Disease and Medication Knowledge Improvement: A Swiss Single-center Randomized Controlled Trial With Heart Failure Inpatients
Phase: NA
Conditions: Heart Failure With Reduced Ejection Fraction, Heart Failure; With Decompensation, Pharmacist-Patient Relations, Medication Adherence, Knowledge, Attitudes, Practice
Sponsor: University Hospital, Geneva

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Disease and Medication Knowledge Improvement: A Swiss Single-
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center Randomized Controlled Trial With Heart Failure Inpatients 
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Study type: 
 Other clinical trial according to ClinO, Chapter 4 
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6 
Risk categorization:  
risk category A  
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8 
Study registration: 
Intended for submission to the federal clinical trials database 
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(SNCTP) and the international database, clinicaltrial.gov 
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Sponsor: 
None 
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13 
Principal Investigator  
Mégane Jermini 
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Rue Gabrielle Perret Gentil 4 
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CH-1205 Geneva 
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Mégane.Jermini@hcuge.ch 
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Intervention studied: 
Educational pharmaceutical intervention for hospitalized heart 
19 
failure patients 
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Protocol identification 2022-00731 
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Version and Date: 
 
Version 2 (dated 7/22/2022) 
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PRIVACY STATEMENT 
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The information contained in this document is confidential and the property of Megane Jermini. 
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The information may not - in whole or in part - be transmitted, reproduced, published or 
29 
disclosed to any person other than the relevant ethics committee(s) and regulatory authorities 
30 
without the prior written permission of the sponsor, Pr Pascal Bonnabry, except to the extent 
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necessary to obtain the informed consent of the individuals who will participate in the study. 
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PROTOCOL SIGNATURE FORM* 
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2 
 
3 
Title 
of 
the 
study 
Disease and Medication Knowledge Improvement: A Swiss Single-center 
Randomized Controlled Trial With Heart Failure Inpatients  
Protocol 
identification 
2022-00731 
 
 
4 
 
5 
The Sponsor-Investigator has approved this version of the protocol and hereby confirms that 
6 
the study will be conducted in accordance with the protocol, the current version of the World 
7 
Medical Association Declaration of Helsinki, the ICH-GCP guidelines or ISO 14155 and 
8 
applicable local legal requirements. 
9 
 
10 
Investigator: 
11 
 
12 
Name: Ms. Mégane Jermini 
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Date: 
 _________________________ 
Signature: 
14 
 
 
15 
Department Head (Sponsor): 
16 
Pharmacy of the HUG: Pr. Pascal Bonnabry 
17 
Date: 
 _________________________ 
Signature:  
18 
Associate Physician Assistants: 
19 
Department of Internal and General Medicine: Dr. Jérôme Stirnemann 
20 
Date: 
 _________________________ 
Signature: 
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Cardiology Department: Dr. Philippe Meyer  
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Date: 
 _________________________ 
Signature:  
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*The original signed form sets at the end of this document. 
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TABLE OF CONTENTS 
1 
TABLE OF CONTENTS 
3 
2 
GLOSSARY AND ABBREVIATIONS 
4 
3 
1 SYNOPSIS OF THE STUDY 
5 
4 
2 BACKGROUND AND RATIONALE 
10 
5 
3 STUDY OBJECTIVES AND DESIGN 
13 
6 
3.1 Research hypothesis and first objective 
13 
7 
3.2 Primary and secondary endpoints 
13 
8 
3.3 Drawing of the study 
17 
9 
3.4 Study intervention 
19 
10 
4 STUDY POPULATION AND STUDY PROCEDURES 
21 
11 
4.1 Inclusion and exclusion criteria, rationale for study population 
21 
12 
4.2 Recruitment, screening and informed consent process 
22 
13 
4.3 Study Procedures 
24 
14 
4.4 Withdrawal and interruption 
37 
15 
5 STATISTICS AND METHODOLOGY 
38 
16 
5.1 
Statistical analysis plan and sample size calculation 
38 
17 
5.2 Handling of missing data and dropouts 
40 
18 
6 REGULATORY AND SAFETY ASPECTS 
40 
19 
6.1 Local regulations / Helsinki declaration 
40 
20 
6.2 Adverse events (serious) 
40 
21 
6.3 (Periodic) Safety Report 
41 
22 
6.4 Amendments 
41 
23 
6.5 (Premature) termination of the study 
42 
24 
6.6 Insurance 
42 
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7 OTHER ASPECTS 
42 
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7.1 Other ethical considerations 
42 
27 
7.2 Risk-benefit assessment 
42 
28 
8 QUALITY CONTROL AND DATA PROTECTION 
43 
29 
8.1 Quality Measurement 
43 
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8.2 Data recording and source data 
43 
31 
8.3 Confidentiality and Coding 
43 
32 
8.4 Retention and destruction of study data and biological materials 
44 
33 
9  MONITORING AND RECORDING 
44 
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10. FUNDING / PUBLICATION / DECLARATION OF INTEREST 
45 
35 
11. REFERENCES 
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GLOSSARY AND ABBREVIATION S 
1 
AE 
Adverse Event 
2 
BASEC 
Business Administration System for Ethical Committees 
3 
BMQ 
Beliefs about Medicines Questionnaire  
4 
CDMS 
ClinicalTrial Data Management System 
5 
OClinO 
Clinical Trials Ordinance 
6 
CRA 
Clinical Research Associate 
7 
CRCC  
Clinical Research Centre 
8 
CRF 
Case Report Form 
9 
CRTs 
Cardiac Resynchronization Devices  
10 
DAI 
Dimplantable automatic defibrillator 
11 
DPA 
Data Protection Act  
12 
eCRF 
Electronic Case Report Form 
13 
Educ-IC  
Therapeutic education in heart failure patients 
14 
eGFR 
Testimated glomerular filtration rate 
15 
FOPH 
Federal Office of Public Health 
16 
GCP 
Good  Clinical Practice  
17 
GPD 
Gilet portable defibrillator 
18 
HF 
heart failure 
19 
HFrEF 
Heart  failure with reduced ejection fraction 
20 
HFmrEF 
Heart  failure with mildly reduced ejection fraction 
21 
HUG 
University Hospitals of Geneva 
22 
ICH 
International  Conference on Harmonisation  
23 
LLAI 
lower limb arterial insufficiency  
24 
LRHL  
Law on Research on Human Beings  
25 
LVAD 
Left ventricular assist device  
26 
LVEF 
Left ventricular ejection fraction  
27 
MEMS 
Medication Event Monitoring System 
28 
NYHA 
New  York Heart Association 
29 
PDC 
Proportion of  days covered  
30 
PROM 
Patient Related Outcome Measure 
31 
RR 
Relative risk 
32 
SAE 
Serious Adverse Event 
33 
SARS-Cov-2 Severe acute respiratory syndrome coronavirus 2 
34 
SNCTP 
Swiss National Clinical Trials Portal 
35 
STEMI  
IST-segment elevation myocardial infarction 
36 
TPE 
Therapeutic patient education 
37 
TIA 
Transient ischemic attack 
38 
UNIGE 
University of  Geneva 
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1 
SYNOPSIS OF THE STUDY 
1 
Sponsor-
Investigator 
Megane Jermini 
University Hospitals of Geneva 
Rue Gabrielle Perret Gentil 4 
CH-1205 Geneva 
Mégane.Jermini@hcuge.ch 
Study Title 
Disease and Medication Knowledge Improvement: A Swiss Single-
center Randomized Controlled Trial With Heart Failure Inpatients  
Short title / Study ID Educ-IC  
2022-00731 
Protocol 
version 
and date 
Version 2.0 (22.07.2022) 
Study Registration  
Intended for submission to the federal clinical trials database, Swiss 
National Clinical Trials Portal (SNCTP) and the international 
database, clinicaltrial.gov 
Study category and 
Rationale 
Clinical trials with interventions that are neither a therapeutic product 
nor a transplant, category A 
Other clinical trial according to ClinO, chapter 4 
Background 
and 
Rationale  
People with heart failure are at risk of frequent hospitalization for 
cardiac decompensation. The stability of heart failure with reduced 
left ventricular ejection fraction (LVEF) is dependent on adequate 
and regular use of many medications. One reason for cardiac 
decompensation is poor medication adherence. To improve 
adherence, we would like to increase the knowledge of heart failure 
patients about their disease and their medication by conducting a 
therapeutic patient education (TPE) intervention.  
This research project consists in setting up a pharmaceutical 
intervention with an educational aim for the patient during his 
hospitalization. The intervention consists of a therapeutic education 
interview conducted by a clinical pharmacist using playful tools 
adapted to the needs of heart failure patients. This intervention will 
take place at the hospitalized patient's bed. It will be associated with 
a preparation interview for the hospital discharge and a follow-up of 
the continuity of care during the week of the return home. 
Risk/benefit 
assessment 
The educational intervention of the pharmacist does not present any 
risk for the patient because it will not impact his medical 
management. It will be given in addition to the standard basic advice 
provided to patients and will provide them with quality medical 
information on heart failure (definition, symptoms, follow-up) and its 
treatments (indications, benefits, risks). It will allow the patient to be 
autonomous in monitoring the evolution of his disease and in the 
attitudes to adopt in case of aggravation of his disease. 
Objective(s) 
The primary objective is to evaluate the change in heart failure 
patients' knowledge about their disease and medications using 
standardized inpatient teaching, accompanied by telephone follow-
up on return home. The secondary objective is to evaluate whether 
this change alters patients' beliefs about their heart failure 

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medications as well as improving their adherence to the treatments 
they receive. In the short term, this educational intervention could 
have an effect on the risk of readmission for acute heart failure at 1 
month after hospital discharge or on mortality and thus have an 
impact on healthcare system costs. 
Endpoint(s) 
Primary Endpoint:  
Patients' level of knowledge about their disease and heart failure 
medications before the educational pharmaceutical intervention and 
after the intervention, as well as at 1 month after hospital discharge. 
It will be measured by means of a 17-question questionnaire 
specifically developed for this project. This level is valued by a 
minimum score of 0 points and a maximum of 17 points. 
This criterion will also be assessed for both groups during 
hospitalization and at 1 month after discharge. 
 
Secondary endpoints :  
Beliefs about medication will be measured via the specific Beliefs 
about Medicine Questionnaire (BMQs) score before the intervention 
and at 1 month after hospital discharge. 
Adherence will be assessed with the Three Item Self Report Scale 
before the procedure and at 1 month after discharge. 
These two criteria will also be assessed in both groups, during 
hospitalization and at 1 month after discharge. 
Patient satisfaction will be assessed directly after the teaching 
intervention and at 1 month after hospitalization. 
The consumption of unplanned care such as re-hospitalizations, 
emergency medical visits will be evaluated at 1 month of 
hospitalization as well as the death rate at 1 month of hospitalization. 
A follow-up questionnaire on the return home will allow us to identify 
the patient's feelings and experiences on their return from the 
hospital 
The usability of a smartphone application, CardioMeds® , developed 
for heart failure patients by the University Hospitals of Geneva (HUG) 
will be explored at 1 month after the return home of patients who 
have agreed to install it on their smartphone and to use it. 
Their self-care skills following the use of this mobile (smartphone) 
application will also be measured using a validated questionnaire. 
Study Design 
Single-center randomized controlled trial 
 
Statistical 
considerations 
The final analysis will use an intention-to-treat analysis, including all 
patients who were randomized into the study.  
 
Continuous variables will be expressed as means ± standard 
deviations, median and interquartile range. 
  
The categorical variables will be described by their numbers and the 
proportion as a percentage.  

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Some continuous data such as age, income, left ventricular ejection 
fraction (LVEF), laboratory data, length of hospital stay, number of 
pre- and post-hospitalization medications, and number of 
hospitalizations will be reclassified into categories. Differences in 
outcomes between the intervention and control groups will be 
analyzed using the t-test for continuous variables and a Chi-square 
test for categorical variables. 
 
The main analysis assessing knowledge status will compare the 
knowledge 
score 
(dependent 
variable) 
between 
the 
two 
randomization groups (main independent variable) after adjusting for 
prior knowledge status using a linear regression or ANCOVA model.  
 
