Uniform Hospitalization Groups 
GSM: Global System for Mobile 
SRN: State Registered Nurse 
MSA: Agricultural Mutual Benefit Society 
NABM: Nomenclature of Medical Biology Procedures 
NIR: List Enrolment Number 
NYHA: New York Heart Association  
PMSI: IT System Medicalization Program 
RGTS: General Scheme for Employed Workers 
RSI: Social Security Scheme for Self-employed Workers 
ASS: Aftersales Service 
RAAS: Renin-Angiotensin-Aldosterone System  
CST: Clinical Study Technician 
T2A: Price per Activity 
LMV: Light Medical Vehicles 
GRDP: General Regulation on Data Protection  

 
 
 
 
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OSICAT protocol / version 14.0 July 27, 2018 revised September 06, 2018               CDM e-Health
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1. PROTOCOL/SUMMARY OF THE RESEARCH 
 
STUDY SPONSOR: CDM e-Health 
TITLE: Optimization of the Ambulatory Monitoring for Patients With Heart Failure by Tele-
cardiology - OSICAT 
MAIN INVESTIGATOR: Prof. Michel Galinier, Head of Department of the Cardiology 
Department 
Rangueil Teaching Hospital Center, TOULOUSE  
OBJECTIVES OF THE STUDY:  
Primary objective: To assess the impact of a tele-cardiology program on morbidity-mortality in 
heart failure patients versus standard monitoring.  
 
Primary assessment criterion:  
The primary assessment criterion is a composite criterion combining the number of unplanned 
hospitalizations for any cause and death from any cause during the 18-month comparative period 
in both groups. 
 
Secondary objectives: To: 
1) assess the effect of management by tele-cardiology versus standard management on 
hospitalizations and deaths of cardiovascular origin.  
2) compare the kinetics of evolution in quality of life between day 0 and month 18 in the 2 
groups.  
3) assess the differential cost-efficacy and cost-utility ratios of both patient management 
strategies. 
4) assess societal acceptability of management by tele-cardiology among healthcare professionals 
and patients. 
5) collect data concerning the hospitalizations and deaths during the extension period of the tele-
cardiology program among the patients who wished to participate in the latter.  
 
Secondary assessment criteria:  
1) Comparison of the number of events (deaths and hospitalizations of cardiovascular origin) 
between the 2 groups after 18 months. 
2) Comparison of the means of the Short Form-36 (SF-36) quality of life scale scores in the 
2 groups, at inclusion and at 18 months.  
3) Measurement of the annual cost of treatment in both groups from the point of view of the hospital 
and the health insurance scheme. 
4) Measurement of the social acceptability of the tele-cardiology program for patients and 
healthcare professionals 
5) Annualized numbers of hospitalizations for any cause, and numbers of deaths from any cause 
occurring during the extension period for the patients who wished to participate in the latter. 
6) Annualized numbers of hospitalizations and numbers of deaths of cardiovascular origin 
occurring during the extension period for the patients who wished to participate in the latter. 

 
 
 
 
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NUMBER OF PATIENTS: 990 patients (495 patients per group) 
RESEARCH DESIGN 
National, multicentric study. 
The patients will be randomized to one of the following 2 groups:  
- Standard management 
- Tele-cardiology: personalized telephone support and supervision of their signs and 
symptoms at home via telemonitoring. 
STUDY EXTENSION PERIOD 
All the patients who were included in the comparative period will be contacted by the 
investigating center to propose them an appointment with the investigating physician. During this 
appointment, the investigating physician will present this extension phase with continuation of the 
monitoring with the tele-cardiology program.  
The patients who accept to participate in the extension period will sign an informed consent form 
for this period. 
 
INCLUSION CRITERIA:  
- Men or women of 18 years of age or older.  
- Heart failure patients having been hospitalized for cardiac decompensation during the past 
12 months. 
- Patients having a landline telephone or with access to the GPRS network at their homes. 
- Patients having given their free informed written consent to participate in the study. 
- Patients subscribing to a social insurance scheme. 
 
INCLUSION CRITERIA DURING THE EXTENSION PERIOD 
Participation in the open extension period will only be offered to patients who participated in 
the comparative period of the study, did not withdraw prematurely from the latter and having 
given their free informed written consent to participate.
EXCLUSION CRITERIA: 
- Patients for whom no echocardiographic data are available. 
- Patients whose BNP is less than 100pg/ml or whose NT-proBNP is less than 300pg/ml 
- Patients suffering from a disease resulting in a life expectancy of less than 12 months 
(apart from heart failure). 
- Patients undergoing dialysis for kidney failure.  
- Patients with a heart transplant or a ventricular assistance device.  
- Inotrope-dependent patients. 
- Patients without the necessary autonomy to use the tele-cardiology equipment. 
- Patients participating in another therapeutic clinical trial. 
- Pregnant or breast-feeding women, or women of childbearing age not using an effective 
contraception method. 
- Patients under guardianship, wardship or placed under conservatorship 

 
 
 
 
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STATISTICAL ANALYSIS OF THE DATA: 
- The primary analysis will be performed using the intention-to-treat (ITT) principle. 
- Comparison of demographic and clinical data at inclusion in both arms. 
- Analysis of the primary efficacy criterion using Poisson regression model with adjustment 
to an offset variable equal to the duration of follow-up of each patient 
- Additional subgroup analyses according to sex, age, left ventricular ejection fraction, 
NYHA classification, telediastolic diameter value, number of patients recruited in each 
center and whether or not the patients have received therapeutic education and of the 
number of patients recruited in each center and the number of patients recruited in each 
center. 
- The number of readmissions for heart failure, the cumulative number of hospitalization 
days, the quality of life scores and the costs of management will also be analyzed as 
secondary objectives. 
 
- STUDY EXTENSION PERIOD  
The patients entering the extension period will be divided into two groups: 
- “Standard management / Tele-cardiology” group: patients from the “standard 
management” group of the comparative period entering the study extension period. 
- “Tele-cardiology / Tele-cardiology” group: patients from the “tele-cardiology” group of 
the comparative period entering the study extension period. 
 
All the analyses related to the patients participating in the study extension period will be 
presented by group (Standard management / Tele-cardiology vs. Tele-cardiology / Tele-
cardiology) and overall. 
SCHEDULED NUMBER OF CENTERS: 46 centers 
DURATION OF THE INCLUSION PERIOD: 42 months 
DURATION OF PARTICIPATION OF EACH PATIENT: 18 months 
An extension period using the monitoring by the tele-cardiology program will be offered to 
all patients who wish for this, until the tele-cardiology program is marketed.

 
 
 
 
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2. OVERALL DESCRIPTION AND RATIONALE OF THE STUDY IN THE LIGHT 
OF CURRENT KNOWLEDGE 
2.1. CURRENT STATE OF KNOWLEDGE 
2.1.1. HEART FAILURE 
 
Heart failure is defined as a disease of the cardiac pump causing a reduction in peripheral 
perfusion rates and oxygen supply to the perfused organs; it is the progressive form of the majority 
of cardiovascular disorders. A distinction is drawn between two major types of cardiopathy: so-
called ischemic (following coronary heart disease) and non-ischemic. Heart failure is characterized 
by repeated episodes of cardiac decompensation which lay the basis for multiple hospitalizations. It 
is characterized by progression towards either myocardial degeneration or serious ventricular 
arrhythmias leading to episodes of sudden death (1). The pathophysiology is essentially based on 
two major mechanisms, one related to hemodynamic changes (reduction in cardiac and peripheral 
perfusion) and the other corresponding to compensatory neurohumoral activation, the purpose of 
which is to ensure among other aspects peripheral perfusion rates. These changes partially explain 
the pattern of symptoms of heart failure patients which is classified either as signs of left, right or 
global heart failure or as major and minor criteria (2). 
Prevalence of heart failure has been constantly on the increase over the past twenty years, 
affecting 1 to 2% of the population in developed countries, essentially owing to the constant ageing 
of their populations (3, 4, 5). In France, it affects approximately 1 million individuals, representing 
2% of health expenses, more than 75% of which are related to hospitalizations. Heart failure was 
considered a public health problem by the preparatory group for definition of the national aims of 
the public health law of 2004. 
It is the primary cause of hospitalization after 60 years of age, in most cases unscheduled, 
contributing to congestion of the emergency services. Hence, in the U.S.A. (6, 7), it results in one 
million hospitalizations per year and the hospital admission rate for heart failure increased by 19% 
between 1990 and 1999 among the female population (8).  
 
 

 
 
 
 
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2.1.2. MANAGEMENT OF HEART FAILURE 
2.1.2.1. CURRENT MANAGEMENT 
 
Current management aims to improve quality of life by: 
- 
relieving the symptoms (shortness of breath, fatigue, edema, etc.); 
- 
allowing the activities of daily life; 
- 
preventing decompensation episodes and reducing the number and duration of 
hospitalizations; 
- 
delaying progression of the disease and reducing its mortality.  
 
Treatment of heart failure always involves:  
- 
non-drug treatment, with prescription of new dietary habits and regular physical activity; 
- 
well-codified and effective drug treatment for heart failure with demonstration performed 
based on the aforementioned criteria.  
 
Treatment with intracardiac devices (biventricular pacing) is playing an increasing role in heart 
failure that remains symptomatic despite optimum treatment. In case of an inadequate result, an 
indication for a left ventricular assist device or heart transplant is discussed in some patients. At a 
very advanced stage (NYHA refractory stage IV) palliative care should be offered (2).  
Therapeutic patient education (TPE) supplements the treatments (9). 
 
The combination of the constant increase in prevalence of heart failure owing to ageing of the 
population and the decrease in hospitalization capacity of our healthcare system (10) calls for 
development of outpatient management of these patients (11). It is responsible for 100,000 
hospitalizations per year in France, i.e. more than 5% of total hospital admissions and represents the 
primary cause of hospitalization of subjects of more than 65 years of age. The hospitalization period 
for heart failure is usually long, with the mean inpatient duration being around ten days in France 
with 2 to 3 hospitalizations per year, suggesting that the economic impact of this disease is therefore 
mainly related to repeated hospitalizations.  
A survey performed in Canada showed that owing to saturation of the downstream services, 35% of 
these patients leave the emergency service directly without any hospitalization in cardiology or 
geriatrics, which predisposes to early rehospitalizations (12). The rehospitalization rate is 
particularly high after an initial hospital admission for cardiac decompensation; 40% after 1 year on 
average (13, 14, 15). In Europe, in the EuroHeart Failure Study register where the patients were 

 
 
 
 
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included after hospitalization in a cardiology department, the rehospitalization rate is 24.2% after 3 
months (16). In the Canadian Alberta register (12) where a third of the patients leave the emergency 
service directly, the rehospitalization rate reaches 20% after one month and 60% after one year. 
The treatment can be further optimized, particularly in elderly subjects in whom beta blocking agents 
are underused (17, 18) in spite of the recommendations of the Cardiology and Geriatric Societies 
(19). Indeed, if beta blocking treatment has not been instituted within 90 days following 
hospitalization, there is little chance that it will be subsequently undertaken; as for the dosages, they 
are rarely increased during monitoring (20). Finally, the latest 2012 recommendations emphasize the 
value of broad prescription of mineralocorticosteroid antagonist receptors from stage II onwards 
(21), whereas their prescription currently only involves one third of patients (22, 23). 
The cost of this disorder based on the available sources of data derived from the routine databases, 
such as the PMSI and health insurance reimbursement data, estimate on the basis of 147,631 patients 
registered in LTD for a heart failure diagnosis that the amounts reimbursed by health insurance 
(outpatient and hospital expenditure) are around 1605 million Euros. Public hospital expenditure 
accounts for the first expense item (49.6%), with private hospital expenditure accounting for 10.6% 
of expenses. The economic burden of heart failure shows an upwards trend, since a 3.6% annual 
increase in LTD owing to heart failure is observed, highlighting the importance of implementing 
“avoidability” strategies.  
 
2.1.2.2. NEW MANAGEMENT STRATEGIES  
 
Global, multidisciplinary, coordinated management, including therapeutic education of heart 
failure patients has extensively shown its efficacy during recent years in reducing rehospitalization 
frequency (24, 25, 26, 27) and is currently recommended by the academic societies (28). Hence, in 
the meta analysis of 33 randomized, controlled studies by Roccaforte, the frequency of 
hospitalizations for all causes is reduced by 23% and that related to heart failure by 42% (29). 
Although the management methods vary from one study to another, the meta analysis by McAlister 
(30) shows that management based on home monitoring is more effective, particularly in elderly 
subjects with restricted mobility. Even though the benefit in terms of mortality is still less well 
established, with the latter showing a non-significant 15% decrease in the intervention arm of the 
COACH study which is the most extensive to date (31), this global management is recommended 
by all the academic societies (21, 28, 32). 
 

 
 
 
 
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Daily communication of weight and symptoms allows early detection of the first signs of clinical 
deterioration, resulting in intervention by the patient’s general practitioner (33, 34, 35, 36). It has in 
fact been demonstrated that the initial symptoms of worsening of heart failure occur 8 to 12 days 
before hospitalization (37) and measurement of thoracic impedance in patients wearing pacemakers 
reveals detects a reduction in this parameter, which is inversely correlated with pulmonary capillary 
pressures, 18 days on average before hospitalization (38). However, studies focusing on simple 
telephone management by a specialized nurse, which is readily accepted by patients, the majority 
of whom comply with this approach (39, 40), yielded contradictory results: this type of monitoring 
allowed a reduction in hospitalizations for heart failure and deaths in the DIAL study (41) and the 
trial conducted by Reigel (34) following a hospitalization for heart failure, but it did not have any 
effect in the study performed by DeBusk (42) focusing on less severe patients and did not reduce the 
hospitalization rates during a further two trials performed in the United States (WHARF study, 43) 
or in the Netherlands (44). 
 
