Feasibility of the Use in Spanish Hospitals of Recommended Standards to Measure Results in Patients With Heart Failure (HF-Outcomes-Spain)
Conditions: Heart Failure
Sponsor: Fundacion Profesor Novoa Santos

 
 
 
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Feasibility of the use in Spanish hospitals 
of recommended standards to measure 
results in patients with heart failure  
(HF-Outcomes-Spain) 
 
July 22, 2020 - version 1.0 
 
 
 
 
 
 
PROTOCOL 
 
 

 
 
 
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SUMMARY 
 
1. Promoter 
Fundación Profesor Novoa Santos. A Coruña.  
 
2. Funding source 
Vifor Pharma España, S.L. 
 
3. Title of the study 
FEASIBILITY OF THE USE IN SPANISH HOSPITALS OF RECOMMENDED STANDARDS TO 
MEASURE RESULTS IN PATIENTS WITH HEART FAILURE (HF-OUTCOMES-SPAIN) 
 
4. Principal investigator 
Dra. Maria Generosa Crespo Leiro 
 
5. Scientific Committee 
Dra. Maria Generosa Crespo Leiro  
Dra. Beatriz Díaz Molina 
Dr. José Manuel García Pinilla 
Dr. Julio Núñez Villota 
Dr. Josebe Goirigolzarri Artaza 
Dra. Ainara Lozano Bahamonde 
Dr. Javier Muñiz García 
 
6. Participating centres and investigators 
6 participant centres: 
 
Complejo Hospitalario Universitario de A Coruña  
 
Hospital Universitario Central de Asturias  
 
Hospital Universitario Virgen de la Victoria, Málaga  
 

 
 
 
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 
Hospital Clínico Universitario de Valencia  
 
Hospital Clínico San Carlos de Madrid  
 
Hospital Universitario de Basurto, Bilbao-Vizcaya 
 
7. Clinical Research Ethics Committee (CREC) 
Comité de Ética de la Investigación de A Coruña-Ferrol 
 
8. Main goal 
To evaluate through a pilot study the viability of establishing and maintaining for one 
year in selected Spanish centers the set of standards for measuring results in patients 
with heart failure proposed by ICHOM (International Consortium for Health Outcomes 
Measurement). (International Consortium for Health Outcomes Measurement). 
 
9. Specific goals 
To identify factors that hinder the use and applicability of this group of standards in 
real life, where appropriate, defined as the variables not filled in and the reason for the 
absence of such information 
To estimate the workload necessary to implement this set of variables within everyday 
clinical practice.    
 
10. Study design 
Follow-up observational pilot study 
 
11. Study population 
Consecutive patients with a diagnosis of heart failure, either acute or chronic, treated 
by  a cardiologist and recruited in a short period of time (maximum, 3 weeks of 
inclusion). A maximum inclusion of 600 patients recruited from 6 Spanish hospitals 
(100 patients in each center) is expected.  
 
 
 
 

 
 
 
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12. Chronogram 
 
Preparation of documentation and protocol: July 2020 
 
Presentation to the ethics committee: July 2020 
 
Permissions and development of data entry platform: October 2020 
 
Recruitment and 30-day visit: April-May 2021 
 
First data analysis (debugging, exporting and labeling and analysis oriented to the 
preparation of a manuscript): September 2021 
 
Closure of follow-up (visit of 6 months and 1 year and intermediate events): 
April-May 2022 
 
Database closure, export, debugging, data analysis oriented to the preparation of 
a manuscript: September 2022. 
 