For continuous secondary outcomes (medication beliefs and 
adherence), a Student's t-test will be used to compare the mean 
values 
between 
the 
two 
groups. 
For 
binary 
outcomes 
(rehospitalization or new emergency department visit within 1 
month), a Chi-2 or Fisher exact test (if smallest expected number<5) 
will be used to compare proportions between the two randomization 
groups.  
For the satisfaction outcome, which is an ordinal qualitative variable, 
a Chi-2 or Fisher exact test (if the smallest expected number of 
participants<5) will be used. 
 
Inclusion/exclusion 
criteria 
Inclusion criteria: 
-Hospitalization in the Department of General Internal Medicine or 
Cardiology for decompensated heart failure with lowered LVEF 
(≤40%) from any cause or mildly lowered LVEF (41-49%) with the 
presence of heart failure-specific drug therapy 
-Stability of the patient's clinical condition 
- ≥ 2 heart failure medications 
- ≥18 years 
-Full capacity of discernment 
-Absence of cognitive impairment 
-Ability to speak, understand and read in French  
-Get a personal telephone (mobile or landline) 
-Consent form signed by the participant  
 
Exclusion Criteria: 
-Inability to follow study procedures 
-Institutionalized persons 
-Asylum seekers, homeless people, prisoners 
-Incapacity of judgment and discernment 
Number 
of 
participants 
with 
rationale 
The mean knowledge score found in heart failure patients 
hospitalized at the HUG and naïve to any educational program was 
7.95 points out of 17 points, with a standard deviation of 2.67. A 30% 
difference in score improvement was chosen as the smallest 

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difference to be detected with clinical significance (i.e., a score 
difference of 2.39) to be detected. Assuming a study power of 80% 
and an alpha error of 5% (two-sided), it would be necessary to recruit 
a total of 80 patients (40 per group) to be able to detect such a 
difference between the two groups. We anticipate 10% loss to follow-
up, which leads to a sample size of 90 subjects in total, or 45 per 
group. This sample size was calculated with STATA 17 (STATA 
Corporation, College Station, Texas).  
We expect to include approximately 124 patients during the 12-
month inclusion period. Indeed, 200-300 patients are hospitalized 
annually at the HUG in the Department of General Internal Medicine 
or Cardiology for heart failure with reduced LVEF, i.e., about 16-25 
patients per month. Taking into account refusals to participate and 
patients we will not have time to include, we think we can reach 62 
patients per group.   
Study Intervention  
The intervention by a clinical pharmacist includes  
- 
Targeted education on patient needs related to heart failure, 
heart failure medications and self-care; 
- 
a pre-discharge interview to consolidate key teaching 
messages and prepare the patient for their discharge 
treatment plan; 
- 
a telephone call the week of discharge to ensure 
pharmaceutical follow-up between hospital care and return 
home (continuity of care). 
Control 
Intervention 
Hospitalized heart failure patients with reduced or mildly reduced 
LVEF who do not benefit from the pharmacist's educational 
intervention but do benefit from the usual standard of care. 
Study procedures 
Each working day, the investigator will identify all patients with heart 
failure with a lowered left ventricular ejection fraction (LVEF) and 
hospitalized for cardiac decompensation at the HUG. He will assess 
whether they meet the eligibility criteria for this study. The 
investigator or a trained clinical research associate (CRA) will come 
and present the study to the eligible patients by giving them the 
information sheet and the consent form to sign if they agree to 
participate. They will be given at least 24 hours to think about 
whether they want to participate. Once the patients are included 
(eligibility criteria validated and consent signed), they will be 
randomly assigned to the intervention or control group according to 
the randomization list.  
For patients in the intervention group, the therapeutic education 
intervention will be scheduled on the same day or the next day. The 
pre-test questionnaires (knowledge, beliefs, and adherence) will be 
given to them before the educational intervention. The post-test 
questionnaires and satisfaction survey will be given to the 
participants directly after the intervention. A second discharge 
interview will be organized shortly before final discharge from the 
general internal medicine or cardiology department. A call within 7 

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days of discharge will be made and an assessment at 1 month of 
hospitalization of the primary (knowledge) and secondary (beliefs, 
adherence, satisfaction, consumption of unplanned care) endpoints 
will be made either by e-mail, postal mail, or telephone call by the 
CRA only. 
For patients in the control group, the pre-test questionnaires on 
knowledge, beliefs and adherence will be given to them on the same 
day or the day after inclusion. A post-test evaluation of knowledge, 
beliefs, adherence and rate of consumption of unplanned care will 
be performed at 1 month after hospitalization. 
Study duration and 
Schedule 
12 months 
Planned from 09/2022 for inclusion of first participant 
Planned to 09/2023 for inclusion of last participant 
Investigator(s) 
Mégane Jermini, PhD candidate, HUG Pharmacy 
Study Center 
University Hospitals of Geneva 
Rue Gabrielle Perret Gentil 4 
CH-1205 Geneva 
Data privacy 
All data collected during the study will be coded to maintain 
confidentiality of all participants. The coding key will be accessible 
only by the study investigator and recorded in a protected Excel 
document stored on a secure server at the HUG. Data will be stored 
during the study using an electronic clinical data management 
system validated by the HUG Clinical Research Center for data 
management, mySQL ver.7.x for REDCapTM to which only the 
investigator and a trained CRA will have access. Once the study is 
completed, all data collected will be archived in a secure registry of 
the University of Geneva recognized by the CRC of the HUG. 
Ethical 
consideration 
This study will show whether a therapeutic teaching intervention with 
heart failure patients carried out by a pharmacist can improve 
patients' knowledge and thus optimize their beliefs about medication, 
improve their adherence to taking them and reduce their risk of 
cardiac decompensation. This disease particularly affects an elderly 
population that is at risk of suffering from polymedication and 
cognitive disorders. Only patients without cognitive disorders will be 
included to avoid biasing the evaluation. 
This project does not present any risk for the patient because it does 
not impact the therapeutic management by the medical and nursing 
staff.  
GCP Statement 
This study will be conducted in accordance with the protocol, the 
current version of the Declaration of Helsinki, the ICH-GCP, the 
HRA, and other relevant local legal and regulatory requirements.  
 
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BACKGROUND AND RATIONALE 
1 
Heart failure is a chronic progressive disease that affects 2-4% of the Swiss population, i.e. 
2 
approximately 150,000-200,000 people. (1,2)  The mortality at 4-5 years is estimated at 50%. 
3 
(3–5). Patients hospitalized for acute heart failure, also called cardiac decompensation, have 
4 
an increased risk of mortality (6,7). A rehospitalization rate is estimated at 25% at 30 days (8–
5 
10) and 50% at 1 year (11–13). 
6 
 
7 
This disease is the leading cause of hospitalization in the elderly (2,5). According to the internal 
8 
statistics of the Department of General Internal Medicine of the University Hospitals of Geneva 
9 
(HUG), it was the first cause of hospitalization in 2019 and the 6ème cause in 2021 in a context 
10 
where the majority of patients managed in medicine suffered from COVID 19 and its 
11 
complications. According to internal hospital data obtained in 2019 with SQLape®, 7% of 
12 
patients hospitalized for cardiac decompensation were rehospitalized within 30 days of 
13 
discharge. 
14 
The main causes of rehospitalization in the heart failure patient can be multiple. They include 
15 
worsening of baseline disease, poor adherence to prescribed therapies, or lack of medication 
16 
adjustment (14–16). 
17 
 
18 
These rehospitalizations have a negative impact on patients' quality of life and their use of care 
19 
(17,18). They are also costly for the institution and for society. Indeed, it is estimated that 1-
20 
2% of healthcare expenditures are caused by patients with heart failure in both North America 
21 
and Europe, and that 2/3 of these costs are for their hospital management (19–22). According 
22 
to the hospital's cost accounting data in 2017, a hospitalization at the HUG for cardiac 
23 
decompensation was equivalent to an average cost of 21,615 CHF and 18,606 CHF in the 
24 
case of a readmission within 18 days (n =1548 patients hospitalized with cardiac 
25 
decompensation), i.e., a high cost for the institution and the healthcare system. 
26 
 
27 
Patients with heart failure must adapt their lifestyle in view of their physical abilities, which have 
28 
been severely impaired by the disease. It is therefore recommended that they follow a 
29 
restrictive therapeutic regime involving an adaptation of their lifestyle, the introduction of 
30 
numerous medications, and even the integration of medical devices (pacemaker, CRT, ICD, 
31 
LVAD, PDA) into their daily lives in order to improve their symptoms and reduce their morbidity 
32 
and mortality (23–25). 
33 
 
34 
Several studies and American and European medical societies have noted the importance of 
35 
integrating heart failure patients into multidisciplinary care and rehabilitation programs to 
36 
improve their quality of life and decrease their rate of rehospitalization (11,26,27). In Geneva, 
37 
there is a specific cardiac rehabilitation program for heart failure patients that allows them to 
38 
be informed, trained and equipped to build an environment adapted to their needs and to 
39 
ensure good adherence to their therapy. The number of patients with heart failure who benefit 
40 
from this therapeutic follow-up program is still low in Geneva today, around 30 to 40 patients 
41 
per year. A reinforcement of the offer of such programs, the implementation of a targeted 
42 
therapeutic accompaniment by means of follow-up consultations for heart failure patients or 
43 
the creation of therapeutic education programs (ETP) would be an asset for many patients. In 
44 
Switzerland, the Valais Hospital recently implemented a therapeutic education project for 
45 
patients with heart failure, including reinforced inpatient follow-up within 30 days of discharge 
46 
from hospital for cardiac decompensation (2). 
47 
 
48 
Several research teams have been able to show the positive effect of educational and/or 
49 
continuity of care support from a health care professional (5,11,28–32). Among this rich 
50 
literature, two meta-analyses are worth mentioning: Van Spall et al (5) and Son et al (33). They 
51 
showed that home nursing follow-up associated with a continuity of care or TPE intervention 
52 
on medication, self-care and self-monitoring significantly reduced readmissions of patients with 
53 
heart failure with a relative risk (RR) of 0.78 (CI 0.62-0.98) and an RR of 0.75 (CI 0.66-0.85) 
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respectively. These data corroborate other results from randomized controlled trials 
1 
demonstrating the strong impact of face-to-face educational interventions delivered by 
2 
caregivers or pharmacists on cardiac event rates, improved medication adherence, quality of 
3 
life, and risk of all-cause rehospitalization. (31,32,34,35) 
4 
 
5 
The clinical pharmacist makes a significant contribution to the education of hospitalized heart 
6 
failure patients by providing continuity of care activities to support them until a few days after 
7 
hospitalization (28,29,36–38). Meta-analyses by McKay et al (28)Viswanathan ((36) et al, 
8 
Mekonnen et al  (37)  or Ruppar et al (29) demonstrate this. Indeed, pharmacists' interventions 
9 
at discharge from hospital, including PTE, medication reconciliation or any other service aimed 
10 
at improving therapeutic adherence; 
11 
 
increase the likelihood of reducing the 30-day all-cause hospital readmission rate by 
12 
54%. (28) 
13 
 
reduced the risk of hospitalization of patients with heart failure from any cause (HR = 
14 
0.55% CI 0.39-0.77 (36), RR =0.81 (CI 0.81-0.97) (including readmissions for adverse 
15 
drug events (RR = 0.33 CI =0.20-0.53) (36,37) 
16 
 
Reduces the risk of mortality in heart failure patients (RR = 0.89 (0.81-0.99))(29) 
17 
 
18 
These positive data also include other test results that are less positive. 
19 
This is a major challenge for researchers to demonstrate the real impact of continuity of care 
20 
interventions on clinical endpoints such as rehospitalization within 30 days, emergency room 
21 
visits, and even mortality in heart failure patients. Consider two examples: 
22 
 
23 
 
the study by Garnier et al (30) study, which did not demonstrate an effect of its 
24 
enhanced continuity of care and PTE intervention on decreasing the readmission rate 
25 
or length of stay associated with readmission within 30 days of hospital discharge for 
26 
cardiac decompensation. 
27 
 
28 
 
The randomized controlled trial by Bell et al (39) which did not find that clinical 
29 
pharmacist intervention could decrease the readmission rate by 30% in hospitalized 
30 
heart failure patients despite a large sample size (n = 862). 
31 
  
32 
One of the major challenges is the need to consider ever-larger sample sizes in an attempt to 
33 
demonstrate an effect on lowering these endpoints, particularly the 30-day hospital 
34 
readmission rate. Some studies have calculated large sample sizes such as more than 600 
35 
patients to reduce the 30-day readmission rate by 8% (α = 0.05, 1-β = 80%) ((40), more than 
36 
1400 patients to detect a relative risk of 28% (α = 0.05, 1-β = 80%) (41) 
37 
 