Alongside this type of telephone supervision, telemonitoring methods have been more 
recently developed allowing passive recording of physiological data such as weight, blood pressure, 
heart rate and O2 saturation. In the TEN-HMS study, monitoring of these parameters by self-
measurement in the mornings and evenings resulted in a significant reduction in mortality versus 
standard management (35). Finally, telemonitoring methods “on board the patient” exist, with some 
defibrillator-resynchronizer manufacturers having equipped their bioimpedance measuring device 
box, measuring the water content of the chest (44, 45) or pulmonary pressures, but they currently 
remain restricted to patients who are candidates for electrical treatment of their heart failure. Using 
standard telephone lines, these new types of monitoring make it possible to overcome geographical 
barriers and therefore be accessible to the majority of patients (46). A pilot study (47) confirmed 
feasibility and safety of rapid return home. Following hospitalization for heart failure, patients 
receive home monitoring by a specialized nurse (48) who, assisted by a coordinating cardiologist, 
by means of “telemonitoring” incorporated in a structured telephone support system, thus presides 
over the outpatient care of heart failure patients (49). 
 
The most recent bibliographical data on this subject indicate however contradictory 
results. The last Cochrane meta analysis focusing on 25 studies, 11 assessing telemonitoring (2710 
patients), 16 assessing structured telephone supervision (5613 patients) and 2 assessing both these 
types of intervention, notes a significant 34% reduction in mortality owing to telemonitoring, 
whereas the 12% reduction observed with telephone monitoring does not achieve the degree of 

 
 
 
 
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significance, combined with a significant decrease in hospitalizations for heart failure of 31% and 
33% respectively under the effect of these two types of intervention (50). In the majority of the 
studies, both these methods are well accepted by patients and reduce healthcare costs (50). Since 
then however, the most extensive study (Tele-HF) focusing on telemonitoring has been published, 
finding neutral results (51). In this research, which included 1653 patients recently hospitalized for 
heart failure, daily telemonitoring of symptoms and weight did not modify, in comparison to usual 
treatment, the primary criterion combining death and rehospitalization, regardless of the cause after 
6 months, which occurred respectively in 52.3 and 51.5% of the patients or rehospitalizations (49.3% 
vs. 47.4%) (52). In this study however, 14% of the patients allocated to telemonitoring never used 
this system and at the end of follow-up, only 55% of the patients used it 3 times a week. These 
neutral results are reminiscent of those of two studies published in 2009. In the HHH study, which 
included 461 patients, weekly telemonitoring of vital signs (weight, heart rate, blood pressure, 
symptoms), whether or not combined with monthly monitoring of the ECG by a Holter system, did 
not show, after a 12 months’ follow-up, any significant effect on hospitalizations for heart failure or 
deaths versus usual treatments (53). In the Home-HF study, which included 182 patients hospitalized 
for heart failure, daily telemonitoring of weight, blood pressure, SaO2 and symptoms did not have 
any significant effect, after 6 months’ follow-up, on the number or duration of hospitalizations versus 
usual treatments (54). 
An analysis of these negative experiences makes it possible to put forward several 
explanations for these contradictory results (55, 56, 57, 58), which might originate, apart from 
underuse of the system by the patients: from the patients included and the recruiting centers who 
might not be representative of heart failure patients in the actual world (predominance of subjects 
originating from an urban environment, affluent socioprofessional category, least severely affected 
patients...), with optimum usual treatment of the patients in the control group testified by a 
particularly low annual mortality rate in these trials in relation to the cohort data; from the absence 
of inclusion of educational response in the telemonitoring systems; from monitoring of the alarms 
by personnel unskilled in managing heart failure patients; from an excessively short telemonitoring 
period, usually limited to 6 months in the previous studies (52). 
 
A new telemonitoring trial is therefore required that provides an answer to these various 
criticisms. 
Ultimately, development of this new form of managing a chronic disease could reduce the disparity 
in access to care throughout France and improve the prognosis of heart failure patients. This 

 
 
 
 
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approach calls for validation of the tools by a thorough methodological approach in the form of a 
clinical trial and structuring of a new care provision scheme. 
The management method studied, referred to in the protocol as the “tele-cardiology program” will 
therefore involve an alternative outpatient strategy in which the patients will receive personalized 
telephone support and supervision of their signs and symptoms at home by telemonitoring.  
Through communication of the data to all the players involved with the patient (referring physicians, 
general practitioner, cardiologist, privately practicing nurse...), this program will allow optimization 
of monitoring, particularly via a more rapid and more suitable response. 
2.2. HYPOTHESES OF THE RESEARCH AND ANTICIPATED RESULTS 
The patients’ profile, elderly with comorbidities and therefore with a high risk of dependency, 
influences the course of the disease and complicates management both in private practice and in 
hospital. The complexity of the patients’ medical and social circumstances and the two aims set by 
the 2004 law (improvement in patients’ quality of life and reduction in mortality and frequency of 
rehospitalizations) justify implementation of new healthcare organizations.  
The large number of players involved makes management complex. Tele-cardiology will 
encourage continuity of care as well as personalized and coordinated management, which are key 
factors in reducing the costs and improving the performance of our healthcare system. 
 
 
The OSICAT project objectives to demonstrate that such an approach is capable of influencing 
the following dimensions of management: 
 
Safety:  
This new healthcare strategy allows traceability of the procedures and prescriptions in addition to 
management of the alerts triggered. This safety issue is all the more important in the subjects 
concerned by the study, considered “fragile” and often presenting with atrial and ventricular cardiac 
arrhythmias, the main cause of sudden death in these patients (60, 61). 
 
Efficacy: 
Improvement in coordination of care and reinforcement of monitoring via telephone contact should 
allow an improvement in prevention and treatment compliance (short-term diuretics and long-term 
beta blockers) (62) and influence the incidence of undesirable effects and the progression of the 
complications of heart failure. 
 

 
 
 
 
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Motivation: 
The patient is involved in managing his/her chronic disease by regular information on the effects of 
his/her treatment and controlling his/her symptoms with an alert system that triggers establishment 
of contact with the Cordiva telephone telemonitoring center. 
It should promote development of PTE (31) and rehabilitation (63), which have demonstrated their 
benefit, particularly in terms of reducing the risk of rehospitalization (64), which is particularly high 
during this disorder, with 25% of patients being readmitted in Europe within twelve weeks following 
an initial hospitalization for acute heart failure (65). 
 
Organization of management: 
Use of the new information and communication technologies is a response to the discrepancy 
between care provision and a large population of patients suffering from cardiovascular 
comorbidities to be monitored in the long term. This entails development, validation and 
implementation of tools specifically developed in order to ensure optimum supervision at home.  
Beyond this remote management aid, the tele-cardiology program ensures that the patient is kept at 
home with independence and improvement in quality of life. This strategy is not only an effective 
means of reducing “avoidable” hospitalizations and their implications (costs, induced disorders, loss 
of independence or quality of life), but also of combating inequalities in access to healthcare. 
From the point of view of social acceptability by healthcare organizations and professionals 
and by patients, this study will allow identification of the success factors and potential sources of 
obstructions or constraints. Since healthcare systems are very rapidly changing and highly 
interdependent systems, the goal is to characterize the development processes in order to typify 
various different scenarios and characterize the conditions for successful enrolment (in the sense of 
Latour, 2006), on the one hand for the healthcare professionals directly involved and on the other 
hand for the patients and those contributing to management of their disease. 
This new management approach, based on coherent and coordinated relationships between the 
public and private sector and between healthcare professionals (general practitioners, privately 
practicing nurses, pharmacists and cardiologists...), focusing on patients and at their service, ought 
to bring about favorable developments in professional practices. 
 
Economy: 
The savings for the national health system will be measured in terms of gain or losses of 
hospitalization days valued by price per activity (T2A). 

 
 
 
 
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The difference in the mean inpatient period for heart failure between France, 10 days and other 
OECD countries, 4 days, suggests that another type of management is possible (59). This new 
structure ought to allow a reduction in the number of emergency hospitalizations for heart failure by 
acting on the upstream precipitating factors. 
  
This study will also help to determine a price of the remote telemonitoring device that is acceptable 
to society. 
We hypothesize that after 18 months, the patients will show a reduction of at least 30% in the 
primary criterion.  
2.3. BENEFIT / RISK RATIO 
Currently, standard management involves conventional monitoring during a consultation, with a 
visit to the general practitioner or referring cardiologist. Consequently, there is no loss of opportunity 
for the patients in the control arm, since this type of management by telemonitoring is not a standard 
management approach. This method of outpatient monitoring does not in principle incur any 
undesirable effects. The patient weighs him/herself and informs the device box provided and 
undergoes a telephone interview with the nurse from the call center every three weeks. 
We therefore consider the benefit/risk ratio of our project as favorable.  
2.4.  EXTENSION PERIOD 
The extension period will be conducted on an open, non-comparative basis. 
The aim of the extension period is to allow patients who wish to do so to follow the telemonitoring 
program until its marketing, regardless of the randomization group on initial inclusion in the study. 
Extension involves continuing the initial program, including personalized telephone support and 
home telemonitoring supervision in order to optimize patient management, particularly via a more 
rapid and more appropriate response. 
 
3. OBJECTIVES OF THE STUDY 
3.1. PRIMARY OBJECTIVES 
To assess the impact of a tele-cardiology program on morbidity-mortality in heart failure patients 
versus standard monitoring. 

 
 
 
 
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3.2. SECONDARY OBJECTIVES 
 
1) To assess the effect of management by tele-cardiology versus standard management on 
hospitalizations and deaths of cardiovascular origin.  
 
2) To compare the kinetics of evolution in quality of life between day 0 and month 18 in the 2 
groups.  
 
3) To assess the differential cost-efficacy and cost-utility ratios of both patient management 
strategies. 
 
4) To assess societal acceptability of management by tele-cardiology among healthcare 
professionals and patients. 
 
5) To collect data concerning the hospitalizations and deaths during the extension period of the 
tele-cardiology program among the patients who wished to participate in the latter. 
 
 
 

 
 
 
 
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Investigational objectives  
Exploratory study to allow for the complementary development of algorithms for generating alerts. 
3.3. ASSESSMENT CRITERIA  
The study assessment criteria will be recorded, regardless of the patient’s randomization arm, firstly 
through the telephone contacts established by a clinical research technician at 0, 6, 12 and 18 
months and secondly by means of the anonymized hospitalization reports. 
 
The investigators will determine the cardiovascular origin or not of the deaths and the 
hospitalizations and the programmed or not programmed of the hospitalizations. The investigators 
will determine the cardiovascular origin or not of the deaths and the hospitalizations and the 
programmed or not programmed of the hospitalizations. 
 
A panel of experts will meet at the end of the study. The meeting will be prepared beforehand by the 
sponsor. The aim of this study will be to validate occurrence of the events forming the main criterion 
and the secondary criteria in order to ensure their proper listing (adjudication committee). This 
committee will determine, on a blind basis, the relevance and the reasons for the hospitalizations 
(cardiovascular or other) and deaths and the programmed or unplanned nature of hospitalizations. It 
will be formed of physicians who are not involved in the study and who are not aware of the arm to 
which the patients are assigned. The adjudication committee will be chaired by a methodologist of 
the study, Dr. Ruidavets or Professor Bongard.  
 
3.3.1. PRIMARY ASSESSMENT CRITERION 
The primary assessment criterion is a composite criterion combining the number of unplanned 
hospitalizations for any cause and death from any cause during the 18-month comparative period in 
both groups. 
3.3.2.  SECONDARY ASSESSMENT CRITERIA 
 
1) Comparison of the number of events (deaths and hospitalizations of cardiovascular origin) 
between the 2 groups after 18 months. 
2) Comparison of the means of the Short Form-36 (SF-36) quality of life scale scores in the 2 groups, 
at inclusion and at 18 months.  

 
 
 
 
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3) Measurement of the annual cost of treatment in both groups from the point of view of the hospital 
and the health insurance scheme. 
4) Measurement of the social acceptability of the tele-cardiology program for patients and healthcare 
professionals 
5) Annualized numbers of hospitalizations for any cause, and numbers of deaths from any cause 
occurring during the extension period for the patients who wished to participate in the latter. 
6) Annualized numbers of hospitalizations and numbers of deaths of cardiovascular origin occurring 
during the extension period for the patients who wished to participate in the latter. 
 