38 
The other problem is the wide variety of evaluated continuity of care or TCE services 
39 
considered in these papers. There are no guidelines to follow as to what PTE and continuity 
40 
of care benefits should be applied or studied to demonstrate a positive effect of these types of 
41 
pharmacy activities. Bethishou et al (42) in their review concluded that no single 
42 
pharmaceutical intervention appears to be more effective than another in reducing the rate of 
43 
patient re-hospitalization. 
44 
 
45 
In this project we do not wish to consider setting up a trial to demonstrate the impact of this 
46 
new pharmacist service on a clinical judgment criterion such as the 30-day or 6-month 
47 
readmission rate because, although these seem to be the indicators of choice for evaluating 
48 
the effect of the changes on the disease, some re-hospitalizations are unavoidable due to the 
49 
presence of other factors such as co-morbidities, socio-economic factors and age, for example.  
50 
Moreover, the choice of a clinical endpoint would require the inclusion of a very large number 
51 
of patients to demonstrate their reduction, which does not seem feasible in the context of this 
52 
research project, which is part of a doctoral thesis.  
53 
Based on recently published data and wishing to be maximalist, the 30-day rehospitalization 
54 
rate in the standard population is estimated to be 15%, for an absolute difference of 3.75% 
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between the two groups to be detectable one would have to include approximately 2544 
1 
patients (α = 0.05, 1-β = 80%). This seems hardly feasible. 
2 
 
3 
Finally, the quality of evidence for the effect of heart failure disease management programs on 
4 
clinical end points is described as low to moderate according to a recent Cochrane review  (43) 
5 
which seems discouraging to researchers. 
6 
 
7 
It seems important to be able to measure the effect of transition of care interventions in heart 
8 
failure patients on other indicators of success such as Patient Related Outcome Measure 
9 
(PROM), adverse event rate, satisfaction, quality of life or medication adherence rate, for 
10 
example.   
11 
 
12 
A more recent review (44) points out the interest and even the need to answer this question 
13 
because the studies measuring it are still few. 
14 
It also highlights the importance of deploying TVE services that integrate the dimension of 
15 
continuity of care from the time of the patient's admission and not only at the time of discharge 
16 
from the hospital. The assessment of knowledge of heart failure is one of the elements to be 
17 
considered before the discharge of these patients from hospital in order to better target their 
18 
needs in terms of skills to be acquired to ensure self-care and self-monitoring to be applied at 
19 
home, and monitoring on return home. 
20 
 
21 
All these elements lead us to be particularly interested in these questions and these lines of 
22 
research.   
23 
 
24 
In the research group of hospital pharmacy of the University of Geneva of Pr Pascal Bonnabry, 
25 
we have been interested for some years in the deployment of innovative teaching methods in 
26 
the field of medication for both health professionals and patients. The creation of a reinforced 
27 
standardized therapeutic education on medication for the hospitalized patient with heart failure 
28 
and the evaluation of its impact by means of PROM seems to be a new research avenue in 
29 
the field of pharmaceutical sciences. 
30 
 
31 
In this project, it may be astute to assess a PROM such as IC patients' level of knowledge 
32 
about their disease and especially about the medications that treat it. In a second step, 
33 
measuring their beliefs associated with the medication, their adherence to the medication and 
34 
their satisfaction are other patient-related criteria that will be considered.  
35 
 
36 
Indeed, increasing patients' knowledge about their heart disease and its management would 
37 
be a key first step to improving their adherence to therapy. This would promote better treatment 
38 
effectiveness, reduce unplanned health care consumption and thus health care costs. This is 
39 
the hypothesis we are raising and to which we wish to respond through a research project. 
40 
 
41 
Currently, patients with heart failure hospitalized at the HUG do not benefit from standardized 
42 
therapeutic education on heart failure and its treatments by a health professional. The aim of 
43 
our study is to set up and evaluate this type of activity. 
44 
 
45 
The research project consists in developing a pharmaceutical service led by a clinical 
46 
pharmacist which consists of: 
47 
 
A therapeutic education interview adapted to the patient's needs on the disease of heart 
48 
failure, the medications to treat it and self-care practices at home; 
49 
 
a pre-discharge interview to reinforce the key notions acquired during the teaching and 
50 
to prepare the patient for the management of his treatments at home (new medication 
51 
plan, changes). A mobile application for smartphones (CardioMeds® )  developed at the 
52 
HUG  and containing medical information on heart failure as well as assistance in 
53 
managing medication and monitoring self-care parameters will be offered to 
54 
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 
a telephone follow-up in the days following the return home to ensure continuity of care. 
1 
 
2 
It is desirable to measure, through a clinical study, the impact of this type of care delivery to 
3 
see if it is useful and beneficial to patients. This impact will be assessed by measuring the 
4 
progression of patients' knowledge about heart failure disease and medications. A secondary 
5 
analysis will measure the impact on beliefs associated with heart failure medications and 
6 
adherence to them, and finally clinical outcomes such as readmission rates, 30-day emergency 
7 
room visits, and mortality will not be overlooked. 
8 
 
9 
The research question this project seeks to answer is: Does a targeted educational 
10 
pharmaceutical intervention for the hospitalized heart failure patient improve their knowledge 
11 
of their heart failure disease and medications?  
12 
3 
STUDY OBJECTIVES AND DESIGN 
13 
3.1 Research hypothesis and first objective 
14 
We hypothesize that the therapeutic education intervention performed by a clinical pharmacist 
15 
will improve the knowledge of patients hospitalized for heart failure decompensation with 
16 
reduced (<40%) or slightly reduced (41-49%) left ventricular ejection fraction (LVEF) in the 
17 
presence of drug therapy for heart failure. This intervention should also modify the beliefs that 
18 
some patients may have about the disease and its treatment, improve medication adherence, 
19 
and thus decrease unplanned care consumption (e.g., rehospitalizations or emergency room 
20 
visits). 
21 
 
22 
The primary objective is to evaluate the impact of a structured educational pharmaceutical 
23 
interview during hospitalization on the knowledge of the heart failure patient by conducting a 
24 
randomized controlled trial in general internal medicine and cardiology departments of a 
25 
university hospital. It will be evaluated whether there is a change in the level of knowledge 
26 
between the patients benefiting from the pharmacist's intervention and the control group that 
27 
does not benefit from it. It will also be evaluated if there is a progression in the patients' level 
28 
of knowledge after the pharmaceutical interview and if this level is maintained after 30 days of 
29 
hospital discharge (D30 post discharge). 
30 
 
31 
As a secondary objective, we will evaluate whether this educational program will influence 
32 
patients' beliefs about their medication, improve therapeutic adherence to heart failure 
33 
medication, and reduce the risk of unplanned care consumption (rehospitalization, for 
34 
example) in better educated patients. The death rate at 1 month after hospitalization will also 
35 
be evaluated. 
36 
A final secondary objective is to propose a mobile application specific to heart failure patients 
37 
called CardioMeds® and to measure its use, its usefulness and its impact on a measure of 
38 
self-care skills on a small sample of participants. 
39 
 
40 
3.2 Primary and secondary endpoints 
41 
The primary endpoint was the level of patient knowledge by setting an improvement of at least 
42 
30% (relative gain) as the smallest gain to be detected at 1 month of hospitalization in the 
43 
intervention group compared with the control group. 
44 
This value was chosen arbitrarily based on what has been found in other published research 
45 
(45–56) and also based on the experience gained from other research projects conducted at 
46 
the pharmacy in the field of education. 
47 
 
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The level of knowledge of the patients will be measured using a knowledge score that is in the 
1 
form of a knowledge assessment questionnaire created specifically for this project (Appendix 
2 
1).  
3 
 
4 
It assesses patients' knowledge on two topics: heart failure disease and heart failure 
5 
medications. It is composed of 17 questions, 8 of which are multiple-choice questions of 
6 
category K' (several correct answers), 6 of type A (only one correct answer) and 3 open-ended 
7 
questions (free text evaluated by keyword). 
8 
Six questions are related to the theme of heart failure disease and assess different elements 
9 
of knowledge such as the definition of the disease, the notion of chronicity and progression, 
10 
the symptomatology of decompensated disease, the precipitating factors of decompensation 
11 
and the correct actions to adopt in case of decompensation of the disease. The remaining 11 
12 
questions assess patients' knowledge of their heart failure medications, including the 
13 
identification of heart failure medications among all treatments, the usefulness of these 
14 
medications, the duration of treatment, the continuous adjustment of doses, the risks of non-
15 
optimal therapeutic adherence, the adverse effects of the main classes, and the correct actions 
16 
to take in the event of the occurrence of adverse effects of these medications and of forgetting 
17 
to take them. Each correct answer is worth 1 point. The scoring or quotation of the answers 
18 
will be done in the following way: 
19 
 
20 
Simple choice question with a dichotomous notation: Right answer 1 point and wrong answer 
21 
0 point 
22 
 
23 
Multiple choice question with partial credit scoring 50 (PS50): score with partial reward where: 
24 
1 if all propositions correct; 0.5 if more than 50% of propositions correct; 0 points otherwise. 
25 
 
26 
Open-ended question with partial scoring based on subjective keyword evaluation. 
27 
For example for question n° 2: 1 point if predefined keyword present; 0,5pt if partial keyword 
28 
but general concept correct; 0 pt otherwise. 
29 
 
30 
The final score can vary from 0 (no knowledge) to 17 points (excellent knowledge). 
31 
The questionnaire has never been used in an experimental context or for psychometric 
32 
analysis. There is no threshold to say that a patient has good knowledge or not. 
33 
It was developed by an internal pharmacist and an assistant pharmacist trained in TVE. It is 
34 
based on educational objectives derived from educational sessions with patients and meetings 
35 
with two patient partners from the HUG (Appendix 2). It was previously evaluated with them 
36 
and on three occasions with a group of hospitalized heart failure patients (10 patients per 
37 
version of the questionnaire). 
38 
 
39 
To determine a first basic level of knowledge of the heart failure patients hospitalized at the 
40 
HUG, the final version of the questionnaire was tested with 10 patients who had not received 
41 
any educational intervention. This analysis shows that: 
42 
 
The average baseline score is 7.95 pts out of 17.00pts (with a standard deviation of 
43 
2.67) or 46.76% of correct answers; 
44 
 
The median score of 8.25pts out of 17.00 pts (min. 4; max. 13) or 48.53% of correct 
45 
answers. 
46 
 
47 
In this clinical study, we wish to assess the level of knowledge of the intervention group before 
48 
the teaching interview, directly after the teaching interview, and at 1 month after the 
49 
participant's discharge from the hospital.  
50 
This study includes a control group in order to evaluate the real effect of the therapeutic 
51 
teaching intervention. The level of knowledge of the control group will be evaluated at inclusion 
52 
for the pre-test and at 1 month after hospitalization for the post-test. 
53 
 
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1 
Secondary endpoints included differences in medication belief and adherence scores and the 
2 
difference in the rate of unplanned care use between the two groups at 1 month post-
3 
hospitalization. 
4 
 
5 
They also focused, for the intervention group, on the difference in belief and therapeutic 
6 
adherence scores between the period before the educational intervention during 
7 
hospitalization and the period following this intervention, i.e., one month after hospital 
8 
discharge.  
9 
Four additional endpoints will be assessed after the pharmaceutical intervention with the study 
10 
population in the intervention group. 
11 
 
12 
 
Satisfaction with the pharmacist's teaching and services 
13 
 
The patient's experience and feelings upon returning home 
14 
 
The rate of re-hospitalization and emergency department visits within 30 days of 
15 
discharge. 
16 
Death rate at 1 month after hospitalization 
17 
Two parameters will be measured, from a pilot project point of view, only with the participants 
18 
of the intervention group who agreed to install and use the CardioMeds® mobile application 
19 
after hospitalization. 
20 
 
The use and usability of a specific mobile smartphone application for heart failure 
21 
patients (CardioMeds®). 
22 
 