 

 
 
 
 
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4. Experimental design 
 
The OSICAT project consists of a comparative, randomized, 18-month period followed by a non-
comparative extension period for patients from the first period who wished to participate in the latter. 
4.1. OVERALL STUDY DESIGN 
This study is : 
- 
comparative (management by tele-cardiology versus standard management) 
- 
2 parallel groups.  
- 
randomized ratio (2: 2)  
- 
open-label 
- 
in chronic heart failure patients 
- 
multicentric 
- 
national 
 
It is scheduled to recruit a total of 990 patients over a three-year period in 46 participating centers. 
This study comprises an inclusion visit with the investigating cardiologist followed by 4 telephone 
contacts by Clinical Study Technicians (CST). No hospitalization is scheduled during the study. 
4.2. RANDOMIZATION 
Randomization and allocation of a patient identifier for the duration of the study will be performed 
by computerized means via the eCRF during the patient inclusion visit.  
Each patient will be assigned to one of the two study arms via random drawing of lots. 
Randomization will be centralized and set up for each institution participating in the study. Not being 
aware at the outset of the patient recruitment potential for each center, it was decided to perform a 
random draw according to a randomization scheme in a balance block of four patients (allocation 
ratio 2: 2) to make it easier to obtain comparable cohorts between the two study arms for each 
participating center. The randomization list will be pre-established for each center and for the entire 
cohort to be recruited.  
The patients in the control arm will undergo conventional monitoring, involving return home with 
monitoring during consultation with their general practitioners or referring cardiologists. 
This study will be performed with an open label: the patients and all the persons involved (nurses, 
referring physicians, CST) will be informed of the randomization arm allocated. 

 
 
 
 
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In order to limit data bias, the adjudication committee will assess the relevance of the hospitalizations 
on a blind basis. 
 
4.3. STUDY SCHEDULE 
The patients in the control arm will undergo conventional monitoring, involving return home with 
monitoring during consultation with their general practitioners or referring cardiologists. 
  
The patients in the tele-cardiology arm will receive the equipment necessary for their monitoring at 
their homes during the week following their inclusion visit, comprising a communicating electronic 
balance and a box for answering the questionnaire assessing the progressiveness of their symptoms. 
During presentation of the study schedule to the patient, before inclusion, the investigating physician 
will show him/her the equipment to be used. 
The equipment provided is “auto-installable”, but if the patient deems necessary, the equipment will 
be installed at the patient’s home by privately practicing nurses. They will also need to ensure that 
the patients know how to use it. 
Each patient will answer 8 simple questions every day: 
- Did you experience breathing disorders last night that were more severe than during the 
previous night? 
Inclusion of 990 heart failure patients by 46 cardiology centers in France 
 
Randomization
(distribution into the groups by random selection) 
Group 1 
(495 patients) 
“Standard” 
management 
Group 2 
(495 patients) 
Management by 
management 
Tele-cardiology 
Program 
Self-measurement at home 
communicating box and 
CORDIVA  
Personalized support center 
telephone monitoring by an 
advisory nurse 
Telephone questionnaires by a Clinical Study Technician
15 days 
6 months 
12 months 
18 months 

 
 
 
 
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- Did you need an additional pillow last night in order to breathe more easily? 
- Are you coughing more often than usual? 
- Are your legs more swollen than usual? 
- Do you feel more tired today? 
- Have you had, or do you have fever of more than 38.5°C?  
- Have you experienced or are you experiencing palpitations?   
- Do you find that your physical activity is more restricted today than on previous days? 
The patients will be required to answer simply yes/no to all these questions using the device box. 
The self-monitoring parameters (weight and answers to the questionnaire) will be remotely 
transmitted via standard telephone lines (landline, 3G or GPRS) to the secure server.  
These data will be analyzed automatically by an expert system that will generate an alert in case of 
abnormal values, with the aim being to forestall any cardiac decompensation. 
The specialized nurses at the Cordiva telephone monitoring center will have access to the alert on 
working days and must contact the patient in order to check with him/her the relevance of the alert.  
If the clinical genuineness of the alert is validated, she will advise him/her to contact his/her general 
practitioner or referring cardiologist. In parallel, the referring physician will have access to a report 
including weight progression and the patient’s symptoms that triggered this alert. Consequently, s/he 
will be able to implement the measures that s/he considers appropriate.  
 
An information folder will be sent to the patients. (Appendix no. 1). It contains a number of elements 
of information relating to management of his/her heart failure: physiology of the heart, symptoms of 
the disease, treatments and dietary and lifestyle rules... 
The aim of this folder is to assist exchange concerning specific topics between the Cordiva nurse 
and the patient. 
 
As soon as the equipment has been received and installed in the patients’ homes, the specialized 
nurses will conduct an initial telephone interview that will last approximately 45 minutes. It will 
initially allow the nurse to introduce the team and the approach and get to know the patient better 
(medical history, treatments, psychosocial profile, tobacco and alcohol consumption, physical 
activity, etc.). 
Following this call, the patient and nurse will jointly determine the date of the next phone contact. 

 
 
 
 
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During the comparative period, a nurse from the Cordiva telephone monitoring center will contact 
the patient every 3 weeks to ensure his/her proper understanding of his/her illness and treatment and 
to assist him/her in managing his/her illness in daily life (compliance, performance of physical 
exercise, dietary hygiene, experience of the disease...). This call will last 15 minutes on average, but 
is not limited; the duration is defined depending on the patient's needs. 
Following each telephone contact, the nurse will establish educational aims in conjunction with the 
patient (knowledge of the disease, of the medications, recognition of the signs of cardiac 
decompensation, adoption of good dietary habits, performance of regular physical activity).  
The support center will also be available for incoming calls from the patients, who will thus be able 
to easily contact a specialized nurse from the Cordiva center 5 days a week on working days. This 
telephone line does not manage emergencies and will not be a substitute for dialing 15, with the 
emergency department remaining the principal contact person in case of a vital emergency. 
 
If the patient leaves home temporarily (for a vacation for example), s/he will be able to take the reply 
box and scales with him/her. Since this equipment is fitted with a GSM chip, it will be possible to 
continue to record the patient’s data. The patient will also be able to provide another telephone 
number for the interviews with the nurses. 
 
The patient’s general practitioner will be involved in this outpatient management from the outset. 
Indeed, the data collected by means of the scales and box will allow drafting of reports on the 
progression of his/her patient’s symptoms. These reports will be communicated to him/her every 
2 months. These reports will also be sent to the referring cardiologist. 
Furthermore, in case of a validated alert, the referring physician will have access to a report on the 
progression of weight and symptoms, thereby allowing him/her to take any measures that s/he deems 
appropriate. 
 
THE CORDIVA CENTER  
Nurses specializing in management of heart failure in addition to therapeutic education, owing to 
the specific training programs that they have been able to follow, will form the backbone of the team. 
Indeed, the many experiments conducted in multidisciplinary management of heart failure patients 
have proven the key role of specialized nurses who establish a link between the patients and the 
different healthcare players (67, 68, 69, 70). 

 
 
 
 
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They will supervise application of the instructions of the referring cardiologist and the general 
practitioner and will ensure monitoring of the patients’ clinical parameters (weight and symptoms).  
They will have an interview guide at their disposal. Objective elements (state of health, clinical signs 
and medications) will be collected and entered in a computerized file. 
It should be noted that these data will be requested strictly with a view to supporting the patient and 
will therefore not appear in the trial. Provision is made during patient follow-up for strict separation 
of the circuits between the data collected by the nurses and those recovered by the CST for the study 
(the latter will only be used to judge the main assessment criterion). 
Concerning assessment of the patients’ knowledge and needs, the nurses will use active listening 
methods (open questions, reformulation, empathy and positive reinforcement).  
These methods encourage study of the patient’s knowledge of his/her disorder and his/her treatment 
in order to personalize the information to be conveyed. 
The nurses at the Cordiva center have undergone specialized training in conducting the motivational 
interview. 
The nurses from the Cordiva center have also received other training in cardiology and heart failure, 
“psychic status” of heart failure patients, communication and therapeutic education. 
Given the absence of validating training in personalized support in chronic disease, the nurses 
received in the absence thereof validating training in therapeutic education.  
The homogeneity of this informative approach is guaranteed on the one hand by the tools available 
to the nurses (folder, interview guide) and on the other hand by the intrinsic functioning of the 
personalized support center (patient monitoring performed by a team of nurses, weekly debriefing 
of some interviews recorded on the principle of the staffs in the departments and unity of place...). 
4.4. STUDY EXTENSION PERIOD 
 
All the patients who were included in the comparative period will be contacted to propose an 
appointment with the investigating physician. During this appointment, the investigating physician 
will present continuation of the monitoring of the tele-cardiology program.  
 
The patients who accept to participate in the extension period will sign an informed consent form 
for this period. 
The patients in the tele-cardiology program monitoring group will keep the telemonitoring 
equipment. 

 
 
 
 
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The patients in the standard monitoring group wishing to undergo the monitoring of the tele-
cardiology program will be equipped and monitored as described in paragraph 4.3, based on the visit 
for entry into the extension period. 
Feedback of the self-monitoring data (weight and 8 questions) in addition to management of the 
alerts will be identical to those in the comparative period.  
During the extension period, the frequency of the calls by the Cordiva telephone monitoring nurse 
can be personalized depending on the patient’s needs. At least 1 call every 8 weeks must be made. 
 
5. ELIGIBILITY CRITERIA 
5.1. INCLUSION CRITERIA 
- 
Men or women of 18 years of age and older.  
- 
Heart failure patients having been hospitalized for cardiac decompensation during the past 
12 months 
- 
Patients having a landline telephone or with access to the GPRS network at their homes 
- 
Patients having given their free informed written consent to participate in the study 
- 
Patients subscribing to a social insurance scheme  
5.2. EXCLUSION CRITERIA 
- 
Patients for whom no echocardiographic data are available. 
- 
Patients whose BNP is less than 100pg/ml or whose NT-proBNP is less than 300pg/ml 
- 
Patients suffering from a disease resulting in a life expectancy of less than 12 months (apart from 
heart failure). 
- 
Patients undergoing dialysis for kidney failure.  
- 
Patients with a heart transplant or a ventricular assistance device.  
- 
Inotrope-dependent patients. 
- 
Patients without the necessary autonomy to use the tele-cardiology equipment. 
- 
Patients participating in another therapeutic clinical trial. 
- 
Pregnant or breast-feeding women, or women of childbearing age not using an effective 
contraception method. 
- 
Patients under guardianship, wardship or placed under conservatorship  

 
 
 
 
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5.3. RECRUITMENT METHODS 
Recruitment will be performed prospectively based on the cardiology consultations of the centers 
participating in the study or following hospitalization for cardiac decompensation. During these 
consultations, the patients will receive the information concerning the study and will be allowed a 
consideration period.  
The different centers have undertaken to perform the following recruitment: 
- Toulouse Teaching Hospital Center: 10 patients per month; 
- Val d'Ariège Hospital Center Foix-Pamiers: 4 patients per month; 
- Rodez General Hospital Center: 4 patients per month; 
- Auch General Hospital Center: 4 patients per month; 
- Castres-Mazamet Intercommunal Hospital Center: 4 patients per month; 
- Pont de Chaume Clinic: 4 patients per month; 
- Joseph Ducuing Hospital: 10 patients per month; 
- Union Clinic: 8 patients per month; 
- Figeac Hospital Center: 4 patients per month; 
- Midi Gascogne Center (formerly called Beaumont de Lomagne Aftercare and 
Rehabilitation): 5 patients per month; 
- Ormeau Clinic: 5 patients per month. 
 
For each patient, the treating physician will be informed of his/her participation in this study, in 
addition to the extension period, if the patient has accepted the latter.  
5.4. INCLUSION CRITERIA DURING THE EXTENSION PERIOD 
Participation in the open extension period will only be offered to patients who participated in the 
comparative period of the study, did not withdraw prematurely from the latter and having given their 
free informed written consent to participate. 
 

 
 
 
 
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6. MANAGEMENT OF THE TELEMONITORING EQUIPMENT 
6.1. SUPPLY OF THE EQUIPMENT 
The equipment consists of: 
- 
communicating scales (model: A&D Medical Precision Health Scale UC-321) via bluetooth; 
- 
A communicating box (model: Tunstall RTX 3371) via landline network or GSM (SIM card 
inserted into each box).  
NB: these items of equipment are not considered medical devices and consequently, they are not 
distributed by a laboratory or pharmacy. They can be replaced by equivalent devices during the 
study. 
The equipment is supplied by the company CDM e-Health.  
Following the first call to the patients, the specialized nurses of the monitoring center issue an order 
for dispatch of the equipment to the patient in question. 
 
6.2. PACKING OF THE EQUIPMENT 
The scales and box are packed in two separate cartons.  
Once the equipment dispatch order has been issued, a configuration phase of the SIM card inserted 
in the box is performed by the CDM e-Health IT department. 
These 2 items of equipment are subsequently packed in a single carton by the specialized nurses of 
the CDM e-Health monitoring center. 
 
6.3. LABELING OF THE EQUIPMENT 
Labeling of the equipment itself (e.g.: batch no.) is performed by the respective manufacturers of the 
scales and the box. 
The cartons dispatched to the patients are labeled by the specialized nurses from the monitoring 
center. 
6.4. DISPATCH AND MANAGEMENT OF THE EQUIPMENT 
As stated above, dispatch of the consignments is ordered by the specialized nurses from the 
monitoring center. Dispatch is subsequently performed by registered mail with handing over against 
a signature. 

 
 
 
 
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ASS and management of technical incidents are provided by the CDM e-Health IT department (a 
free phone number is made available to the patients).  
6.5. MANAGEMENT OF THE TELEMONITORING EQUIPMENT DURING THE 
EXTENSION PERIOD 
The same procedures and principles will be applied as during the comparative period, referring to 
sections 6.1, 6.2., 6.3 and 6.4  
7. CONCOMITANT TREATMENT(S) AND PROCEDURE(S) 
7.1. AUTHORIZED CONCOMITANT TREATMENT(S)/PROCEDURE(S) 
All former treatments and treatment modifications are allowed. 
7.2. FORBIDDEN CONCOMITANT TREATMENT(S)/PROCEDURE(S) 
Whether or not prior therapeutic education has been received does not represent an inclusion or 
exclusion factor within the context of this study. Following their inclusion, patients never having 
received therapeutic education may, furthermore, participate in one of these programs without 
resulting in withdrawal from the study. 
During their participation in the OSICAT study, the patients will not be able to take part in another 
research protocol. If they nevertheless wish to be incorporated in another protocol and if this is in 
their interest with regard to the disease, they will initially be required to undergo an OSICAT study 
withdrawal visit. 
 