Self-care skills learned through information delivered on the mobile app. 
23 
 
24 
 
25 
Beliefs about medicines will be assessed using the Beliefs about Medicines Questionnaire 
26 
(BMQ) developed by Horn et al. (57). This questionnaire has been validated in many chronic 
27 
diseases, including cardiac pathologies (58–61). It is composed of 18 questions that are 
28 
evaluated according to a 5-point Likert scale ranging from 1 "strongly agree" to 5 "strongly 
29 
disagree". The questionnaire is separated into 2 parts. A specific BMQ part with 10 items 
30 
measuring specific beliefs about the prescribed treatment, in terms of its necessity and worries 
31 
or concerns, and a general BMQ part with 8 other items measuring general beliefs about 
32 
medicine, including the perception of harm and overuse. This second part will not be evaluated 
33 
in this project. 
34 
The specific BMQ is composed of two 5-question subscales. It is presented in Appendix 3. 
35 
Five items assess patients' representations of their medical prescription, or more precisely, 
36 
their beliefs about the need to adhere to the prescribed drug treatment (= specific need) and 5 
37 
items measure beliefs about the risk of dependence and side effects caused by the treatments 
38 
(= specific concerns). 
39 
Scores range from 5 to 25 points for both subscales. The higher the score for specific necessity, 
40 
the more it means that the patient has a strong perception that he or she needs the medication 
41 
to be healthy and live. For specific concern, the higher the score, the more concerned the 
42 
patient is about a potential negative effect from taking the medication. A third score can be 
43 
calculated by subtracting the specific concerns from the specific needs. This gives a score of 
44 
-20 to +20. A positive value means that the need for the treatment exceeds the concerns about 
45 
taking it. This questionnaire has adequate internal consistency in a cardiac population 
46 
(Cronbach alpha = 0.76) and correlates well with other measures of beliefs (57). The validated 
47 
French version is used in this project. (62). 
48 
 
49 
Medication adherence will be assessed by means of a self-report questionnaire entitled 
50 
"Three-item self-report scale (63). This questionnaire consists of 3 questions: one that 
51 
evaluates the number of days that medication was forgotten in the last month, one that 
52 
evaluates the frequency of taking medication as prescribed by the doctor, and the third that 
53 
measures the patient's level of competence in taking medication correctly. Responses are 
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converted to a scale of 0 to 100 (0 being the lowest adherence and 100 the highest). An 
1 
average of the three responses is used to assign the adherence score. This questionnaire has 
2 
a high internal consistency (Cronbach alpha = 0.87) and correlates well with other measures 
3 
of adherence (POC and MEMS). (63–65). We translated this questionnaire into French 
4 
(Appendix 4) according to the methodology proposed by de Sousa et al. (66). 
5 
 
6 
Study participants' satisfaction will be assessed using a 13-question questionnaire (Appendix 
7 
5) after the teaching interview to evaluate the usefulness and quality of the teaching service. 
8 
A second satisfaction questionnaire consisting of 5 questions will be sent at 1 month after 
9 
hospital discharge to assess the patient's overall satisfaction with the pharmacist's care 
10 
(Appendix 6). These results will allow us to determine whether this new service should be 
11 
continued and to identify its strengths and weaknesses. 
12 
 
13 
The patient's experience and feelings upon returning home will be assessed during a 
14 
telephone call between D3 and D7 after the patient's discharge from the hospital. The objective 
15 
will be to identify the patient's needs, their feelings about going home, what they liked, what 
16 
they missed. It will also be assessed if the patient has obtained a treatment card, has organized 
17 
to go and get his medication and has organized to integrate it into his daily life. A list of 
18 
medications will be collected from the patient. The questions asked are presented in Appendix 
19 
7. 
20 
 
21 
The rate of rehospitalization or emergency room visits will be evaluated during the 
22 
telephone call made by a research assistant at D30 post hospital discharge. The cause of 
23 
hospitalization will be determined by means of the computerized hospital patient file if he is 
24 
rehospitalized at the HUG or saycte to the patient (or his attending physician depending on the 
25 
patient's cognitive functions) if he is hospitalized in another hospital. It is interesting to assess 
26 
whether the patient consumed unplanned care and whether it was related to instability of his 
27 
heart failure. This outcome was not chosen as a primary indicator because of the need to 
28 
include very large cohorts (>1000 participants) to demonstrate a statistically significant impact 
29 
as shown in the scientific literature in this area to date (5,11,30,39,67,68). 
30 
 
31 
The rate of death at 1 month after hospitalization will be assessed in both groups. This 
32 
information can be collected from the participants' computerized patient records if mentioned 
33 
or from the participants' relatives or attending physician. 
34 
 
35 
 
36 
The use and usability of the mobile smartphone application (CardioMeds® ) will be explored 
37 
by the research assistant during the telephone call at D30 post hospital discharge using a 
38 
validated standardized questionnaire (69) (Appendix 9). This tool to help with medication 
39 
administration was developed specifically for patients with heart failure and jointly by the 
40 
Cardiology Department, the Information Systems Department and the Pharmacy Department 
41 
of the HUG. It includes some of the information provided during the teaching and offers the 
42 
participant the possibility to create and use his electronic medication plan and to follow some 
43 
parameters of self-administered care such as weight and symptoms monitoring. It will be 
44 
offered to study participants by the pharmacist investigator during the pre-discharge interview. 
45 
If the patient wishes to use it for their return home, the investigating pharmacist will install the 
46 
application on the participant's smartphone/tablet and explain how to use it.  
47 
 
48 
The self-care skills of patients using CardioMeds® will be explored using a validated 
49 
questionnaire composed of 22 questions (70) (Appendix 10) to measure the effect of this 
50 
application on patients' level of empowerment in their care. 
51 
 
52 
 
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During hospitalization, the four questionnaires (knowledge, beliefs, therapeutic adherence, 
1 
and satisfaction) will be sent to the participants in paper or electronic format (on a tablet) 
2 
according to the patient's wishes by the pharmacist investigator or the research assistant. 
3 
These questionnaires will be sent again to the participants at 1 month after discharge from 
4 
hospital, as well as the two questionnaires for the participants using CardioMeds®. They will 
5 
be sent either by e-mail or by post to be completed by the patient and returned to the 
6 
investigator. In the event that these questionnaires are not returned, they will be addressed 
7 
orally during a telephone interview by a research assistant.  
8 
3.3 Study design  
9 
The design of the clinical study chosen is a parallel randomized controlled trial. This design 
10 
will allow us to evaluate the effect of our intervention without the confounding effects and 
11 
selection biases inherent in observational studies, which strengthens the internal validity of the 
12 
project.  
13 
 
14 
 
15 
The design of the study is schematized and detailed in French only in Figure 1 below.
16 

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Figure 1 : Design of the clinical study 
 

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3.4 Study intervention 
The control group will receive the usual care offered by the internal medicine service without the 
therapeutic education intervention of the pharmacist during their hospitalization. 
 
The intervention will be conducted by the pharmacist investigator with patients in the intervention 
group. These are heart failure patients with reduced LVEF, polymedicated, hospitalized for 
cardiac decompensation in the 10 general internal medicine units of the HUG. They will benefit 
from the usual medical care. The intervention will consist of an educational pharmaceutical 
interview associated with a second interview to prepare for hospital discharge (pre-discharge 
interview), followed by a telephone call a few days after hospital discharge. 
 
The therapeutic education intervention that the patient will receive will be structured in three parts: 
 
1. The first part consists of a 60-90 minute interactive edutainment session that will take 
place in the patient's bed. It will be carried out from the 3rd day of admission for a cardiac 
decompensation. The teaching is structured in two subparts, which will allow it to be 
carried out in one or two sessions if necessary to reduce its duration and preserve the 
patients' level of concentration. One or two appointments will be scheduled with the patient 
to ensure that they are available throughout the interview.  
The teaching will address 3 themes related to the disease of heart failure: the pathology, 
the drugs to treat it and the self-care and self-monitoring actions to adopt. A pedagogical 
scenario has been designed to serve as a detailed description of the teaching and as a 
teaching guide for the pharmacist trainer. It is presented in the appendix (Appendix 11). 
The teaching is standardized and can be used for all patients, regardless of their level of 
knowledge. Indeed, the elements and the games used are flexible according to the skills 
of the participants. The trainer will be able to vary his level of investment according to their 
needs, their wishes and their skills. 
Below is a brief description of the elements used in this interview: 
 
 
The pathology will be approached by means of an existing video developed by the 
Cardiology Service of the HUG explaining the definition, the mechanism of the 
disease, its effects, its complications and the causes. This video will be viewed by 
the patient after having answered the pre-test questionnaires. After viewing the 
video, a discussion with the patient, using active communication techniques (open 
questions, rephrasing,) and tools such as photolanguage, picture cards, and card 
games, will allow the patient to contextualize his or her disease, and to discuss the 
notions of chronicity of the disease, cardiac decompensation, and associated 
symptoms. 
 
 
Each of the patient's medications prescribed for heart failure during hospitalization 
will be visualized and explained (role, mechanism of action) as well as their 
benefits. A game board will be used as a teaching aid. It will allow the patient to 
associate images of his medication boxes in the different therapeutic classes. 
Real-life scenarios will be used to address the risks involved in forgetting to take 
medication. A discussion on the notion of chronicity of medication intake and the 
continuous adjustment of medication doses will be initiated. Finally, the main 
adverse effects of some therapeutic classes will be reviewed by means of a quiz 
and a discussion on the information given on the package inserts of medications. 
 
The proper daily actions that a heart failure patient should follow to assess the 
progress of his or her disease and know when to seek medical attention will be 
reviewed in subpart 1. Behaviors in case of medication-related side effects and 
forgetting to take medication will also be discussed in sub-section 2.  
 
 

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2. The second part of the intervention is characterized by a discharge interview between 
the pharmacist and the patient. It will be conducted between 1-2 days prior to discharge 
from the General Internal Medicine Service, whether the patient is going home or being 
transferred for a rehabilitation care stay. Its purpose is to prepare the patient for discharge 
from the hospital, his or her future treatment plan and self-care practices. It differs from 
the discharge interview conducted by the physician who is in charge of handing out the 
official discharge documents (discharge notice with the next medical appointments 
planned or to be organized, a prescription for medication and a treatment plan) 
 
The pharmacist will ensure that the following elements of continuity of care are 
established:  
 
the patient has a community pharmacy where he/she can collect his/her 
medication and which can follow him/her; 
 
the organization of the medication at home is adapted to the needs and lifestyle 
of the patient; 
 
Resource persons are identified when needed.  
 
 
He will give the patient a document in the form of a "memory card" that will highlight the 
important key points of the heart failure medication education. It is the patient himself, 
during this interview, who will take care to complete this document to visualize his current 
list of heart failure medications and the adverse effects to be followed.  A flyer entitled 
"control of heart failure" developed by the Cardiology Service of the HUG will be given to 
them so that they have a reference scale to rely on to evaluate their symptomatology and 
the need to consult or not and to remember the good self-care gestures to adopt at home. 
At this stage, the patient will also be asked if he/she would like to have a treatment card 
in paper format (made by the internal physician) or in digital format available on a 
smartphone (CardioMeds®). 
In case the patient wishes to benefit from this digital tool, the CardioMeds application® will 
be presented and installed by the pharmacist.  
 
3. The third step of the intervention consists of a telephone call to the patient between D3 
and D7 after discharge from hospital by the pharmacist (including patients who have 
stayed in a rehabilitation unit). This call will allow the pharmacist to ensure that the patient 
has picked up their medications and is clear on their treatment plan. It will also serve to 
ensure that the patient is not showing signs of decompensation of their heart failure. He 
or she will be available for any questions the patient may have regarding his or her health 
and will refer the patient to the appropriate resource people if necessary. 
 
The tools used to create the teaching interview and the pedagogical scenario were developed by 
a clinical pharmacist in general internal medicine, inspired by existing tools for heart failure 
patients and helped by the information needs of heart failure patients at the HUG, the opinion of 
two patient partners, and the opinion of health professionals at the HUG (clinical pharmacists, 
cardiologist, nurse). 
The scenario was validated by a group of experts composed of a clinical pharmacist specialized 
in TPE, a cardiology nurse specialized in the follow-up of heart failure patients, a cardiology 
assistant physician in charge of the heart failure and rehabilitation unit, as well as heart failure 
patients and two patient partners. The teaching was tested with three pharmacy students and two 
partner patients, one of whom had heart failure. 
 
The research project was validated by two assistant physicians: the assistant physician of the 
Department of General Internal Medicine and the cardiologist in charge of the heart failure unit of 
the HUG. 
 