8. DESCRIPTION OF THE MEDICO-ECONOMIC ASSESSMENT 
A cost-efficacy-type analysis will be performed. Its aim will be to assess the differential cost-efficacy 
ratio of two management strategies for patients presenting with chronic heart failure: monitoring by 
telemonitoring management versus conventional management. The medico-economic data will be 
collected every 6 months (between M6 and M18) via a telephone interview. 
This study will allow establishment of a link between the costs and medical consequences expressed 
in terms of overall survival at 18 months for the patients of both management strategies. 
A supplementary cost-utility analysis will be performed. 

 
 
 
 
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8.1. EFFICACY ANALYSIS 
The efficacy criterion will be overall survival at 18 months, in accordance with the assessment 
criterion of the clinical study. 
8.2. UTILITY ANALYSIS 
The utility criterion will be overall survival at 18 months, the assessment criterion of the clinical 
study, weighted by the patients’ quality of life. Quality of life will be assessed using the SF36 
questionnaire (71). The latter is a multidimensional, generic, validated scale in French, which can 
be administered by as a self-questionnaire or hetero-questionnaire. Its 36 items assess 8 dimensions: 
physical activity, limitations due to physical condition, physical pains, perceived health, vitality, life 
in relationship with others and limitations due to physical status and psychic health, in addition to a 
specific dimension, i.e. assessment of perceived health versus one year previously. 
8.3.  COST ANALYSIS 
8.3.1. STANDPOINT ADOPTED 
The costs will be assessed from the point of view of the payer, health insurance and society. The 
costs considered will be direct medical and non-medical costs as well as indirect costs. Intangible 
costs related to pain, anxiety, loss of wellbeing and quality of life will not be assessed. 
 
8.3.2. COST CATEGORIES 
The costs taken into account will group together the costs of managing patients presenting with acute 
heart failure within the context of each of the two management strategies: telemonitoring versus 
conventional monitoring. They will include the costs of management associated with the 
hospitalizations, outpatient care, drug treatments, transport and with the nurses providing home 
monitoring of the patients and of the telemonitoring device (72). Furthermore, costs related to 
informal support (i.e. that provided by close relatives) and costs related to loss of productivity (i.e. 
indirect costs) will also be assessed (73). The expenses incurred by management of the 350 patients 
in each of the arms, i.e. 700 patients all in all, will be recorded over an 18-month period. A 
measurement of the physical quantities of resources consumed and a monetary valuation of these 
resources will be performed. 
 

 
 
 
 
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8.3.3. RECORDING OF THE COSTS 
Given the number of patients included and the number of institutions from the Midi-Pyrenees region 
participating in the protocol, the data will be collected from the Regional Health Insurance Fund 
(CRAM) for the patients falling under the General Scheme for Employed Workers (RGTS), from 
the Agricultural Mutual Benefit Society schemes (MSA) for farmers and from the Social Security 
Scheme for Self-employed Workers (RSI) for patients falling under this scheme. The List Enrolment 
Number (NIR) used by the health insurance organizations to identify patients will not be used as an 
identification code for the patients included in the study. The patients will be identified by their 
name, first name, date of birth and postcode of their place of residence. 
Data relating to hospitalizations will be collected directly from the participating centers.  
Data concerning the informal support provided by the patient’s close relatives will be recorded using 
a questionnaire. These data will be collected at 6, 12 and 18 months. 
 
8.3.4. VALUATION OF THE COSTS 
Valuation of the indirect costs 
The costs of the inpatient stays will be valued based on the framework defined by Pricing per 
Activity (T2A). The inpatient stays associated with management of the patients in each of the 
participating centers and any complications will be valued based on the rates of the Uniform 
Hospitalization Groups (UHG) corresponding to the Uniform Patient Groups (UPG) plus any 
supplements envisaged within this context (resuscitations, intensive care, ...). Hence, the inpatient 
stays corresponding to management of acute heart failure will be valued based on the UHG and the 
supplements of the corresponding UPG. Likewise, the inpatient stays for management of 
complications will be valued based on the UHG and the supplements of the corresponding UPG 
(74). 
The costs of the ambulant care provided in privately practicing medicine or in a public or private 
sector healthcare institution will be identified and value based on the pricing applied by Healthcare 
Insurance. The rates of the Common Classification of Medical Procedures (CCMP) and of the 
Nomenclature of Medical Biology Procedures (NMBP) will be applied (75). 
The transport costs will be valued taking account of the distance between the patient’s place of 
residence and his/her place of treatment in addition to the means of transport used. The rate 
recognized by Healthcare Insurance according to the means of transport used (ambulance, light 
medical vehicle (LMV), taxi, train or private car) will be applied (76). 

 
 
 
 
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The costs related to informal support will be valued using the replacement costs approach. This 
approach involves valuing the time spent for informal support provided by close relatives using the 
hourly rate of a close substitute (e.g. hourly wage of a home help) (73). 
 
Valuation of the indirect costs 
The costs related to loss of productivity will be valued based on the daily indemnities paid by 
healthcare insurance for absences from the workplace owing to illness (77). 
 
Valuation of the costs of telemonitoring the patients at home 
Account will be taken of the costs of telemonitoring the patients at home by the specialized nurses. 
They will be valued based on the time periods spent by the nurses in monitoring the patients’ clinical 
parameters, in applying the instructions of the referring cardiologist and of the general practitioner 
and in conducting therapeutic education as part of outpatient management of the patients and based 
on the hourly cost including the expenses of this personnel.  
 
Valuation of the cost of the remote telemonitoring device 
The cost of the remote telemonitoring device must be taken into account.  
The sponsor, as the company supplying the technical telemonitoring device, must submit a 
theoretical sales price. 
8.4. COST-EFFICACY ANALYSIS 
A cost-efficacy-type analysis will be performed. This type of study will allow establishment of a 
link between the costs and medical consequences expressed in terms of overall survival at 18 months 
for the patients of both management strategies. The differential cost-efficacy ratio of supervision by 
telemonitoring versus conventional monitoring will be calculated. It will make it possible to identify 
a preference between the two strategies. 
8.5. COST-UTILITY ANALYSIS 
The cost-efficacy study will be supplemented by a cost-utility analysis. It will establish a link 
between the costs and medical consequences expressed in terms of overall survival at 18 months 
weighted by the quality of life of the patients of both management strategies (QALY). In order to 
obtain transformation of quality of life into QALY, we will use the utility function offered by the 
company Qualitymetric©(78). The differential cost-utility ratio of supervision by telemonitoring 

 
 
 
 
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versus conventional monitoring will be calculated. This ratio will make it possible to identify a 
preference between the two strategies. 
8.6. DATA UPDATE 
No update of the costs, efficacy and quality of life will be performed. Update, which involves taking 
account of the individuals’ preference is not justified for the moment owing to the monitoring period 
limited to 18 months in the clinical study (72). 
8.7. SENSITIVITY ANALYSIS 
In order to test robustness of the results of comparison of the 2 management strategies, a multivariate 
sensitivity analysis will be performed by varying the parameters of efficacy, quality of life and costs. 
The cost of the remote telemonitoring device will in particular be taken into account (72). 
9. DESCRIPTION OF ASSESSMENT OF SOCIETAL ACCEPTABILITY 
Societal acceptance for patients on the one hand and for professionals on the other hand will be 
studied by means of semi-structured interviews according to the referenced methods (79, 80). These 
interviews will be conducted in person, at the patient’s home and at the professionals’ workplace. 
They will be supplemented periodically by observations in the participating healthcare institutions. 
The interview grid for the patients (who may if they wish be met with an accompanying person) will 
be of the “sociology of practices” type, focusing on living with the disease on a day-to-day basis, on 
practice of telemonitoring and its integration in the various medical, care and monitoring 
interventions.   
The grid for interviewing the professionals will be centered on the practicalities for integrating the 
telemonitoring device in medical management and more generally, in care and on the coordination 
measures required within and between organizations. A more specific derivation of the grid will be 
adapted to each profession. 
An initial wave of analysis will be performed after conducting some twenty interviews among the 
patients on the one hand and among the different groups of professionals on the other hand, in order 
to adjust the interview grid if necessary and select focuses to be studied in further depth. The value 
of a comprehensive qualitative approach precisely lies in allowing an analysis by stages, with gradual 
adjustment of the grid in order to incorporate aspects identified as important during the very process 
of investigation and analysis. 
Selection of the dialogue partners will be based: 

 
 
 
 
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- in the case of the professionals, on an initial mapping of the institutions, drafted during the 
first stage of the study on this constituent; 
- in the case of the patients, based on a selection of socioeconomic, cultural and life history 
criteria.  
A significant sample will be compiled: in the qualitative approach, the sample does not aim at 
representativeness, but instead a distribution of the situations that are relevant with regard to the 
questions to be dealt with (79, 81, 82). This sample should make it possible to reflect the variety of 
situations in terms of training levels, socioprofessional categories, income levels and living 
environments (including urban/rural). 
The following number of interviews is scheduled: 
- 
80 interviews with the patients  
- 
30 interviews with the treating physicians 
- 
40 interviews with the cardiologists: firstly, in the hospital institutions involved in the study and 
secondly those monitoring the patients outside hospitalization periods. 
- 
30 interviews with emergency physicians (since even if they are not stakeholders in our research 
in compiling the sample, they are often the point of entry of the patients in “ordinary” mode. It 
is therefore important to specifically identify the conditions capable of facilitating their eventual 
enrolment in the service).  
- 
30 interviews with the privately practicing nurses. 
These semi-structed interviews lasting one hour will be conducted: 
 during the first months of implementing the service (once the very first weeks of adoption). 
 one year after start-up 
 at the end of the research, at 18 months. 
1/3 of these interviews will be conducted among a stable subset of dialogue partners in order to 
identify any changes in duration. 
Choosing a longitudinal perspective is particularly important in order to characterize the progress 
stages and specifically identify the matters at stake, which often become apparent over time. 
Subsequent questioning alone would raise major risks of reformulation in the light of the final 
assessment of the device. 
 
For the case studies of organizational practices and their development, observations will be 
performed in hospital departments associated with the research in order to apprehend fully the way 
in which process of managing the patients is conducted, from their admission onwards, but also their 
entire progress within the institution (this observation of professional practices will obviously not 

 
 
 
 
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apply to the personal discussions with the patient) and thus perceive the way in which this new 
management method can be integrated in the processes already in place. 
Both the interviews and observations will be performed subject to the consent of the persons in 
question. The data collected will be anonymized, which the knowledge that this information will 
focus on the practices, associated changes and the social and professional issues. 
 
Assessment criteria for societal acceptability:  
- Characterization of the scenarios and factors promoting or hindering societal acceptability of 
management by telemonitoring in the patients and of the elements comprising their living 
environment. 
- Characterization of the scenarios and factors promoting or hindering acceptability of management 
by telemonitoring among the healthcare professionals and organizations concerned by this 
management. 
The study objectives to identify the conditions promoting the success of this new sociotechnical 
scheme and those that may represent obstacles or impediments, both on the part of the healthcare 
organizations and professionals and on the part of the patients. It falls within a longitudinal 
perspective in order to characterize the progress stages and specifically identify the matters at stake, 
which often become apparent over time. Model scenarios, categories of situations and factors will 
be produced in order to characterize this acceptability. 
10. RESEARCH SCHEDULE 
10.1. RESEARCH CALENDAR 
- Start of inclusions: 2nd quarter of 2013 
- Duration of the inclusion period: 42 months 
- Duration of participation of each patient: 18 months 
- Total duration of the research for the comparative period: 5 years  
- Duration of the extension period: until marketing of the tele-cardiology program 

 
 
 
 
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10.2. SUMMARY TABLE OF PATIENT MONITORING 
 
Inclusion 
D0 
Telephone 
visit 1 
Month 0  
(+/- 15 days) 
Telephone 
visit 2 
Month 6 
(+/- 15 days) 
Telephone 
visit 3 
Month 12 
(+/- 15 days) 
Telephone 
visit 4 or end 
of study visit 
Month 18 
(+/- 15 days) 
Extension 
period until 
marketing of 
the tele-
cardiology 
program  
Informed consent 
 
 
 
 
 
 
Inclusion/exclusion criteria 
 
 
 
 
 
 
Demographic data1 
 
 
 
 
 
 
Clinical examination 
 
 
 
 
 
 
Recording of history  
 
 
 
 
 
 
Concomitant treatments 
 
 
 
 
 
 
Randomization 
 
 
 
 
 
 
Main assessment criterion 
 
 
 
 
 
 
SF36 
 
 
 
 
 
 
Medico-economic questionnaire 
 
 
 
 
 
 
Adverse events 
 
 
 
 
 
 
Vital status 
 
 
 
 
 
 
Semi-structured interviews and observations for health organization case studies 
 
Patient societal acceptability 
 
 
 
 
 
 
Healthcare professional societal 
acceptability interviews
 
 
 
 
 
 
Observation of the participating 
hospital institutions 
 
 
 
 
 
 
1Demographic data: Date and place of birth, sex, contact details 
 
10.3. INCLUSION VISIT 
The inclusion visit is performed by the investigating physician. Before any examination related to 
the research, the investigator obtains the patient’s free, informed, written consent. 
 
 

 
 
 
 
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OBTAINING OF CONSENT 
During the inclusion visit, the investigating physician informs the patient and answers all his/her 
questions concerning the aim, nature of the constraints, foreseeable risks and anticipated benefits of 
the research. S/he also states the patient's rights within the context of biomedical research and checks 
the eligibility criteria. The investigating physician subsequently issues the patient a copy of the 
information note and informed consent. 
The investigating physician is responsible for obtaining the patient's written informed consent. The 
consent form must be signed before performing any clinical or paraclinical examinations required 
by the research.  
 
If the patient gives his/her consent to participate, the patient and the investigator write their names 
and first names in plain text before dating and signing the consent form. 
The different copies of the information note and consent form are subsequently distributed as 
follows: 
- A copy of the information note and signed consent is issued to the patient. 
- The original copy is kept by the investigating physician (even if the patient changes address 
during the research period) in a safe place inaccessible to third parties. 
- At the end of the inclusions or on completion of the research at the latest, a copy of each 
consent form is forwarded to the sponsor or to the latter’s representative according to the 
practicalities communicated in due course to the investigators. 
 
OBTAINING OF CONSENT FOR THE EXTENSION PERIOD 
During the visit for entering the extension period, the investigating physician informs the patient and 
answers all his/her questions concerning this extension period of the tele-cardiology program. 
The investigating physician subsequently issues the patient a copy of the information note and 
informed consent. 
The investigating physician is responsible for obtaining the patient's written informed consent. 
 
If the patient gives his/her consent to participate, the patient and the investigating physician write 
their names and first names in plain text before dating and signing the consent form. 

 
 
 
 
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The different copies of the information note and consent form are subsequently distributed as 
follows: 
- A copy of the information note and signed consent is issued to the patient. 
- The original copy is kept by the investigating physician in a safe place inaccessible to third 
parties. 
- At the end of the extension period, a copy of each consent form is forwarded to the sponsor 
or to the latter’s representative according to the practicalities communicated in due course to 
the investigating physicians. 
 
INCLUSION ASSESSMENT: 
 
During the inclusion visit, the investigating physician of each center must ensure that the inclusion 
criteria are fulfilled and that no exclusion criteria are present.  
 
During this initial visit, the demographic data (date and place of birth, sex), the patients’ history and 
concomitant treatments and the presence of risk factors (heredity, tobacco, dyslipidemia) will be 
collected and a clinical examination will be performed. 
The clinical examination will include: 
- Measurement of weight and height, 
- NYHA class assessment,  
- assessment of the presence of chronic kidney disease, COPD, a coronary disorder, arterial 
hypertension or diabetes mellitus, 
- measurement of arterial blood pressure and heart rate, 
The investigator must specify whether the patient presents with left, right or global heart failure and 
whether ischemic or non-ischemic cardiopathy is involved. 
During this initial visit, the patient must submit a laboratory assessment dating back less than 
3 months comprising measurement of potassium, blood urea and creatininemia. A measurement of 
telediastolic diameter and left ventricular ejection by echocardiography according to the Simpson 
Biplan method must also have been performed within the past 12 months.  
 
If the patient has already followed a therapeutic education program corresponding to the definition 
below, the date of this education must be stated. 

 
 
 
 
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According to the WHO, “therapeutic education for patients is intended to help patients acquire or 
maintain the skills they need to optimally manage living with a chronic disease. It is an integral and 
continuing part of patient care. It comprises organized activities, including psychosocial support, 
designed to make patients aware of and inform about their disease and about health care, hospital 
organization and procedures, and behavior related to health and disease, so that they (and their 
families) understand their disease and their treatment, collaborate with each other and take 
responsibility for their own care as a means of maintaining or improving their quality of life.  Oral 
or written information and advice on prevention may be given by a healthcare professional on a 
number of occasions, but are not equivalent to therapeutic education of the patient” (83). 
 
Following this visit, the patients will be randomized to two arms (centralized and computerized 
randomization): 
- one supervised on an outpatient basis by telemonitoring (so-called “telemonitoring arm”) 
comprising daily measurement of weight, daily collection of a self-declaration of symptoms and 
personalized educational enhancement by the specialized nurses of the CDM e-Health monitoring 
center;  
- the other monitored conventionally (so-called “control arm”). 
 
In order to perform randomization, the investigator will need to connect to the secure site hosting 
the online eCRF using a personal identifier and a password known to him/her alone. S/he will be 
required to enter the patient data needed for inclusion, which s/he will subsequently need to validate 
and sign electronically (with his/her password) in order to initiate randomization.  Following 
validation of the contents and confirmation of all the eligibility criteria on the eCRF, randomization 
is performed (by clicking a “start randomization” button) according to the characteristics determined 
by the statistician. The site subsequently immediately informs the investigator of the group to which 
the patient belongs in addition to the latter’s identifying number. The investigator's name will be 
recorded automatically and associated with the included patient no. 
 
The patients in both arms will receive instructions in order to ensure that the patients are treated 
correctly in accordance with the institutional recommendations for optimum management of their 
heart failure.   
 
The CST will be coordinated by the Clinical Research Center (CRC) of Toulouse Teaching Hospital 
Center. 

 
 
 
 
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A fax notifying of the patient name, contact details and identifier will be sent to the CST in order to 
inform them of the patients’ inclusion (regardless of the group). On the other hand, in order to inform 
the nurses at the monitoring center of a patient’s inclusion in the telemonitoring arm, they will be 
sent a fax notifying of the name and contact details, but not the patient identifier no. 
 
The equipment required for the telemonitoring group will be delivered to the patients’ homes during 
the week following the inclusion visit. 
 
The initial telephone contact by the CST (telephone visit at month 0) must take place during the days 
following the inclusion visit. 
10.4. TELEPHONE VISITS 
These visits will be conducted in the form of telephone contacts by the CST and will take place at 
0, 6, 12 and 18 months with a margin of more or less 15 days. The CST will be coordinated by the 
Clinical Research Center of Toulouse Teaching Hospital Center. 
The CST responsible for monitoring will be required to call the patient by telephone or in case of 
difficulty in contacting him/her, call a person assisting the patient and question him/her on various 
matters: 
- Medico-economic questionnaire (month 6, 12 and 18) 
- Societal acceptability questionnaire for the patients (month 0) 
- SF-36 questionnaire (at months 0, 12 and 18) (administered only to the patient) 
- Occurrence and reason for hospitalization. 
- If the patient has died, the CST must obtain information from the investigator who included 
the patient concerning the cause and date of death. S/he will thus complete the end of study 
visit page of the eCRF. 
- Occurrence of other adverse events  
- Modification of concomitant treatments 
The CST must enter the data collected in the eCRF. 
 
The last visit in the comparative period will be telephone contact by the CST at 18 months. 
 
For the patients in the standard management group only, during the last telephone contact, the CST 
must ask the patient whether s/he has scales at home and if so, whether s/he uses them at least once 
a week. 

 
 
 
 
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10.5. PREMATURE END OF STUDY VISIT 
If the patient dies or a patient in the “intensive management” group withdraws from the study 
prematurely, the CST must be kept informed in order to schedule an end of study telephone visit as 
soon as possible. Since the nurses at the monitoring center are informed earlier of this type of event 
(systematic telephone call made in case of absence of data transmission), they will be entrusted with 
informing the CST using the end of study notification sheet.  
During the last telephone contact, the CST must collect the assessment criteria from the patient or 
from the physician in case of death. 
10.6. RULES FOR TERMINATING THE RESEARCH  
The patients will be monitored until their death or until the end of the study (18 months). 
The data of the hospitalization and death events will be collected within 18 months post inclusion. 
Data collection will be continued over the extension period for the patients accepting to participate 
in the latter. 
In case of withdrawal of consent, only the events beginning between inclusion and withdrawal of 
consent will be collected. 
 
Premature withdrawal from the protocol will be performed: 
- either as a result of a deliberate decision by the patient 
- or by necessity, following a decision by the investigator in the following cases: 
o non-compliance with the study conditions  
o onset of a serious adverse event or undesirable effect 
o pregnancy 
10.7. CONSTRAINTS 
RELATED 
TO 
THE 
RESEARCH 
AND 
POSSIBLE 
COMPENSATION OF THE PATIENTS 
During the study, the patients randomized to the telemonitoring arm will be contacted every 3 weeks 
and data concerning the evolution of their disease will be collected daily.  
As part of routine monitoring, the patient consults his/her general practitioner or referring 
cardiologist whenever s/he needs to do so. 
The telecommunications process studied here does not involve any known undesirable effects. 

 
 
 
 
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We are not offering any financial compensation to patients receiving telemonitoring in one group or 
not modifying their daily life in the other.  
Patients included in OSICAT cannot simultaneously participate in another research program. There 
is no inclusion period and the patients will not be enrolled in the national file of persons engaged in 
biomedical research. 
11. MANAGEMENT OF ADVERSE EVENTS AND NEW FACTS 
11.1. DEFINITIONS  
Adverse event (Article R.1123-39 of the French Public Health Code) 
Any harmful manifestation occurring in an individual participating in biomedical research, 
regardless of whether this manifestation is related or unrelated to the research. 
 
Serious adverse event (Article R.1123-39 of the French Public Health Code and ICH E2B 
guideline) 
Any adverse event which: 
 results in death, 
 endangers the life of the individual participating in the research, 
 requires hospitalization or extension of hospitalization, 
 causes an invalidity or a significant or lasting handicap, 
 results in a congenital abnormality or malformation, 
 or any event considered medically serious 
and with regard to the medication, regardless of the dose administered. 
  
Unexpected undesirable effect (Article R.1123-39 of the French Public Health Code) 
Any undesirable effect of the product, the nature, severity or evolution of which is inconsistent with 
the information appearing in the dossiers for requesting the opinion of the CPP and for submitting a 
marketing authorization application to the competent authority. 
 
New fact (order of 24 May 2006) 
Any new item of safety data liable to result in reassessment of the benefit/risk ratio of the research, 
or which might be sufficient in order to consider modifications in the documents concerning the 
research, conduct of the research and if applicable, in use of the product. 

 
 
 
 
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11.2. DESCRIPTION OF THE EXPECTED SERIOUS ADVERSE EVENTS 
The serious adverse events related to evolution of the disease are death or hospitalization of the 
patients for a cardiovascular cause. 
No serious adverse events associated with the research are expected.  
11.3. APPROACH TO BE ADOPTED IN CASE OF AN ADVERSE EVENT OR A NEW 
FACT 
The investigator must notify the sponsor, immediately as and from the day on which s/he becomes 
aware thereof, of any serious adverse events or new facts, if occurring: 
- as and from the date of signing consent, 
- throughout the duration of patient monitoring scheduled by the research, 
- up to 30 days after the end of monitoring of the participant scheduled by the research, when 
liable to be due to the research, 
- until pregnancy reaches its term, when a pregnancy declaration is involved, 
- without any limitation of duration when the SAE is liable to be related to the experimental 
management (serious event that may occur at an interval from exposure). 
This declaration will be made using the declaration form located in the Investigator Study File  
 
Since occurrence of death or hospitalizations is the main assessment criterion, both these SAEs 
will not be declared.  
 
The study sponsor should be informed by telephone or fax within 24 working hours of 
occurrence of the serious adverse event. 
The serious adverse event declaration form, duly completed for the attention of the sponsor, should 
be filled in and forwarded within 48 working hours. 
 
Sponsor: CDM e-Health 
Medical Vice Chairman: Juan-Fernando RAMIREZ 
Address: 21, rue Albert Calmette – Building B4 – 78350 JOUY-EN-JOSAS 
Mobile: 06 35 51 11 25 
Fax: 01 39 07 61 99 
 
 
All these events must be monitored until completely resolved. Additional information 
(supplementary declaration sheet) concerning evolution of the event, if not mentioned in the initial 
report, is to be forwarded to the sponsor by the investigator. 

 
 
 
 
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Becoming pregnant during the course of or immediately following a research program does not 
constitute an SAE. A pregnancy must however be reported according to the same methods as an 
SAE, since it will undergo specific monitoring until its outcome. Any abnormality observed in the 
fetus or infant will then be reported. Any voluntary termination of pregnancy (VTP), medical 
termination of pregnancy (MTP) or miscarriage must be the subject of a pregnancy notification and 
if requiring hospitalization, must be reported according to the same methods as for an SAE.  
11.4. DECLARATION AND RECORDING OF UNEXPECTED SAES AND NEW 
FACTS  
The sponsor/vigilance unit immediately declares any unexpected SAEs and new facts occurring 
during the research: 
- 
to the National Agency for Medicines and Health Products Safety (ANSM);  
- 
to the competent Committee for the Protection of Persons (CPP). The Committee ensures, if 
necessary, that the subjects participating in the research have been informed of the 
undesirable effects and that they confirm their consent. 
 