 

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4 
STUDY POPULATION AND STUDY PROCEDURES 
4.1 Inclusion and exclusion criteria, rationale for study population 
 
Patients hospitalized with acute heart failure with reduced LVEF, poly-mediated from the 
Departments of General Internal Medicine and Cardiology of a Swiss university hospital in 
Geneva, will be included.   
This is a very frequently hospitalized patient population on these services. Heart failure was the 
leading cause of hospitalization in general internal medicine in 2019 and is currently in the top 10 
reasons for hospitalization despite the appearance of SARS-Cov-2 infection and its respiratory 
complications. There are other reasons why we chose this population to evaluate the impact of 
hospital-based education: 
 
o There is currently no therapeutic education offer for hospitalized heart failure patients at 
the HUG compared to other populations such as diabetic patients, patients suffering from 
chronic obstructive pulmonary disease or patients who have had a STEMI with the ELIPS 
program. 
 
o Not all patients with this pathology can be followed in the hospital by the interdisciplinary 
heart failure team of the HUG. 
 
o The evidence-based medicine guidelines written by the European Society of Cardiology 
have been updated in 2021. They will impact the drug management of heart failure 
patients. They encourage the introduction of medication in patients with reduced heart 
failure (LVEF < 40%) and also in patients with slightly reduced function (41-49%). In 
addition, the introduction of recent first-line drug therapies such as Entresto® and renal 
SGLT-2 co-transporter inhibitors (Forxiga® or Jardiance®) will result in changes in 
prescribing and the need for closer monitoring of adverse events. The reinforcement of a 
multi and interdisciplinary management is also strongly encouraged in these latest 
recommendations. Our project is in line with these recommendations. 
 
o This population is at risk for multiple cardiac decompensations and potentially avoidable 
healthcare consumption (rehospitalization, unplanned physician visits, or emergency 
room visits). 
 
o Clinical practice shows that many hospitalized patients with heart failure do not know what 
their disease is and how it is treated. A small field survey on the information needs of 
these patients was conducted with about ten patients in the General Internal Medicine 
Department of the HUG in 2021 and showed that patients were not able to define their 
heart failure disease, nor to explain the role of their medication and that they were eager 
to obtain more targeted information on their disease and their medication. 
 
 
All hospitalized patients with left heart failure with a decreased LVEF ≤40% (HFrEF) as well as 
those with LVEF between 41 and 49% (HFmrEF) only if treated with heart failure specific drug 
therapy will be approached to introduce them to the study provided they meet the inclusion criteria. 
  
The vast majority of the heart failure population is elderly and at risk for cognitive impairment. 
This may negatively influence the results of this score and bias the real impact of the educational 
intervention. To address this issue, only patients without cognitive impairment will be included. 
To identify the cognitive status of each patient, the following items will be analyzed in order of 
priority. 
- 
Judgment of the internal physician in charge of the patient. 

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- 
If the physician is in doubt about the patient's cognitive status, a Mini Mental Status (MMS) 
and a clock test (only if the MMS is greater than 24) will be performed by the investigator 
or a geriatric liaison nurse attached to the General Internal Medicine Service. Cognitive 
impairment is possible if MMS score ≤ 24 and if MMS ≥ 24 and clock test score ≤ 7. 
 
Patients hospitalized at the University Hospital of Geneva meeting the following inclusion criteria 
are eligible for the study: 
 
- 
Hospitalized in the Department of General Internal Medicine or Cardiology for 
decompensated heart failure (also called cardiac decompensation, acute heart failure)  
o with lowered left ventricular ejection fraction (LVEF) (≤40%) of any origin; 
o with slightly reduced left ventricular ejection fraction (LVEF) (41-49%) only if 
treated with the specific drug therapy for heart failure 
 
Or 
 
- 
Hospitalized in the Department of General Internal Medicine or Cardiology and presenting 
during hospitalization with decompensated heart failure (also called cardiac 
decompensation, acute heart failure)  
o With lowered left ventricular ejection fraction (LVEF) (≤40%); 
o with slightly reduced left ventricular ejection fraction (LVEF) (41-49%) only if 
treated with the specific drug therapy for heart failure 
 
- 
Stability of clinical condition as judged by the internal physician in charge of the patient 
including: 
o hospitalization in acute unit only 
o absence of oxygen dependence or oxygen dependence outside of heart failure 
o weight loss initiated if diuretic is present 
- 
≥ 2 medications to treat heart failure 
- 
≥ 18 years 
- 
Full capacity of discernment 
- 
Absence of cognitive impairment (notion of cognitive impairment in the patient record or 
judgment of the internal physician in charge of the participant or MMS ≤ 24 / MMS ≥ 24 
and clock test score ≤ 7) 
- 
Ability to speak, understand and read in French  
- 
Has a personal telephone (mobile or landline) 
- 
Signed the consent form (Appendix 8) 
 
The presence of any of the following criteria will result in the exclusion of the participant: 
- 
Inability to follow study procedures, e.g., due to a somatic medical condition such as 
confusion, language problem, psychological disorder, cognitive impairment) 
- 
Institutionalized persons (e.g., nursing home, home for the aged) 
- 
Asylum seekers, homeless people, prisoners 
- 
Person under guardianship 
- 
Short life expectancy (patient at end of life or comfort care)  
 
4.2 Recruitment, screening and informed consent process 
 
The investigating pharmacist will identify each working day (Monday to Friday) the patients 
hospitalized for cardiac decompensation in the Internal Medicine and Cardiology Departments of 
the University Hospitals of Geneva by means of the computerized patient records.  

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A computerized rule has been designed by the HUG Pharmacy to highlight the patients of the 
Services of General Internal Medicine and Cardiology presenting in their medical problems a 
cardiac decompensation.  
The pharmacist will analyze the most recent echocardiography report for each of these patients 
to determine the LVEF value of the heart. This identification step can be completed by the weekly 
lists sent by e-mail to the hospital cardiologists and to the investigating pharmacist, of the patients 
who have received a cardiac echocardiography (transthoracic and/or transoesophageal) by the 
Cardiology Department.  
 
The eligibility of patients with heart failure with diminished LVEF will be assessed by analysis of 
the computerized patient records, applying the inclusion and exclusion criteria, and by discussion 
with the internal physician in charge of the patient, particularly with regard to the capacity for 
discernment. If there is no notion of cognitive disorders in the patient's file, this will be discussed 
with the internal physician in charge of the patient to find out whether or not the patient has 
cognitive disorders. If the physician suspects it, an MMS test and possibly a clock test will be 
performed by the investigating pharmacist or by a nurse from the geriatric liaison team. If a patient 
has an MMS score of less than 24 or an MMS score of more than 24 with a clock test score of 
less than or equal to 7, he or she may have cognitive impairment and cannot be included. 
 
For all eligible patients, the investigating pharmacist will introduce them to the study on the second 
day of hospitalization. He will explain the nature of the study, its objectives, the procedures 
involved, the expected duration and the potential risks and benefits of participating. He will explain 
that the study is composed of two arms and that it is randomly determined in which group each 
participant is assigned.  
Each participant will be informed that participation is voluntary and that he/she may withdraw from 
the study at any time. Participation in or withdrawal from the study will not affect his or her 
therapeutic management. They will also be informed that their medical records will be consulted 
by the investigating pharmacist.  
All participants will receive a study information sheet and a consent form to sign in order to make 
an informed decision about whether or not to participate in the study (Appendix 8). The patient 
will be given 24 hours to decide whether or not to participate in the study. Formal consent will be 
obtained by collecting the consent form signed by the participant. It will be countersigned by the 
investigator or his representative. The consent form will be kept in the study file and a copy given 
to the participant. As soon as the patient's informed consent to participate is obtained, an 
appointment will be scheduled with the patient for the first stage of the intervention. 
Each eligible participant included in the study will be assigned an authentication number in order 
to anonymize their data and an electronic case report form (eCRF) or observation sheet will be 
created.  
 
A randomization list by random size block will be established beforehand by the HUG 
methodological support unit. This list will be held by the pharmacist in charge of the clinical trials, 
Mrs Fabiana Tirone, within the HUG pharmacy (person external to the project). Randomization 
will be automated in the Clinical Trial Data Management System CDMS RedCAPTM and activated 
for each new participant who will require the creation of a new eCRF. In case of malfunction of 
this software, Mrs. Tirone will be notified by the system and will be able to assign each participant 
to the arm according to the predefined list.  
The investigator will identify the assigned arm for each participant after collecting the patient 
consent form. The investigator will schedule the therapeutic education intervention on the same 
day for the participants in the intervention arm and collect the pre-test data from the participants. 
 
Follow-up up to 1 month post-discharge involves a potential risk of loss of participants. Some may 
withdraw from the study. These cases will be reported as, "withdrawal of informed consent" or 
"loss to follow-up". Data from patients who die during the study will be considered for final data 
analysis. 

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Participants will not be compensated for their involvement in the study. They will have the right to 
request the final results of this study. 
 
4.3 Study procedures 
Duration of inclusion: 52 weeks (June 01, 2022 to May 31, 2023)  
End of follow-up: 1-2 months (end in 08/2023) 
 
Table 1: Study Schedule 
 
 
 
 
 
 
 
 
Recruiting 
 
 
 
 
 
Evaluation at 1 month post-hospitalization 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analysis of the results 
Sept.22 
Oct.22 
Nov.22 
Dec. 22 
Jan. 23 
Feb. 23 
Tue 23 
Apr. 23 
May.23 
Jul. 23 
Jul . 23 
Aug.23 
Sept.23 
Oct. 23 
Nov .23 
Dec.23 

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Data collected 
 
Baseline patient information, medical data, heart failure data, laboratory data, vital parameter 
data, medication data will be collected for each patient included in the study once the consent 
form is completed. Other study data will be collected for pre-testing after randomization.  
The data collected for the intervention group will be collected after the teaching interview, during 
the telephone call upon discharge and for the post-test at 1 month after discharge. Data for the 
control group will be collected for the post-test at 1 month after discharge. 
 
All these data are presented in Table 2. 
 
Table 2: Patient characteristics collected 
 
Data 
Origin 
Details 
Patient information 
A * 
Name 
 
 
Medical record 
Name 
B* 
Date 
of 
birth* 
(if 
applicable) 
Medical record 
Date of birth: 
 
............./.............../............... 
 
C* 
Mailing Address* (if 
applicable) 
Medical record 
Address: 
 
 
 
 
D* 
Phone number* (if 
applicable) 
Medical 
record 
and 
patient interview 
Phone number : 
 
 
Cell phone number : 
 
 
E** 
E-mail address 
Medical 
record 
and 
patient interview 
Address: 
  
1 
Participant number 
 
 
2 
Age 
Medical record 
Age:  
 
3 
Type 
Medical record 
 Male 
 Woman 
4 
Civil status 
Medical record 
 Single 
 Married 
 Divorced 
 Widow(er) 
5 
Origin 
Medical record 
 Switzerland 
 Central Europe 
 Southern Europe 
 Southeast Europe 
 Northern Europe 
 Western Europe 
 Eastern Europe 
 Africa 
 Asia 
 Other 
6 
Ethnicity 
Patient interview 
 Caucasian 
 African 
 Asian  
 African American  

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 Other 
7 
Level of education 
Patient interview 
 Primary level (compulsory school) 
 Vocational secondary level (CFC, 
ECG) 
 Secondary II general level (Federal 
Maturité) 
 Higher vocational training I (Federal 
diploma, ES) 
 Higher Vocational Education II 
(Federal Master's Degree) 
 Universities I (Bachelor) 
(UNI/HES/EPF)  
 Universities II (Master) 
(UNI/HES/EPF) 
 Universities III (PhD) 
(UNI/HES/EPF) 
 Other 
8 
Employment 
Patient interview 
 Full-time professional activity 
 Part-time professional activity 
 Unemployed 
 Retired 
 Unemployed (house parent) 
 Unemployed (DI, social assistance) 
 Other 
9 
Annual income  
Patient interview 
 < 20'000 CHF 
 20'000-50'000 CHF 
 50'000-100'0000 CHF 
 100'000-200'000 CHF 
 > 200'000 CHF 
 I do not wish to answer 
10 
Mother tongue 
Medical 
record 
and 
patient interview 
 French 
 Swiss-German 
 Italian 
 Romanche 
 German 
 English 
 Spanish 
 Portuguese 
 Other 
11 
Level 
of 
understanding of the 
French language 
Patient interview 
 Native 
 Excellent 
 Good 
 Average 
 Low 
12 
Level of expression in 
French language 
Patient interview 
 Native 
 Excellent 
 Good 
 Average 
 Low 
13 
Assay-Curological 
Profile 
Medical 
record 
and 
patient interview 
 Basic insurance  
 Supplementary insurance 
 Private Insurance 
14 
Life context 
Medical 
record 
and 
patient interview 
 Lives alone 
 Lives with partner 
 Lives with children 
 Other 
15 
Owner of a 
smartphone or a 
tablet 
Patient interview 
 Yes 
 No 
16 
Computer owner 
Patient interview 
 Yes 

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 No 
17 
Internet connection at 
home 
Patient interview 
 Yes 
 No 
18 
Ability 
to 
use 
a 
smartphone, 
tablet, 
computer  
Patient interview 
 Basic (phone, SMS) 
 Means (e-mail, internet search 
Some basic applications) 
 Advanced (daily use, application 
installation) 
19 
Preference 
of 
the 
means 
of 
communication 
for 
contact at home 
Patient interview 
 Phone 
 E-mail 
 Mail 
 Video-conference 
20 
Frequency of e-mail 
use 
Patient interview 
 Every day 
 Several times a week 
 1 time per week 
 A few times a month 
 A few times a year 
 Never, because I don't have an e-
mail address 
 
 
Medical data 
21 
Active co-morbidities 
Medical record 
Names to be specified: 
 
 
 
 
 
22 
Cardiovascular 
history 
Medical record 
 Acute coronary syndrome 
 Angina  
 Atrial fibrillation 
 Rhythm disorders 
 Valvulopathy 
 Cardiac decompensation 
 Pericarditis 
 Myocarditis 
 Endocarditis 
 Dilated/hypertrophic/restrictive 
cardiomyopathy 
 Sarcoidosis 
 Congenital heart disease 
 Cardiogenic shock 
 Cardiorespiratory arrest 
 Cardio-renal syndrome 
 Coronary artery disease 
 Arterial insufficiency of the lower 
limbs 
 Thrombo-embolic disease 
 Cerebrovascular accident  
 Pulmonary embolism 
 Other 
23 
Cardiovascular 
risk 
factors 
Medical record 
 Hypertension 
 Diabetes  
 Dyslipidemia  
 Obesity 
 Tobacco  
 Alcohol 
 Drug  
 Family history IM 

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24 
Psychic disorders 
Medical 
record/patient 
interview/investigating 
physician 
 Absent  
 Present 
Type if present : 
 Depression 
 Anxiety 
 Bipolar Disorders 
 Other 
25 
Cognitive disorders 
Medical Record/Patient 
Testing 
 Absent 
 Present 
26 
MMS Score  
Medical Record/Patient 
Testing 
 
Number and date:  
...............   
 
(............/............./............) 
 
27 
Score Clock Test  
Medical Record/Patient 
Testing 
 
Number and date:  
 
...............   
 
(............/............./............) 
 
 
Heart Failure Data 
28 
NYHA 
classification 
of IC (at admission) 
Medical record 
 Class I 
 Class II 
 Class III 
 Class IV 
29 
FEVG  
(before admission if 
known) 
Medical record 
 
Number (%) and date: 
 
 ...............%  
 
 (............/............./............) 
 
Category: 
 HFrEF <40%. 
 HFmrEF 41-49 
 
30 
LVEF (on admission 
to hospital) 
Medical record 
 
Number (%) and date:  
 
...............%   
 
(............/............./............) 
 
Category: 
 HFrEF <40%. 
 HFmrEF 41-49 
 
31 
Cause of acute heart 
failure 
Medical 
records/Patient's 
physicians 
 High blood pressure 
 Ischemic heart disease 
 Rhythmic heart disease 
 Valvular heart disease 
 Cardiomyopathy (hypertrophic, 
dilatative, restrictive, myocarditis 
etc.) 
 Infiltrative heart disease 
(sarcoidosis, amyloidosis, 
connectivitis, hemochromatosis) 

30 
 
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 Structural heart disease 
 Medicated/Toxic 
 Endocrinopathy  
 Systemic infection 
 State of shock 
 Poor adherence to therapy 
 Hypervolemia 
 Renal insufficiency 
 Other 
32 
New 
diagnosis 
of 
heart failure 
Medical 
records/Patient's 
physicians 
 Yes 
 No 
33 
History 
of 
hospitalization 
for 
heart failure 
Medical 
records/Patient's 
physicians 
 Yes 
 No 
34 
Hospitalization 
for 
cardiac 
decompensation 
in 
the last 12 months 
Medical 
record 
and 
patient interview 
 Yes 
 No 
35 
Cardiovascular 
medical device 
Medical record 
 Pacemakers 
 Cardiac Resynchronization 
Therapy (CRT) 
 Automatic Implantable Defibrillators 
(AIDs)/ 
 Left ventricular assist (LVA) 
Laboratory data 
36 
NT-proBNP 
(admission) 
Medical record 
 
Number (ng/L) and date: ............... ng/L  
 
 (............/............./............) 
 
37 
Creatinemia  
(admission) 
 
Medical record 
Number (µmol/L) and date: 
 
 ............... µmol/L  
 
(............/............./............) 
 
38 
eGFR  
(admission) 
 
Medical record 
 
Number (mL/min/1.73 m2 ) and date: 
 
 ............... mL/min/1.73 m 2 
 
(............/............./............) 
 
Vital parameters data 
39 
Heart rate 
(admission) 
 
Medical record 
 
Number (bpm) and date: 
  
...............bpm   
 
(............/............./............) 
 
40 
Systolic 
blood 
pressure  
(admission) 
 
Medical record 
 
Number (mmHg) and date: 
 
...............mmHg   
 
(............/............./............) 

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41 
Diastolic 
blood 
pressure 
(admission) 
 
Medical record 
 
Number (mmHg) and date:  
 
...............mmHg   
 
(............/............./............) 
 
42 
Weight  
(admitted) 
Medical record 
 
Number (kg) and date : 
  
...............kg   
 
(............/............./............) 
 
43 
Weight  
(exit) 
Medical record 
 
Number (kg) and date :  
 
...............kg   
 
(............/............./............) 
 
44 
Body 
mass 
index 
(Kg/m2 ) 
Medical record 
 <18 
 18-24.9 
 25-29.9 
 30-34.9 
 35-39.9 
 ≥40 
  
Drug Data 
45 
Medication at home 
before admission 
Medical record 
Date: (............/............./............) 
 
Specialty / INN / Dosage / Dosage 
e.g. Forxiga, dapagliflozin, 10mg, i.d 
 
 
 
 
 
 
 
 
 
 
 
 
 
46 
Number 
of 
medications 
before 
hospitalization 
Medical 
record/patient 
interview/ 
 
 0  
 1-2 
 3-4 
 >4 
47 
Number 
of 
heart 
failure 
medications 
prior 
to 
hospitalization 
Medical 
record/patient 
interview/ 
 0  
 1 
 2 
 3 
 4 
 5 
 >5 

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48 
Heart 
failure 
medication 
list 
(home) 
Medical record 
 Diuretic  
 Beta-blocker  
 IECA/ARA 
 ARNI 
 Aldosterone antagonist (ARM) 
 SGLT2 inhibitor 
 Ivabradine 
 Digoxin 
 Vericiguat 
 
49 
Heart 
failure 
medication 
list 
(hospitalization) 
Medical record 
 Diuretic  
 Beta-blocker  
 IECA/ARA 
 ARNI 
 Aldosterone antagonist (ARM) 
 SGLT2 inhibitor 
 Ivabradine 
 Digoxin 
 Vericiguat 
50 
Heart 
failure 
medication 
list 
(hospital discharge) 
Medical record 
 Diuretic  
 Beta-blocker  
 IECA/ARA 
 ARNI 
 Aldosterone antagonist (ARM) 
 SGLT2 inhibitor 
 Ivabradine 
 Digoxin 
 Vericiguat 
51 
Medication 
management in the 
home 
Patient interview 
 Autonomous 
 Nursing care 
 Pharmacy 
 Caregivers 
52 
Medication 
management tool 
Patient interview 
 Paper Medication Plan 
 Electronic Medication Plan 
 Weekly/Plus 
 Daily unit dose sachet  
 Unit discount by the pharmacy 
 Other 
53 
Frequency of visits to 
your 
regular 
pharmacy 
Patient interview 
 Several times a week 
 1 time per week 
 2-3 times a month 
 1 time per month 
 1 time every 2-3 months 
 2 times a year 
 1 time per year 
 Never 
54 
Quality 
of 
the 
relationship with your 
city pharmacist 
Patient interview 
 No particular relationship 
 Wrong  
 Neither good nor bad 
 Good  
 Very good 
Pre-test data 
55 
Knowledge 
Questionnaire 
Patient interview 
Answer for each question (detailed 
in the documents specific to the 
questionnaires) 
56 
Score 
Calculation 
Value: 
 
57 
Belief questionnaires 
Patient interview 
Answer for each question (detailed in 
the documents specific to the 
questionnaires) 

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58 
Need score 
Calculation 
Value: 
 
59 
Concern score 
Calculation 
Value: 
 
60 
Differential score 
Calculation 
Value: 
 
61 
Membership 
questionnaire 
Patient interview 
Answer for each question (detailed in 
the documents specific to the 
questionnaires) 
62 
Membership score 
Calculation 
Value: 
 
Post-interview FTE data 
 (for intervention group only) 
63 
Knowledge 
Questionnaire 
Patient interview 
Answer for each question (detailed 
in the documents specific to the 
questionnaires) 
64 
Score 
Calculation 
Value: 
 
65 
Satisfaction 
questionnaire 
Patient interview 
Answer for each question (detailed in the 
documents specific to the questionnaires) 
Output data (3-7 days) 
(for intervention group only) 
66 
Length of stay in 
acute care hospitals 
Medical record 
 
Number of days : 
 
Category: 
 0-3 days,  
 3-7 days 
 7-10 days 
 10-14 days 
 14 -30 days 
 > 30 days 
67 
Place of transfer at 
the 
end 
of 
the 
hospitalization 
Medical record 
 Home 
 Rehabilitation Service 
 Other acute care unit 
 Other acute care service 
 Other hospital 
68 
Follow-up 
by 
a 
cardiologist 
Patient interview 
 Yes 
 No 
69 
Date of cardiologist's 
visit 
Patient interview 
date:  
 
(............/............./............) 
 
70 
Weight at home 
Patient interview 
Number (kg) and date :  
 
...............kg   
 
(............/............./............) 
 
71 
Increase in weight 
Patient interview 
 Yes 
 No 
 
If yes, number of kilograms : 
 
72 
Symptoms of heart 
failure 
Patient interview 
 
Water accumulation in the ankles, 
legs, abdomen or lungs 
 
Shortness of breath when making 
an effort 
 
Difficulty breathing, sometimes with 
a dry cough 

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 
The sensation of suffocation in the 
supine position 
 
Rapid weight gain (>2kg in 3 days) 
 
Fatigue 
 
Dizziness 
 
Palpitations 
 
Chest pain 
 
73 
Pharmacy visited 
Patient interview 
Name: 
 
Date: ........../............/........... 
 
Number 
of 
days 
after 
hospitalization: .................. 
 
74 
Obtaining medication 
Patient interview 
 
Yes 
 
No 
If so, what type? 
 
Delayed delivery time of 1-
2 
days 
because 
your 
pharmacy had to order 
certain medications. 
 
Delayed delivery time of 
more 
than 
1 
week 
because your pharmacy 
had 
to 
order 
certain 
medications. 
 
Delayed time to obtain and 
date 
of 
obtaining 
still 
undetermined 
 
Inability to get to the 
pharmacy on your own 
 
You forgot to pick them up 
 
Other (please specify): 
.........................................
.........................................
...... 
 