12. STATISTICAL ASPECTS 
12.1. SAMPLE SIZE CALCULATION 
Calculation has been performed based on a type I error alpha risk of 0.05 and a power 
of 90%. We hypothesize that the intervention will help reducing the number of 
rehospitalizations and deaths (combined criterion) in the telemonitoring group versus 
the control group. We choose a bilateral hypothesis test. We have taken several 
hypotheses as a basis for this calculation: 
- 
The first starts from a frequency of the combined criterion without intervention 
of 42% and a reduction in the relative risk of 46% (according to the bases of the 
Cochrane meta analysis; taking account of a bilateral hypothesis, for a power of 
90% and an alpha risk of 5%), the number of subjects required per arm is 118, 
i.e. a total of 236 subjects. 
- 
If we formulate a lower hypothesis for the frequency of the combined criterion, 
i.e. 32% and estimate the reduction in the relative risk of occurrence of the 

 
 
 
 
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combined criterion at 30% (according to the data observed in Germany, with the 
same device, but for cohort management, with an open label, without 
randomization, still taking account of a bilateral hypothesis, for a power of 90% 
and an alpha risk of 5%), the number of subjects required per arm is 446, i.e. a 
total of 890 subjects. 
- 
The data of the French and European registers point in favor of a frequency 
of occurrence of the combined criterion of 35%, still maintaining the same 
analysis conditions, i.e. a power of 90% and an alpha risk of 5%, if the 
reduction in the relative risk is 30%, the number of subjects required per 
arm is 393, i.e. a total of 786 subjects to which we add 10% of loss to follow-
up, i.e. a scheduled overall cohort of 864 rounded up to a total of 870 subjects.  
We thus guarantee that we are not eventually faced with a problem of lack of 
power. Finally, we compared our hypothesis with the most recent bibliographical 
data in the area (Lancet 2013 Jan 5; 381(9860):29-39; Cochrane Database Syst 
Rev. 2012 Sept. 12;9.). It emerges from this analysis that our figures are similar 
to those of these research programs, backing us in the hypothesis of a total of 
870 patients.   
 
12.2. STATISTICAL METHODS USED 
 
All the study participants will be analyzed in the group to which they have been assigned (intent to 
treat analysis) in order to avoid an attrition bias. The two arms will be compared using a Student's 
test for continuous variables having a normal distribution, using a CHI2 test for discreet variables 
and using a Wilcoxon rank sum test for the categorial variables and continuous variables that are not 
normally distributed. Adherence to the intervention will be evaluated based on the number of days 
with teletransmitted weighing. The baseline demographic and clinical variable will be compared 
between the control group and telemonitoring group using descriptive statistics. It will be verified, 
despite random allocation of the patients to the two groups, whether significant differences 
concerning these variables might occur, in which case account will be taken thereof in the subsequent 
analyses relating in particular to the main objective of the study and the multivariate analyses. The 
rate of events (number of rehospitalizations or deaths) in the intervention group will be compared 
with that of the control group using Poisson regression with adjustment to an offset variable equal 

 
 
 
 
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to the duration of follow-up of each patient. Adjustments might be performed if confusion variables 
showed a significantly different distribution in the two groups. In case of overdispersion of the 
Poisson regression models, we will employ negative binomial regression (Poisson gamma 
regression). The periods of a composite variable (first hospitalization or death) will be represented 
for each of the groups using Kaplan Meier curves. These curves will be compared with each other 
using a log-rank test. We will also estimate the corresponding hazard ratios and their 95% confidence 
intervals using Cox proportional hazard models.  
Additional subgroup analyses (stratified analyses) will be performed as a function of sex, age, left 
ventricular ejection fraction, NYHA classification, telediastolic diameter value, number of patients 
recruited in each center and whether or not the patients have received therapeutic education. The 
interactions between these strata and the variable of interest will be systematically investigated. The 
number of readmissions for heart failure, the cumulative number of hospitalization days, the quality 
of life scores and the costs of treatment will also be analyzed as secondary objectives. 
It is not possible at present to perform a blind study concerning the telephone telemonitoring section. 
As matters stand, we have decided on an open-label study, as with all the studies performed with 
this type of device. We have envisaged two solutions in order to offset the bias, particularly in terms 
of information: 
- on the one hand, a per protocol analysis. This option might favor the telemonitoring arm, since one 
may believe that patients who comply with the telemonitoring will also comply with the lifestyle 
rules and the medications. Conversely, patients who comply with telemonitoring are maybe those 
who lead the least monitoring. At any rate, we will perform the analysis in intent to treat as initially 
scheduled; the per protocol analysis will be a supplementary approach. 
- on the other hand, the risk in this study is that patients may be “under-medicalized” or “over-
medicalized” in their management with regard to the recommendations of the moment apart from 
the intervention itself. Data concerning the various different aspects of management will be collected 
and analyzed subsequently in order to check for deviations from the study protocol.  
The assessment criteria are criteria of limited subjectivity: death and hospitalization. Furthermore, 
these criteria will be assessed and certified based on a dossier by an independent study committee. 
The reason or grounds for each hospitalization will be identified and validated by this committee. 
 
Study Extension period  
The patients entering the extension period will be allocated to one of the following two groups: 
- 
“Standard management / Tele-cardiology” group: patients from the “standard management” 
group of the comparative period entering the study extension period. 

 
 
 
 
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- 
“Tele-cardiology / Tele-cardiology” group: patients from the “tele-cardiology” group of the 
comparative period entering the study extension period. 
 
All the analyses relating to the patients participating in the study extension period will be presented 
by group (Standard management / Tele-cardiology vs. Tele-cardiology / Tele-cardiology) and all in 
all. 
 
The demographic variables will be presented for the patients included in the extension period. 
 
For each patient, the annualized number of hospitalizations of all causes and the annualized number 
of hospitalizations of cardiovascular origin will be calculated for the comparative period and for the 
extension period. 
The number of hospitalizations during the period of interest will be multiplied by the ratio [365 days 
/ total number of monitoring days during the period of interest]. 
These numbers will be presented descriptively. 
 
The number of deaths of all causes and the number of deaths of cardiovascular origin occurring 
during the extension period will be described. Overall survival will be represented using Kaplan 
Meier curves.  
13. MONITORING OF THE RESEARCH 
This study does not require setting up of a monitoring committee.  
14. RIGHTS OF ACCESS TO THE SOURCE DATA AND DOCUMENTS 
14.1. ACCESS TO THE DATA 
The sponsor is responsible for obtaining the consent of all the parties involved in the research in 
order to guarantee direct access to all the places where the research is conducted as well as to the 
source data, source documents and reports for the purpose of quality control and auditing by the 
sponsor. 
The investigators will make the documents and individual data that are strictly necessary for 
monitoring, quality control and audit of the biomedical research available to the persons who have 
access to these documents in accordance with the currently applicable laws and regulations (articles 

 
 
 
 
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L.1121-3 and R.5121-13 of the French Public Health Code) and in particular Regulation 2016/679 
of the European Parliament and of the Council of 27 April 2016 on the protection of individuals with 
regard to the processing of personal data and the free movement of such data (General Regulation 
on the Protection of Data - GRPD). 
The contact details of the Data Protection Officer designated by the promoter are as follows: 
Laurence Thomazeau 
Air Liquide 
Data Protection Officer 
75, Quai d’Orsay 
75007 Paris - France 
https://www.airliquide.com/fr/groupe/contactez-nous-rgpd 
14.2. SOURCE DATA 
Any document or original object allowing proof of the existence or accuracy of an element of data 
or a fact recorded during the research is defined as a source document. 
 
The originals of the laboratory assessments, the hospital reports, the death certificates, the data in 
the patient’s medical records and the scoring scales completed by the patient, the telephone call 
sheets and the eCRF will form the source data of this protocol.  
 
14.3. DATA CONFIDENTIALITY 
In accordance with the currently applicable laws (articles L.1121-3 and R.5121-13 of the French 
Public Health Code), the individuals having direct access to the source data will take all the necessary 
precautions with a view to guaranteeing the confidentiality of the data concerning the research, the 
persons engaged therein and more particularly with regard to their identity in addition to the results 
obtained. These persons, in the same manner as the investigators themselves, are bound to 
professional secrecy. 
 
The practicalities for management of the patients randomized to the telemonitoring group or 
accepting to participate in the extension period do not allow maintenance of their anonymization 
from the sponsor’s standpoint.  
Consequently, the sponsor has submitted the research to the National Commission for Data 
Processing and Freedom (CNIL). 
 

 
 
 
 
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In the database, the patients will be identified by means of a patient code. This coding will consist 
of the center number (four digits), followed by the chronological number of inclusion (four digits) 
in this center. 
 
The sponsor will ensure that each person engaged in the research has given his/her written consent 
to access to the individual data concerning him/her and strictly necessary for quality control of the 
research. 
15. QUALITY CONTROL AND ASSURANCE 
15.1. INSTRUCTIONS FOR DATA COLLECTION 
All the data specified by the protocol must be recorded on the eCRF and an explanation must be 
provided for each element of missing data. The data must be recorded as their collection progresses. 
15.2. MONITORING OF THE RESEARCH 
The setting up and monitoring of the study delegated to the service provider companies acting on 
the sponsor’s behalf. The research will be monitored by a clinical research associated (hereinafter 
known as the monitoring CRA) acting on the sponsor’s behalf. S/he will be entrusted, before the 
coordinating physician, with: 
- 
logistics and monitoring of the research, 
- 
compiling the reports concerning the latter’s state of progress, 
- 
checking updating of the case report form (request for additional information, corrections...), 
- 
communicating the SAEs to the sponsor. 
S/he will work according to the standard operating procedures, in collaboration with the clinical 
research technicians (CRT) of the Clinical Research Center (CRC) of Toulouse Teaching Hospital 
Center. 
The CRC will be responsible for coordinating the trial among the different centers and coordinating 
the work of the CRT entrusted telephone data collection. 
 
15.3. QUALITY CONTROL 
The monitoring CRA commissioned by the sponsor regularly visits each investigating center, during 
implementation of the research (in addition to 4 to 6 weeks thereafter in order to ensure that 
implementation of the study is progressing correctly in each center), several times during the 

 
 
 
 
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research according to the rate of the inclusions and at the end of the research as well as during the 
extension period. During these visits, the following elements will be reviewed: 
 informed consent, 
 compliance with the research protocol and with the procedures defined therein, 
 quality of the data collected in the case report form: accuracy, missing data, consistency between 
the data and the source documents (medical records, appointment books, originals of the 
laboratory results, etc...). 
Each visit will be the subject of a monitoring report by a written account. 
15.4. DATA MANAGEMENT 
An electronic case report form (eCRF) will be used to enter and manage the data. The software 
solution is called Smart Data Lab and will be supplied by the company BE PATIENT (located at 24 
Rue Charlot 75003 PARIS; SIRET 52958929300024, director Mr. Frédéric DURAND-SALMON). 
BePatient will also be in charge of data storage and technical maintenance of the electronic case 
report form (the company called upon by BePatient to perform data storage will be the company 
OVH).  
This electronic case report form will be accessible on line (SSL secure access) via any Internet 
navigator (Google Chrome ≥ V10, Mozilla Firefox ≥ V10, Internet Explorer ≥ V7 for PC; Safari ≥ 
V4 for Mac); it will not require installation of any additional software. Access will be performed via 
an Internet address specifically dedicated to the study (the corresponding domain name will be 
purchased after obtaining prior administrative authorizations; the sponsor will inform the CPP 
thereof as soon as the definitive address is obtained). 
The user accounts will be created by BE PATIENT, on request by the monitoring CRA. For security 
reasons, each new user will initially receive identifiers valid solely for the 1st connection; s/he will 
be asked on initial connection to change his/her password so that only s/he knows the latter. 
The data will be collected by simply keying in: 
- By the investigating physician during the inclusion visit and during the visit for inclusion in 
the extension period; 
- By the investigating physician for hospitalizations and deaths occurring during the 
comparative period and extension period; 
- By the CST of the Clinical Research Center of Toulouse Teaching Hospital Center during 
the monitoring telephone calls. 
In order to ensure traceability of the data, for each page, data recording will systematically require 
the user’s password in order to sign electronically and timestamp his/her entry. 

 
 
 
 
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Likewise, any modifications in the eCRF will systematically require the user’s password in order to 
sign electronically and timestamp his/her entry. 
The monitoring CRA will subsequently be entrusted with monitoring the data. The CRA will be able 
to send a request to the physician in case of missing or aberrant data. This request will also be 
timestamped and signed electronically and likewise the physician’s reply. 
The data are validated in accordance with the data management plan defined jointly between the 
coordinating investigator and the Methodology and Data Management Center. 
Once all the data in the case report form are considered valid by the monitoring CRA, the latter will 
lock (freeze) the page(s) in question (or the entire case report form once the latter has been fully 
completed). 
The process for freezing/thawing the data is conducted according to the procedure implemented in 
the Methodology and Data Management Center (export from the database of all the frozen data in 
CSV format, capable of subsequently being imported into SAS). 
 
All the data are backed up daily at 11 p.m. (storage organization called upon: OVH), with storage 
for 1 month on a dedicated server and the whole will subsequently be archived monthly on tape. 
 
15.5. AUDIT AND INSPECTION 
An audit may be performed at any time by persons commissioned by the sponsor and independent 
from the persons responsible for the research. Its aim is to ensure the quality of the research, validity 
of its results and compliance with the currently applicable legislation and regulations. 
 
The investigators undertake to comply with the requirements of the sponsor and the competent 
authority with regard to an audit or inspection of the research. 
 
The audit may apply to all stages of the research, ranging from development of the protocol to 
publication of the results and archiving of the data used or produced within the context of the 
research. 
16. ETHICAL AND REGULATORY CONSIDERATIONS 
The sponsor and the investigator(s) undertake to ensure that this research is conducted in compliance 
with law no. 2004-806 of 9 August 2004, as well as in accordance with Good Clinical Practices 

 
 
 
 
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(I.C.H. version 4 of 1 May 1996 and decision of 24 November 2006) in addition to the Declaration 
of Helsinki (Ethical principles applicable to medical research in human subjects, Tokyo 2004). 
 