75 
Heart 
failure 
medication list 
Patient interview 
Date: (............/............./............) 
 
Specialty / INN / Dosage / Dosage 
e.g. Forxiga, dapagliflozin, 10mg, i.d 
 
 
 
 
 
 
76 
Adverse 
drug 
reactions 
Patient interview 
 Extreme fatigue 
 Dizziness when you stand 
up 
 Vision problems 
 Headaches 
 A frequent need to urinate 
 Low 
blood 
pressure 
(<110mmHg) 
 A low heart rate (<60 bpm) 
 Rapid weight gain (>2kg in 
3 days) 

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 Worsening of shortness of 
breath or edema 
 Dry cough 
 Dry mouth and intense 
thirst 
 Dry skin 
77 
Physical and moral 
feelings of the patient 
on returning home 
Patient interview 
Free response  
 
78 
Experience 
and 
feeling of going home 
Patient interview 
Free response  
 
 
 
 
Post-test data at 1 month 
79 
Knowledge 
Questionnaire 
Patient interview 
Answer for each question (detailed in the 
documents specific to the questionnaires) 
80 
Score 
Calculation 
Value: 
 
81 
Belief questionnaires 
Patient interview 
Answer for each question (detailed in the 
documents specific to the questionnaires) 
82 
Score  
need 
Calculation 
Value: 
 
83 
Concern score 
Calculation 
Value: 
 
84 
Differential score 
Calculation 
Value: 
 
85 
Membership 
questionnaire 
Patient interview 
Answer for each question (detailed in the 
documents specific to the questionnaires) 
86 
Score 
Calculation 
Value: 
 
87 
Satisfaction 
questionnaire 
Patient interview 
Answer for each question (detailed in the 
documents specific to the questionnaires) 
88 
CardioMeds Usability 
Questionnaire 
Patient interview 
Answer for each question (detailed in the 
documents specific to the questionnaires) 
89 
CardioMeds 
Self-
Care Questionnaire 
Patient interview 
Answer for each question (detailed in the 
documents specific to the questionnaires) 
90 
Heart 
failure 
medication list 
Patient interview  
Date: (............/............./............) 
 
Specialty / INN / Dosage / Dosage 
e.g. Forxiga, dapagliflozin, 10mg, i.d 
 
 
 
 
 
 
91 
Re-hospitalization 
1 
month 
after 
hospitalization 
Patient interview 
 Yes 
 No 
92 
Emergency 
visits 
(Hospital/Ambulatory
) 
1 
month 
after 
hospitalization 
Patient interview 
 Yes 
 No 
93 
Deaths  
1 
month 
after 
hospitalization 
Medical 
records, 
relatives, 
attending 
physician 
 Yes 
 No 

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*This participant identification data will not appear in the participant's Case Report Form (CRF). 
It will be collected by the investigator and stored separately from the CRF in a secure electronic 
file accessible only by the investigator and the CRA. 
** The e-mail address will be visible in the eCRF but only consultable by the investigator and the 
clinical research associate. It must appear in the CDMS (RedCapTM ) to allow the setting of the 
sending of the questionnaires at 1 month for the participants having wished to receive them by e-
mail. As soon as all the participant's data have been collected and the study is closed, the e-mail 
addresses will be deleted from the CDMS. 
 
For any data that is not complete during hospitalization, it will be obtained by phone call upon the 
participant's return home. 
 
Assessment of the level of knowledge (primary outcome): 
 
The level of knowledge of the patients will be assessed in the intervention group by a 
questionnaire (Appendix 1) on three occasions: at time 0 before any intervention as a pre-test, 
after the teaching interview as post-test n°1 and finally at 1 month post-discharge as post-test 
n°2.  
 
This questionnaire will be proposed in the control group at time 0 (pre-test) and at 1 month after 
hospitalization (post-test). 
 
During hospitalization, the questionnaire will be sent to the patient by the investigating pharmacist 
and will be completed by the patient himself with the help of the pharmacist if necessary.  
At 1 month after discharge, the questionnaire will be sent to the patient by email or post. If no 
return is obtained, the research assistant will address the questionnaires to them during a phone 
call. 
 
Assessment of beliefs about medications (secondary outcome) 
 
Beliefs about medicines will be assessed indirectly using the Beliefs about Medicines 
Questionnaire (Appendix 3) at time 0 (pre-test) after obtaining the consent form and at 1 month 
after hospitalization (post-test) in both groups.  
During hospitalization, the questionnaire will be sent to the patient by the investigating pharmacist 
and it will be filled in by the patient himself with the help of the pharmacist if necessary. One 
month after discharge, the questionnaire will be sent to the patient by email or post. If no return 
is obtained, the research assistant will send them the questionnaires during a telephone call. 
 
Assessment of therapeutic adherence (secondary outcome) 
 
Adherence to therapy will be assessed for all participants with the 3-item self-report questionnaire 
(Appendix 4) on two occasions. It will be presented to the participant by the investigator at time 0 
after obtaining the consent form (pre-test), as well as at 1 month post-hospitalization. During 
hospitalization, the questionnaire will be sent to the patient by the investigating pharmacist and 
completed by the patient himself with the help of the pharmacist if necessary. 
At 1 month after discharge, the questionnaire will be sent to the patient by email or post. If no 
return is obtained, the research assistant will address the questionnaires to them during a phone 
call.  
 
 
Rate of rehospitalization and emergency room visits (secondary outcome) 
 

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All study participants will be asked during the 1-month postdischarge telephone call whether they 
have been readmitted to the hospital since discharge and for what reason, whether they have 
been seen in the hospital or by their physician for signs of cardiac decompensation.  
 
Death rate (secondary outcome) 
 
In case of non-response of participants to the post-test questionnaires, it will be investigated by 
means of the computerized patient record of the hospital or with the relatives or the attending 
physicians in charge of the participants if the participants died within one month of the hospital 
discharge. 
 
 
Assessment of satisfaction (secondary outcome) 
 
Satisfaction with the teaching interview will be assessed by means of a questionnaire that the 
patient will complete directly after the teaching interview (Appendix 5). 
Overall satisfaction with the pharmacist's care will be assessed at 1 month post discharge. They 
will be evaluated only in the intervention group 
The questionnaire will be sent to the patient by email or regular mail. If no return is obtained, the 
research assistant will address the questionnaires to them during a telephone call (Appendix 6). 
 
 
Evaluation of the patient's experience and feelings upon return home (secondary outcome) 
 
The patient's experience and feelings on returning home will be evaluated for the intervention 
group during a telephone call between D3 and D7 of the hospital discharge by the investigating 
pharmacist using a questionnaire sent by the investigating pharmacist (Appendix 7) 
 
 
Use of the electronic treatment plan (secondary outcome) 
 
Patients who were presented with and installed the CardioMeds mobile application® during 
hospitalization will be asked if they used it and if they were satisfied with it. It will be the research 
assistant who will collect these elements during the telephone call at 1 month post hospital 
discharge using a validated standardized questionnaire (Appendix 9). In addition, as the mobile 
application is specifically designed to empower the patient in his care, a validated standardized 
self-care questionnaire will also be filled out on this occasion (Appendix 10). 
 
 
Other item evaluated 
 
The participant will be asked during the 1-month telephone call if he/she has entered a specific 
cardiac rehabilitation program for heart failure. He/she will also be asked to provide his/her last 
medication list to analyze if there have been any changes in the treatment of heart failure since 
discharge. 
4.4 Withdrawal and interruption 
A participant may withdraw from the study at any time if he or she no longer wishes to participate. 
A participant will be withdrawn from the study if he/she dies, if his/her health condition deteriorates 
to the point where he/she can no longer meet the inclusion criteria or be physically able to follow 
the pharmacist's intervention, if he/she loses his/her capacity of discernment, if he/she cannot be 
reached by telephone after discharge from the hospital.  
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withdrawal of informed consent. Therefore, we choose to implement an intention-to-treat analysis. 
The data collected will be retained until the loss of a participant. The number of lost to follow-up 
will be specified in the results in the form of a flowchart. All data used in the analysis will be 
anonymized afterwards. 
5 
STATISTICS AND METHODOLOGY 
This chapter of the protocol describes the research hypotheses, statistical analysis plan, sample 
size, and treatment of missing data.  
It was submitted to Pr Gayet-Agéron, head of the methodological support unit of the HUG 
clinical research center, who assisted us in the construction of these elements and their 
validation. 
 
The final analysis will be based on the intention-to-treat principle, i.e. including all patients who 
were randomized in the study.  
 
For the basic data, continuous variables will be described as means and standard deviation, 
median and inter-quartile range.  
 
The discrete or categorical variables will be described by their numbers and relative proportion, 
or even the mean and standard deviation, depending on the variables  
 
Some continuous data such as age, left ventricular ejection fraction (LVEF), laboratory data, 
length of hospital stay, number of pre- and post-hospitalization medications will be reclassified 
into categories and presented as numbers and relative proportion of each category. Differences 
in outcomes between the intervention and control groups will be analyzed using the t-test for 
continuous variables and a Chi-Square test for categorical variables. 
 
The main analysis assessing knowledge status will compare the knowledge score (dependent 
variable) between the two randomization groups (main independent variable) after adjusting for 
knowledge status at baseline using a linear regression model or ANCOVA.  
 
For continuous secondary outcomes (medication beliefs and medication adherence), a Student's 
t test will also be used to compare mean values between the two groups. For binary outcomes 
(re-hospitalization or new emergency department visit within 1 month), a chi-2 test (or Fisher 
exact test if the smallest expected number of patients is <5) will be used.  
For the satisfaction outcome, which is an ordinal qualitative variable, a Chi-2 test (or Fisher's 
exact test if the smallest expected number of participants is <5) will be used. 
5.1 Statistical analysis plan and sample size calculation 
 
Research Hypotheses 
The hypothesis of this project is that patients with heart failure who have received an educational 
interview combined with follow-up by the hospital pharmacist show an increase in their knowledge 
score after the intervention compared with the control group at 1 month after hospital discharge. 
The null hypothesis is that there is no improvement in the knowledge score at 1 month after 
hospital discharge. 
This hypothesis leads us to evaluate the primary endpoint: the improvement of knowledge about 
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cardiac decompensation.  
 
Sample size 
To test our hypothesis, we need to define an adequate sample size. 
To do this, we initially consulted the literature. Several studies have demonstrated an 
improvement in patient knowledge after pharmacist intervention with approximately 100-200 
patients (45–56). 
The questionnaire used to measure patient knowledge has never been studied to date. We tested 
it in 10 hospitalized heart failure patients who were naïve to any teaching intervention.  
This analysis shows that: 
 
The average baseline score is 7.95 pts out of 17.00pts (with a standard deviation of 2.67), 
i.e. 46.7% of correct answers; 
 
The median score of 8.25pts out of 17.00 pts (min. 4; max. 13) is 48.5% correct answers. 
By setting a relative gain of 30% as the smallest difference to be detected, this would be 
equivalent to showing an improvement in the mean score of at least 2.39 points (±7.01) (i.e., a 
mean score increase from 7.95 to 10.34pts). 
Assuming a two-sided alpha of 5% and a power of 80%, 40 subjects per group should be included, 
for a total of 80 subjects.  Considering a loss to follow-up in about 10% of the study subjects, the 
required sample size would be at least 90 subjects (45 subjects per group). This sample size was 
calculated with STATA 17 (STATA Corporation, College Station, Texas). 
We also need to consider the average number of patients hospitalized at the HUG for left heart 
decompensation with decreased LVEF to define the inclusion time and feasibility of this project. 
Note that according to internal hospital statistics, the number of patients hospitalized in general 
internal medicine for left heart decompensation (all severities and LVEFs combined) in 2019 was 
641 and 434 between January and November 2021. It is considered that 50% of these patients 
have a reduced LVEF, equivalent to 200-330 patients per year who could benefit from our 
intervention or approximately 16-25 patients per month. A certain number of these patients will 
not meet the inclusion criteria and a small number, approximately 30%, will agree to participate, 
as shown by certain studies in heart failure patients (71–74). In addition, some patients will be 
missed by the investigator who will only work part-time on this project.  
Based on all these elements, we expect to include approximately 124 patients (62 per group) over 
12 months, to show a progression of knowledge which is a sufficient number to guarantee the 
statistical power of the study. 
 
Planned analyses  
 
Primary analysis 
 
To answer the main research question, a linear regression (or ANCOVA) will be performed to 
compare the estimated mean scores at 1 month between the two randomization groups after 
adjustment for the baseline knowledge score. For subjects for whom the knowledge score could 
not be obtained at post-test, we will use the baseline value as post-test value in order to avoid 
missing data. The threshold of statistical significance under the null hypothesis is set with a type 
I error, α < 0.05 
The primary analysis will be carried out by a statistician from the Methodological Support Unit of 
the HUG Clinical Research Centre, who will be commissioned by the investigator once the data 
of the last patient included have been collected.  
 
 
 

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Secondary analyses 
 
Comparisons of continuous secondary outcomes between the two randomization groups will be 
made by Student's t tests; comparisons of categorical or ordinal qualitative secondary outcomes 
will be made using a Chi-2 test or Fisher's exact test (in case of smaller expected number <5).  
The analyses will be carried out by a statistician from the methodological support unit of the HUG 
clinical research center on a specific and recognized computer software. 
 
Deviation(s) from the original statistical plan 
 
Any deviation from the original statistical plan will be noted and explained in the final report. 
 
5.2 Handling missing data and dropouts 
The status of a longitudinal study is related to a high degree of loss to follow-up. In subjects for 
whom the knowledge score could not be obtained at post-test, we will use the baseline value as 
the post-test value in order to avoid missing data.  
6 
REGULATORY AND SAFETY ASPECTS 
6.1 Local regulations / Helsinki declaration 
This study is conducted in accordance with the protocol, the current version of the Declaration of 
Helsinki, the ICH-GCP. If the clinical trial is not conducted in accordance with the ICH-GCP, the 
above paragraph must be adapted accordingly (ClinO Art. 5, Abs 2), to the HRA as well as to 
other locally relevant legal and regulatory requirements. 
 
6.2 Adverse events (serious) 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study subject 
that is not necessarily causally related to the trial procedure. Thus, it can be any adverse or 
unintended finding, symptom, or illness associated over time with a trial procedure, whether or 
not it is related to the trial procedure. 
A serious adverse event (SAE) (ClinO, s. 63) is any untoward medical event that 
- results in death or is life threatening, 
- requires hospitalization or extension of an existing hospitalization, 
- results in a persistent or significant disability or impairment, or 
- causes a birth defect or congenital malformation.  
 
The investigator and sponsor assess the causality of the event to the trial intervention (see table 
below based on terms given in the ICH E2A guidelines). 
 
Any event assessed as possibly, probably, or definitely related is classified as related to the trial 
intervention (Table 3) 
 
Table 3: Description of Adverse Drug Event Types 
Relationship 
Description 

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Some 
Temporal relationship 
Improvement after stopping treatment*. 
Recurrence after resumption of treatment 
(or other evidence of the presence of the drug) 
Probable  
Temporal relationship 
Improvement after stopping treatment*. 
No other obvious cause 
Possible 
Temporal relationship 
No other obvious cause 
Improbable 
Any evaluable reaction that does not meet the above conditions. 
Not related 
A causal relationship can be excluded. 
* Improvement after the "unchallenge" is only taken into account if it applies to the reaction 
 
The investigator and sponsor rate the severity of the event as mild, moderate or severe. Mild 
means the complication is tolerable, moderate means it interferes with daily activities, and severe 
means it makes daily activities impossible. 
Reporting of SAEs (see ClinO, Art. 63) 
 
All AEs are documented and reported immediately (within 24 hours) to the study sponsor. 
If it cannot be excluded that the SAE in Switzerland is attributable to the intervention under study, 
the investigator reports it to the Ethics Committee via BASEC within 15 days. 
 
Monitoring of serious adverse events  
 
Any patient with an SAE who has agreed to participate in the study will be reassessed by the 
investigator to see if they still meet the inclusion criteria. If the patient no longer meets the criteria, 
they will be removed from the study.  
The risk of an SAE being attributable to our intervention is very low because it does not directly 
impact patient care. 
Each participant who presented an SAE attributable or not to the studied procedure will be 
analyzed by the investigator. The investigator will attempt to identify the reason for the SAE in 
each case by consulting the patient's physicians and will document it in the patient's CRF. If the 
SAE is caused by a drug, the investigator will declare a pharmacovigilance announcement. 
 
6.3 (Periodic) Safety Report 
An annual safety report will be submitted once a year to the local ethics committee by the 
investigator (ClinO, Art. 43 Abs) if applicable for this type of study. 
6.4 Amendments 
Substantial changes in study set-up and organization, protocol, and relevant study documents 
are subject to approval by the Ethics Committee prior to implementation. In emergency 
circumstances, deviations from the protocol to protect the rights, safety and welfare of human 
subjects may be made without prior approval of the Ethics Committee. Such deviations should be 
documented and reported to the Ethics Committee as soon as possible. 
A list of all non-substantive changes will be submitted annually to the appropriate EC with the 
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6.5 (Premature) study termination 
The sponsor and the principal investigator may terminate the study prematurely under certain 
circumstances, such as 
- 
Ethical issues, 
- 
Insufficient recruitment of participants, 
- 
When participant safety is in doubt or at risk (e.g., when the benefit-risk assessment is no 
longer positive), 
- 
Changes in accepted clinical practice that make it unwise to continue the study, or 
- 
Early evidence of harm or benefit from the experimental intervention. 
In the event of the regular termination of the study, the ethics committee is informed via BASEC 
within 90 days (ClinO, art. 38).  
In the event of premature termination or interruption of the study, the ethics committee is informed 
via BASEC within 15 days (ClinO, art. 38). 
6.6 Insurance 
In case of damage or injury related to the study, the University Hospitals of Geneva is liable for 
compensation, except for claims resulting from fault or gross negligence.  
 
7 
OTHER ASPECTS 
7.1 Other ethical considerations 
This trial will be able to generate results that will be important in the field of patient education. We 
want to evaluate whether the intervention of a hospital pharmacist with heart failure patients on 
their knowledge can have a positive impact on their health behavior. Offering patients the 
opportunity to access information on these high value-added drugs during their hospital stay 
seems to us to be essential in order to ensure the best possible long-term adherence to taking 
these drugs. If the results of this study show that the patient's knowledge, beliefs and adherence 
to treatment are improved, then these teaching interviews could be offered to all patients with 
heart failure in the hospital. This will allow the deployment of other interventions for other chronic 
conditions. If the results are negative, the reasons for this failure will be identified and evaluated 
in order to readjust the pharmacist's interventions to improve patients' knowledge and therapeutic 
adherence. 
This study offers any hospitalized patient with heart failure who is being treated with medication 
a new tool to improve their health knowledge while receiving quality care from the hospital. This 
care will not be altered by this study.  
 
7.2 Risk-benefit assessment  
 
There is no risk of harm to patients by participating in this study.  
The pharmaceutical intervention does not present any risk to the patient in the sense that it does 
not alter the patient's therapeutic management in any way. The project does not discourage any 
treatment or any change in the usual management of the patient by the medical and nursing staff. 
This project even reinforces the care of the hospital medical and nursing team by educating the 
patient on his or her pathology and follow-up. It gives them the tools to take ownership of their 
disease and become autonomous in their follow-up. The participants will be able to benefit from 
the trial. 

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8 
QUALITY CONTROL AND DATA PROTECTION 
8.1 Quality measurement  
For quality assurance, the sponsor, the ethics committee or an independent trial monitor may visit 
the research sites. Direct access to source data and all study-related files is granted on these 
occasions. All parties involved keep participant data strictly confidential. 
 
 
 
8.2 Data recording and source data 
All baseline data will be assessed with the medical record consultation, with the patient himself 
at the time of inclusion if not referenced in the computerized patient record or with the hospital 
physician in charge of the patient. These data as well as the results of the knowledge score, 
adherence beliefs and satisfaction surveys, the follow-up questionnaire, exploratory measures of 
CardioMeds usability® and self-care skills will be captured and physically stored in mySQL ver.7.x 
for REDCapTM . An electronic clinical data management system, a CDMS (Clinical Trial Data 
Management System). This software is validated by the HUG clinical research center for data 
management. 
Ongoing data from the study will be stored, queried, viewed, cleaned and exported through this 
CDMS. 
 
All research subject data will be coded to ensure confidentiality using a combined letter and 
number identifier. The data collected for each research subject will constitute a Case Report Form 
(CRF), which contains the following elements 
- Inclusion criteria and consent 
- Demographics 
- Medical data (history, co-morbidities, laboratory tests, medications) 
- Knowledge, adherence and belief questionnaires in pre-test and post-test as well as satisfaction 
questionnaires, follow-up questionnaire, exploratory measures of CardioMeds usability® and self-
care skills measures 
- Questionnaire Scores 
 
- Adverse events 
 
The collection of clinical data is done through the electronic case report form (eCRF) that will be 
created with REDcapTM .  
 
The source documents are all the original documents related to the study, i.e. the research 
protocol, the ethics committee agreement, the original consent form signed by each participant 
and the CRF extraction. These will be stored in a study-specific file cabinet. 
 
The identification data of the participants such as name, first name, date of birth, date of stay and 
any other data that can be used to identify a patient will be stored in an Excel file. This file will be 
stored in a computer file on the common and secured server of the HUG pharmacy. Access to 
this file will be strictly limited to the investigator and the file will be locked with a code accessible 
only by the investigator. 
8.3 Privacy and Encryption 
Trial and participant data will be treated with the utmost discretion and will be accessible only to 
authorized personnel who need the data to perform their duties in the study (investigator and 

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clinical research associate). On CRFs and other study-specific documents, participants are 
identified only by a unique participant number.  
 
Storage: 
The identification list of participants will be kept in a secure manner (see §8.2 data recording and 
source data) 
 
For the duration of the study, the data will be stored in the CDMS, REDcapTM, which can only be 
accessed by the investigator and a research assistant with a personal login and password.  
 
All paper source data will be available in a dedicated study cabinet. This cabinet will be stored in 
the pharmacy's clinical trials office. All other source documents will be stored electronically, in the 
pharmacy's secure network, accessible only by the principal investigator and his/her research 
assistant.  
 
Access to the database will be available to the study investigator and research assistant only 
during the inclusion process, but also during the data analysis phase and after the study is 
completed. Access will be password protected to prevent unauthorized access. 
 
Once the data is collected and the REDCapTM database is complete, the data will first be extracted 
into an Excel spreadsheet. This will be stored in the pharmacy's secure network.  
For the statistical analysis, the data of interest will be prepared for transfer to the statistician of 
the Methodological Support Unit, so that he can import them into the statistical software he will 
use. A do-file will be used to store all the statistics produced. 
 
Where possible, we will store files in open archive formats, such as Word files converted to PDF-
A or simple text files encoded as UTF-8 files and Excel files converted to CSV. If this is not 
possible, we will include information about the software used and its version number. 
8.4 Retention and destruction of study data and biological materials 
At the end of the project, the final research data collected will be extracted from RedcapTM and 
stored for archiving for 10 years. This means on the hospital's servers in a folder with limited 
access to the investigator and the sponsor for the electronic data and in a locked cabinet in the 
pharmacy for the paper documents related to the clinical study (study binder).  
The data archives will also be deposited either in an appropriate database (data repository) 
managed by the University of Geneva (Yareta) or on a magnetic tape managed by the University 
of Geneva. 
 
9  MONITORING AND RECORDING 
The monitoring will be carried out in accordance with the ICH BPEC and coordinated by an 
internal auditor at the HUG pharmacy, Dr. Christel Bruggmann, trained in BPEC and in Clinical 
Research (CAS) and investigator of several clinical trials in the past. 
As the monitor for this project, she will conduct this monitoring by following a risk-adapted 
monitoring plan and written standard operating procedures. She will verify that the clinical trial is 
conducted and that data is generated, documented, and reported in accordance with the protocol, 
good clinical practices, and applicable regulatory requirements. The site initiation visit, several 
interim monitoring visits, and the site closeout visit will be arranged by the clinical site monitor. 

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The investigator will provide direct access to all trial-related source data/documents and reports 
for monitoring purposes. 
We will register the study in French in the Swiss National Clinical Trials Portal (SNCTP via 
BASEC) and in English in a WHO-recognized primary registry, such as the US ClinicalTrials.gov 
registry (as required by the WHO and the International Committee of Medical Journal Editors). 
10. FUNDING / PUBLICATION / DECLARATION OF INTEREST 
The investigator has no financial conflicts of interest. There is no financial compensation for 
participants for this study. This activity requires a full-time equivalent of 0.5. The source of funding 
is provided by the Pharmacy, as part of a doctoral thesis program. The clinical research associate, 
Mrs BOEHM-BOSMANI Cristina, will be paid by the HUG Pharmacy Service. A search for funding 
is underway with pharmaceutical companies to finance this position. They will have no influence 
on the content of the protocol and on the progress of the study. 
 
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