The research is conducted according to the present protocol. Except in emergency situations 
requiring implementation of specific therapeutic procedures, the investigator(s) undertake to comply 
with the protocol in all respects, particularly with regard to obtaining of consent in addition to 
notification and monitoring of serious adverse events. 
 
This research received a favorable opinion of the Committee for the Protection of persons (CPP) of 
Limoges on 30 May 2013 and authorization by the ANSM on 11 February 2013. 
 
The sponsor of this research has taken out a civil liability insurance policy with the insurer Chubb 
Insurance Company of Europe SE (Policy no.: RC0099500300).  
 
The data recorded on the occasion of this research undergo computerized processing by service 
provider companies acting on behalf of the sponsor, in compliance with law no. 78-17 of 6 January 
1978 concerning data processing, files and freedom, amended by law 2004-801 of 6 August 2004.  
Consequently, the sponsor has submitted the research to the National Commission for Data 
Processing and Freedom (CNIL). 
 
PROTOCOL AMENDMENT  
Any substantial modification, i.e. any change liable to a have a significant impact on protection of 
persons, on the conditions of validity and results of the research, on the quality and safety of the 
products being tested, on interpretation of the scientific documents that support progress of the 
research or concerning the practicalities for conducting the latter, is subject to a written amendment 
submitted to the sponsor; the latter must obtain, prior to its implementation, a favorable opinion of 
the CPP and an authorization from the ANSM. 
 
Non-substantial modifications, i.e. those not having any significant impact on any aspect of the 
research whatsoever, are communicated to the CPP by way of information. 
 
All amendments to the protocol must be brought to the attention of all the investigators participating 
in the research. The investigators undertake to observe the contents thereof. 

 
 
 
 
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Any amendment that modifies patient management or the benefits, risks and constraints of the 
research forms the subject of a further information note or a new consent form, obtaining of which 
follows the same procedure as that mentioned above. 
 
17. STORAGE OF THE DOCUMENTS AND DATA RELATING TO THE RESEARCH 
The following documents relating to this research are archived according to Good Clinical Practices: 
- By the investigating physicians: 
- for a period of 25 years following the end of the research 
• The protocol and any amendments to the protocol 
• The case reports forms  
• The source dossiers of the participants having signed consent 
• All the other documents and correspondence relating to the research 
• The original of the signed informed consents of the participants 
All these documents are under the investigator's responsibility throughout the 
regulatory archiving period.  
 
 
- By the sponsor: 
- for a period of 25 years following the end of the research 
• The protocol and any amendments to the protocol 
• The original of the case report forms  
• All the other documents and correspondence relating to the research 
• A copy of the signed informed consents of the participants 
• The documents relating to the serious adverse events 
All these documents are under the sponsor's responsibility throughout the regulatory 
archiving period. 
 
They may not be moved or destroyed without the sponsor’s consent. At the end of the regulatory 
archiving period, the sponsor will be consulted for destruction. All the data, documents and reports 
may undergo an audit or inspection. 

 
 
 
 
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18. RULES CONCERNING PUBLICATION 
18.1. SCIENTIFIC COMMUNICATIONS 
The data provided by the investigating centers are analyzed respectively by Dr. Jean-Bernard 
Ruidavets (Epidemiology and community health laboratory of Toulouse Teaching Hospital Centre) 
and Prof. Vanina Bongard (Epidemiology service of Toulouse Teaching Hospital Centre) for the 
medical part, by Prof. Laurent Molinier (Medical Information Department of Toulouse Teaching 
Hospital Centre) for the medico-economic part and by Prof. Anne Mayère (University of Toulouse 
- UMR 5044 CNRS) for the societal part. This analysis yields a written report, which is submitted 
to the sponsor, who will communicate it to the Committee for the Protection of Persons and the 
competent authority. 
 
Any written or oral communication of the results of the research must receive the prior consent of 
the coordinating investigator and the sponsor of the research and if applicable, any committee formed 
for the research. 
 
A scientific committee will be formed. Its aim will be to validate the procedure and the publication 
plan of the articles produced based on the data of the comparative period and/or the extension period. 
It will be made up of the following members: Prof. Galinier, Prof. Pathak, Prof. Molinier, Dr 
Ruidavets, Prof. Bongard and Prof. Mayère. 
 
Publication of the main results mentions the name of the sponsor, of all the investigators who 
included or monitored patients in the research, of the methodologists, biostatisticians and data 
managers who participated in the research. Account will be taken of the international rules for 
writing and publication (Vancouver Agreement, February 2006). 
18.2. COMMUNICATION OF THE RESULTS TO THE PATIENTS 
In accordance with law no. 2002-303 of 4 March 2002, the patients are informed, on their request, 
of the overall results of the research. 
18.3. ASSIGNMENT OF DATA 
The conditions for assigning all or part of the research database are decided by the research sponsor 
and are the subject of a written contract. 
 
 

 
 
 
 
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19. INVESTIGATOR'S AGREEMENT (SIGNATURE PAGE)  
 
I have acquainted myself with the protocol entitled: 
“Optimization of the Ambulatory Monitoring for Patients With Heart Failure by Tele-cardiology - 
OSICAT” 
 
RCB ID no.: 2012-A01672-41 
 
I hereby accept the contents and the methods of conducting this study. 
 
I will do my best to perform the recruitments scheduled for the study during the inclusion period. 
 
I will provide copies of the protocol and all the data that the Sponsor has supplied me to all the 
personnel involved. I will discuss these documents with the members of this personnel in order to 
ensure that they are perfectly informed about the tele-cardiology program which is the subject of 
the study and concerning the study schedule. 
 
I hereby accept to archive the study documents (the protocol and any amendments to the protocol, 
backup of the e-CRF on a medium appropriate to data archiving, the elements of correspondence, 
original document in hard-copy form, the source dossiers of the participants having signed 
consent, the original informed consent form signed by the participants, etc.) for a period of 25 
years. 
 
 
I hereby accept to refrain from publishing all or part of the data concerning the present study, as 
stipulated by the clinical study contract signed between CDM e-Health and the investigator. 
 
 
Investigator’s name (block capitals): 
 
Date:                                                                                 Signature: 
 
 
 
 
CDM e-Health 
Name (block capitals):  
Capacity: 
 
Date:                                                                                              Signature: 
 
  
 
 

 
 
 
 
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BIBLIOGRAPHICAL REFERENCES 
1) 
Définition du Dictionnaire de Médecine Flammarion 
 
2) 
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The 
Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the 
European Society of Cardiology. Developed in collaboration with the Heart Failure 
Association (HFA) of the ESC) Eur Heart J. 2012 Aug;14(8):803-69. 
 
3) 
Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in 
a community-based population. JAMA 2004; 292: 344-50 
 
4) 
Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival 
with heart failure.. N Engl J Med 2002; 347:1397-404 
 
5) 
Najafi F, Dobson AJ, Jamrozik K. Recent changes in heart failure hospitalisations in Australia. 
Eur J Heart Fail 2007; 9:228-33 
 
6) 
Thom T, Haase N, Rosamond W et al. Heart disease and stroke statistics: a report from the 
American Heart Association Statistics Committee and Stroke Statistics Subcommittee. 
Circulation 2006; 113 (6): e85-e151 
 
7) 
Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient 
departments, and emergency departments: United States 2001-02. Vital Health Stat 2006; 13 
(159): 1-66 
 
8) 
Koelling T, Chen R, Lubwama R et al. The expanding national burden of heart failure in the 
United States: the influence of heart failure in women. Am Heart J 2004; 147: 74-8 
 
9) 
Guide des parcours de soins dans l’insuffisance cardiaque  de l’HAS, Février 2012 
 
10) 
Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart 2007; 93: 1337-46 
 
11) 
Cohen-Solal A.  Hospital management of heart failure: improvement but still room for 
improvement at discharge. Arch Cardiovasc Diseases 2008; 101: 202-3 
 
12) 
Ezekowitz JA, Bakal A, Kaul P, Westerhout CM, Amstrong PW. Acute heart failure in the 
emergency department: Short and long term outcomes of elderly patients with heart failure. 
Eur J Heart Fail 2008;10:308-14 
 
13) 
Krumholz HM, Parent EM, Tu N, et al.  Readmission after hospitalization for congestive heart 
failure among Medicare beneficiaries. Arch Intern Med 1997; 157 (1): 99-104 
 
14) 
McAlister FA, Tea KK, Taher M, et al. Insights into the contemporary epidemiology and 
outpatient management of congestive heart failure. Am Heart J 1999; 138 (1): 87-94 
 
15) 
Tsuyuki RT, McKelvie RS, Arnold JM, et al. Acute precipitants of congestive heart failure 
exacerbations. Arch Intern Med 2001; 161 (19) 2337-42 
 

 
 
 
 
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16) 
Nieminen MS, Brutsaert D, Dickstein K et al. EuroHeart Failure Survey II: a survey on 
hospitalized acute heart failure patients: description of population. Eur Heart J 2006; 27(22): 
2725-7 
 
17) 
De Groote P, Isnard R, Assyag P, Clerson P, Ducardonnet A, Galinier M, et al. Is the gap 
between guidelines and clinical practice in heart failure treatment being filled? Insights from 
the IMPACT RECO survey. Eur J Heart Fail 2007; 9: 1205-11 
 
18) 
Remme J, McMurray JV, Hobbs R, Cohen-Solal A, Lopez-Sendon J, Boccanelli A. Awareness 
and perception of heart failure among European cardiologists, internists, geriatricians, and 
primary care physicians. Eur Heart J 2008; 29: 1739-52 
 
19) 
Komajda M, Forette F, Aupetit JF, et al. Société Française de Cardiologie; Société Française 
de Gériatrie et de Gérontologie. Recommandation for the diagnosis and management of 
cardiac failure in the elderly subject. Arch Mal Coeur 2004; 97: 803-22 
 
20) 
Gislason H, Rasmussen N, Abildstrom Z, et al. Peristent use of evidence-based 
pharmacotherapy in heart failure is associated with improved outcomes. Circulation 2007; 
116: 737-44 
 
21) 
The Task Force for the diagnosis and treatment of acute and chronic heart failure 2012 of the 
European Society of Cardiology. Developed in collaboration with the Heart Failure 
Association (HFA) of the ESC. ESC Guidelines for the diagnosis and treatment of acute and 
chronic heart failure 2012. Eur Heart J 2012, doi: 10.1093/eurhearj/ehs104 
 
22) 
De Groote P, Isnard R, Assyag P, CLerson P, Ducardonnet A, Galinier M, Jondeau O, Leurs 
I, Thébaut JF, Komajda M. Is the gap between, guidelines and clinical practice in heart failure 
treatment being filled ? Insights from the IMPACT RECO survey. Eur J Heart Fail 2007; 9 
(12): 1205-11 
 
23) 
De Groote P, Isnard R, Clerson P, Jondeau O, Galinier M, Assyag P, Demil N, Ducardonnet 
A, Thébaut JF, Komajda M. Improvement in the management of chronic heart failure since 
the publication of the updates guidelines of the European Society of Cardiology. The Impact-
Reco Programme. Eur J Heart Fail 2009; 11 (1):85-91 
 
24) 
Ahmed A. Quality and outcomes of heart failure care in older adults: role of multidisciplinary 
disease-management programs. J Am Geriatr Soc 2002; 50: 1590-3 
 
25) 
Gonseth J, Guallar-Castillon P, Banegas JR, Rodriguez-Artalejo F. The effectiveness of 
disease management programmes in reducing hospital re-admission in older patients with heart 
failure: a systematic review and meta-analysis of published reports. Eur Heart J 2004; 25: 
1570-95 
 
26) 
Krumholz H, Amatruda J, Smith GL, et al. Randomized trial of an education and support 
intervention to prevent readmission of patients with heart failure. J Am Coll Cardiol 2002; 39: 
83-9 
 
27) 
Rodriguez R, Barrios A, Aznar C, Llisterri C, Moreno A, Escobar C. Clinical characteristics 
of patients diagnosed of chronic heart failure attended in primary care. Rev Clin Esp 
2007;207:337-40 

 
 
 
 
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English translation dated September 8, 2021 
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28) 
Dickstein K, Cohen-Solal A, Filippatos G, et al. The Task Force for the diagnosis and 
treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. 
Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed 
by the European Society of Intensive Care Medicine (ESICM). ESC Guidelines for the 
diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J 2008; 29: 2388-
442 
 
29) 
Roccaforte R, Demers C, Baldassarre F, Teo KK, Yusuf S. Effectiveness of comprehensive 
disease management programmes in improving clinical outcomes in heart failure patients. A 
meta-analysis. Eur J Heart Fail 2005; 7: 1133-44 
 
30) 
McAlister F, Stewart S, Ferrua S, McMurray J. Multidisciplinary strategies for the 
management of heart failure patients at high risk for a. A systematic review of randomised 
trials. J Am Coll Cardiol 2004; 44: 810-9 
 
31) 
Jaarsma T, van der Wal MH, Lesman-Leegte I, et al. Effect of moderate or intensive disease 
management program on outcome in patients with heart failure: Coordinating Study 
Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH). Arch Inter Med 
2008; 168: 316-24 
 
32) 
Heart Failure Society of America. Comprehensive heart failure practice guideline. J Card Fail 
2006; 12:10-38 
 
33) 
Capomolla S, Pinna G, La Rovere MT, et al.  Heart failure case disease management program: 
a pilot study of home telemonitoring versus usual care. Eur Heart J 2004; 6:F91-8 
 
34) 
Reigel B, Carlson B, Kopp Z, et al. Effect of a standardised nurse case management telephone 
intervention on resource use in patients with chronic heart failure. Arch Inter Med 2002; 162: 
705-12 
 
35) 
Cleland JG, Louis AA, Rigby AS, Janssen U, Balk AHMM, for the Trans-European Network-
Home-Care Management System (TEN-HMS) Study. Non-invasive home telemonitoring for 
patients with heart failure at high risk of recurrent admission and death. J Am Coll Cardiol 
2005; 45 (10): 1654-64 
 
36) 
Celler BG, Lovell NH, Basiakis J. Using information technology to improve the management 
of chronic disease. Med J Aust 2003; 179 (5): 242-6 
 
37) 
Speader J, Najjar S, Gerstenblith G, et al.  Rapid titration of carvedilol in patients with 
congestive heart failure: a randomized control trial of automated telemedicine versus frequent 
out-patient clinic visits. Am Heart J 2006; 151(4): 844.e1-10 
 
38) 
Yu CM, Wang L, Chau E, et al. Intrathoracic impedance monitoring in patients with heart 
failure: correlation with fluid status and feasibility of early warning preceding hospitalization. 
Circulation 2005; 112 (6):841-8 
 
39) 
Clark RA, Yallop JJ, Piterman L, et al. Adherence, adaptation and acceptance of elderly 
chronic heart failure patients to receiving healthcare via telephone-monitoring. Eur J Heart 
Fail 2007; 9: 1104-11 

 
 
 
 
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English translation dated September 8, 2021 
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This document is the property of Air Liquide Group                               
 
40) 
Mair F, Whitten P. Systematic review of studies of patient satisfaction with telemedicine. BMJ 
200; 320: 1517-20 
 
41) 
GESICA Investigators. Randomised trial of telephone intervention in chronic heart failure: 
DIAL trial. BMJ 2005; 331: 425 
 
42) 
DeBusk RF, Miller NH, Parker KM, et al. Care management for low-risk patients with heart 
failure: a randomized, controlled trial. Ann Intern Med 2004; 141: 606-13 
 
43) 
Goldberg LR, Piette JD, Walsh MN, et al. Randomized trial of a daily electronic home 
monitoring system in patients with advanced heart failure: the Weight Monitoring in Heart 
Failure (WHARF) trial. Am Heart J 2003; 146: 705-12 
 
44) 
Balk AH, Davidse W, Dommelen P, et al. Tele-guidance of chronic heart failure patients 
enhances knowledge about the disease. A multi-centre, randomised controlled study. Eur J 
Heart fail 2008; 10: 1136-42 
 
45) 
Braunschweig F, Ford I, Conraads V, et al. Can monitoring of intrathoracic impedance reduce 
morbidity and mortality in patients with  chronic heart failure ? Rationale and design of the 
Diagnostic Outcome Trial in Heart Failure (DOT-HF). Eur J Heart Fail 2008; 10:907-16 
 
46) 
Jaarsma T, Stromberg A, De Geest S, et al. Heart failure management programmes in Europe. 
Eur J Cardiovasc Nurs 2006; 5(3): 197-205 
 
47) 
Patel H, Shafazand M, Ekman I, Höjgard S, Swedberg K, Schaufelberger M. Home care as an 
option in worsening chronic heart failure- A pilot study to evaluate feasibility, quality adjusted 
life years and cost-effectiveness. Eur J Heart Fail 2008; 10: 675-81 
 
48) 
Stewart S, Horowitz JD. Home based intervention in congestive heart failure: long term 
implications on readmission and survival. Circulation 2002; 105 (24): 2861-6 
 
49) 
Clark RA, Inglis S, McAlister FA, Cleland JGJ, Stewart S. Telemonitoring or structured 
telephone support programs for patients with heart failure: a systematic review and meta-
analysis. BMJ 2007; 334: 442 
 
50) 
Inglis SC, Clark RA, McAlister FA, et al. Structured telephone support or telemonitoring 
programmes for patients with chronic heart failure (Review). Cochrane Database Syst Rev 
2010 Aug 4; (8): CD007228 
 
51) 
Chaudhry SI, Mattera JA, Curtis JP, et al. Telemonitoring in patients with heart failure. N Engl 
J Med 2010; 363: 2301-9 
 
52) 
Klersy C, De Silvestri A, Gabutti G, Regoli F, Auricchio A. A meta-analysis of remote 
monitoring of heart failure patients. J Am Coll Cardiol 2009; 54:1683-94 
 
53) 
Mortara A, Pinna GD, Johnson P, et al. Home telemonitoring in heart failure patients: the 
HHH study (Home or Hospital in Heart Failure). Eur J Heart Fail 2009; 11: 312-8 
 

 
 
 
 
Page 61 of 65   
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English translation dated September 8, 2021 
●●CONFIDENTIAL – RESTRICTED _Confidential Business Information 
This document is the property of Air Liquide Group                               
54) 
Dar O, Riley J, Chapman C, et al. A randomized trial of home telemonitoring in a typical 
elderly heart failure population in North West London: results of the HOME-HF study. Eur J 
Heart Fail 2009; 11: 319-25 
 
55) 
Cleland JGF, Lewinter C, Goode KM. Telemonitoring for heart failure: the only feasible 
option for good universal case ? Eur J Heart Fail 2009; 11: 227-8 
 
56) 
Desai AS, Warner Stevenson L. Connecting the circle form Home to heart failure disease 
management. N Engl J Med  2010; 363: 24: 2364-7 
 
57) 
Riley JP, Cowie MR. Telemonitoring in heart failure. Heart 2009; 95:1964-8 
 
58) 
Koehler F, Winkler S, Schieber M, et al. Telemedical Interventional Monitoring in Heart 
Failure (TIM-HF), a randomized, controlled intervention trial investigating the impact of 
telemedicine on mortality in ambulatory patients with heart failure: study design. Eur J Heart 
Fail 2010; 12: 1354-62 
 
59) 
Cohen-Solal. A, Bouhour JB, Thebaut JF. The management of patients with heart failure in 
France. Eur J Heart Fail 2000; 2:223-6 
 
60) 
Galinier M, Pathak A, Fourcade J et al. Depressed low frequency power of heart rate variability 
as an independent predictor of sudden death in chronic heart failure. Eur Heart J 2000; 21: 
475-82 
 
61) 
Pathak A, Curnier D, Fourcade J et al. QT dynamicity: a prognostic factor for sudden cardiac 
death in chronic heart failure. Eur J Heart Fail 2005; 7:26975 
 
62) 
Fonarow GC, Abraham WT, Albert NM, et al. Carvedilol use at discharge in patients 
hospitalized for heart failure is associated with improved survival: an analysis from Organized 
Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure 
(OPTIMIZE-HF). Am Heart J 2007; 153: 82 e1-11 
 
63) 
Piepoli MF, Davos C, Francis DP, Coats AJ. Exercise training meta-analysis of trials in 
patients with chronic heart failure (ExTra MATCH). BMJ 2004; 238:189 
 
64) 
Roccaforte R, Demers C, Baldassarre F, Teo KK, Yusuf S. Effectiveness of comprehensive 
disease management programmes in improving clinical outcomes in heart failure patients. A 
meta-analysis. Eur J Heart Fail 2005; 7:1133-44 
 
65) 
Cleland JG, Swedberg K, Follath F, et al. The EuroHeart Failure Survey programme – a survey 
on the quality of care among patients with heart failure in Europe. Part I: patient characteristics 
and diagnosis. Eur Heart J 2003; 24: 442-63 
 
 
66) 
Metra M, Ponikowski P, Dickstein K, et al. Advanced chronic heart failure: A position 
statement from the Study Group on Advanced Heart Failure of the Heart Failure Association 
of the European Society of Cardiology. Eur J Heart Fail 2007; 9: 684-94 
 

 
 
 
 
Page 62 of 65   
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English translation dated September 8, 2021 
●●CONFIDENTIAL – RESTRICTED _Confidential Business Information 
This document is the property of Air Liquide Group                               
67) 
De La Porte PW, Lok DJ, Van Veldhuisen DJ, et al. Added value of a physician-and-nurse-
directed heart failure clinic: results from the Deventer-Alkmaar heart failure study. Heart 2007; 
93: 819-25 
 
68) 
Berry C. Undertreatment of heart failure has high cost to patients. BMJ 2001; 322: 731 
 
69) 
Davis RC, Bathia G, Sosin M, Stubley J. Barriers to managing heart failure in primary care . 
BMJ 2003; 326: 883-7 
 
70) 
Spinewine, Swine C, Dhillon S, et al. Appropriate use of medicines in elderly in patients: 
qualitative study. BMJ 2005; 331: 935-39 
 
71) 
McHorney CA, Ware J, Raczeck AE. The MOS 36-item short form health survey (SF-36): 
Psychometric and clinical tests of validity in measuring physical and mental health constructs. 
Medical care 1993;30(3):247-263  
 
72) 
Drummond MF, Sculpher MJ, Torrance GW, O’Brien BJ, Stoddart GL. Methods for the 
economic evaluation of health care programmes. Third edition, Oxford University Press, 
Oxford 2005. 
 
73) 
Costa N,  Ferlicoq L, Derumeaux-Burel H, Rapp T,  Garnault V, Gillette-Guyonnet S, Andrieu 
S, Vellas B, Lamure M, Grand A, Molinier L. Comparison of Informal Care Time and Costs 
in Different Age-Related Dementias: A Review. BioMed Research International, 
Volume 2013 (2013), Article ID 852368, 15 pages 
 
74) 
ATIH site: http://www.atih.sante.fr/index.php?id=0008D0000000, consulted on 15/01/13 
 
75) 
ameli site: http://www.ameli.fr/accueil-de-la-ccam/index.php,consulté le 15/01/13 
 
76) 
ameli 
site: 
http://www.ameli.fr/professionnels-de-sante/transporteurs/exercer-au-
quotidien/frais-de-transport/les-situations-de-prise-en-charge.php, consulted on 15/01/2013 
 
77) 
ameli site: http://www.ameli.fr/assures/droits-et-demarches/par-situation-medicale/vous-etes-
en-arret-de-travail-pour-maladie/salarie-vos-indemnites-journalieres.php, 
consulted 
on 
15/01/2013 
 
78) 
Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from 
the SF-36. J Health Econ. 2002 Mar;21(2):271-92.). 
 
79) 
Kaufmann JC, L’entretien compréhensif, ed. Nathan Université, 2003, 
 
80) 
Bonneville L., Grosjean S., Lagacé M., Introduction aux méthodes de recherche en 
communication, éd. Gaëtant Morin, 2007  
 

 
 
 
 
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English translation dated September 8, 2021 
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This document is the property of Air Liquide Group                               
81) 
Becker H.S., Les ficelles du métier. Comment conduire sa recherche en sciences sociales, éd. 
La Découverte, 2002 
 
82) 
Beaud S., Weller F., Guide de l’enquête de terrain, éd. La Découverte, 2003  
 
83) 
WHO Europe report, published in 1996, Therapeutic Patient Education – Continuing 
Education Programmes for Health Care Providers in the field of Chronic Disease, translated 
into French in 1998. 
 
84) 
Konstam MA, Gheorghiade M, Burnett JC, et al, for the Efficacy of Vasopressin Antagonism 
in Heart Failure Outcome Study with Tolvaptan (EVEREST) Investigators. Effects of oral 
tolvaptan in patients hospitalized for worsening heart failure. JAMA 2007; 297: 1319-1331 
 

 
 
 
 
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APPENDICES 
APPENDIX 1: CORDIVA FOLDER 
 
NB: each of the sections will be presented to the patient in the form of a separate booklet, with all 
the booklets being grouped together in a folder. The pdf files of each of these booklets are enclosed 
with this document 
 
 
Summary of the CORDIVA Folder 
 
Section 1: What is heart failure and why does it occur? 
 
Section 2: Treatments for heart failure 
 
Section 3: Heart failure – interpreting the symptoms and recognizing emergency situations 
 
Section 4: Medications, one of your closest allies 
 
Section 5: Cardiac arrhythmias 
 
 
Section 6: Diet and heart failure 
 
Section 7: Psychology, stress and heart failure 
 
Section 8: Sexuality and heart failure 
 
Glossary 
 
 
 
 
 
 
 
 

 
 
 
 
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APPENDIX 2: IDENTIFICATION OF THE ALERT LEVELS 
 
The alerts are defined and triggered as indicated in the following table: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NB: what is called “RTX” in the table refers to the questionnaire box issued to the patient. 
 
NB: The RTX is the questionnaire box to which the patients reply on a daily basis. 
 
After triggering of a monitoring alert, an “intervention call” (also known as telephone intervention 
interview or telephone interview on request) is made systematically. 
The SRN calls the patient back to validate clinical genuineness of the alert and eliminate any 
artefacts (weighing while wearing a heavy garment, scales used by a third party, error in answering 
the questions, etc...). 
If the alert is genuine, the information is recorded and the patient is encouraged to consult his/her 
physician. 
An alert monitoring call is made after 24h to qualify efficiency of the alert to be recorded. An 
efficient alert is an alert resulting in management modification (treatment modification). 
So-called “technical” alerts (lack of connection, etc...) are processed conventionally by the IT 
support of the monitoring center.