 
13. Promoter and Coordinator Centre Data 
Promoter: 
Fundación Profesor Novoa Santos. A Coruña.  
 
Coordinating Centre: 
ODDS, S.L. 
c/ Wenceslao Fernández Flórez, 1-2º 
15005 La Coruña  
 
 
 
 
 

 
 
 
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SUMMARY 
 
1. Background and rationale 
6 
2. Goals 9 
 
2.1. Main goal 
9 
 
2.2. Specific goals 
9 
3. Study design 
9 
 
3.1. Definition of the study population and selection criteria 
9 
 
 
3.1.1. Selection of centres 
9 
 
 
3.1.2. Selection of patients 
10 
 
 
3.1.1.1. Inclusion criteria 
10 
 
 
3.1.1.2. Exclusion criteria 
10 
 
 
3.1.1.3. Types of patients 
11 
 
3.2. Sample size considerations a 
11 
 
3.3. Variables and CRD (appendix 1) 
12 
 
3.4. Data source 
12 
 
3.5. Follow-up 
15 
4. Data collection and management 
16 
5. Plan for data analysis 
16 
6. Ethical and security issues 
16 
7. Practical issues 
18 
 
7.1. Information to patients 
18 
 
7.2. Working plan and chronogram 
18 
 
7.3. Dissemination of results 
18 
 
7.4. Study organization 
19 
 
7.4.1. Responsibilities of the participating researchers 
19 
 
7.4.2. Responsibilities of the Coordinating Center 
19 
 
7.4.3. Functions of the scientific committee 
20 
 
 

 
 
 
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PROTOCOL 
 
1. BACKGROUND AND RATIONALE  
Cardiovascular diseases pose a significant burden for the health system and for the 
population as a whole throughout the world (1). In the case of heart failure, the end 
result of a variety of cardiovascular diseases, its weight has been increasing 
progressively in recent years, particularly the burden on the health system, with a 
notable increase in the number of admissions and being the main cause of admission 
for those over 65 and with enormous associated economic costs. The prevalence that 
has been estimated in Spain is around 1% in the age group 45-54 years and increases 
rapidly in the following decades to around 15% in those older than 75 years (2). In the 
future, it is foreseeable that the burden will continue to increase, so good monitoring 
of its evolution is important, as well as those measures that improve its management.  
The clinical practice guidelines of heart failure recommend treatments that affect the 
course of the disease, in particular mortality, hospitalization or some intermediate 
events such as ejection fraction or ventricular remodeling (3), and also recommend the 
organization of care of these patients based on heart failure units (4-5). Subjective 
aspects of the patient, such as the reduction of symptoms and improvements in quality 
of life are increasingly important and recognized in heart failure, but there is less 
agreement on how to measure these aspects that are reported by the patients 
themselves (6). This makes international comparisons difficult and limited in these 
important respects. There have been multiple proposals in the past to identify a 
minimum set of variables to monitor in order to assess the quality of care received by 
patients with different cardiovascular conditions. Very recently, the International 
Consortium for the Measurement of Health Outcomes (ICHOM) developed a proposal 
in heart failure (7) in which a standard set of patient-centered outcomes is defined in 
order to improve patient care and allow comparison between regions and health 
systems, in line with others previously developed in other cardiovascular conditions 
(8). This set of standard results is intended to be both a management and a research 
tool. Its development sought to collect enough data to produce valuable information 
for the indicated purposes and, at the same time, from a pragmatic point of view, 

 
 
 
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reduce the quantity and complexity of the information collected to the essential 
minimum to guarantee viability (based on the time and cost of its implementation) (7). 
The advantage of this initiative over previous ones is its international character and, in 
addition to including recognized experts in heart failure, epidemiology and public 
health, it also included health professionals from close disciplines and patient 
advocates and representatives. The same document in which the set of standards is 
proposed recognizes some difficulties that must be overcome for their application in 
real life in clinical practice (7), difficulties that are expected to vary between different 
settings and health systems and that have begun to be evaluated at least in Brazil on a 
pilot basis. Due to the importance of having standardized outcome measures that 
allow monitoring the quality of care for patients with heart failure and the workload 
involved, as well as comparing the results between centers and countries, and the 
relative advantages of the recent proposed by ICHOM, in this project it is proposed to 
carry out a pilot study to evaluate the feasibility of applying the aforementioned 
proposal in conditions of usual clinical practice in selected Spanish hospitals, of 
different geographical locations, which have a high level of activity in heart failure and 
with a heart failure unit in their organization. In addition to the availability of routine 
clinical practice, a few minimal resources are added that were considered essential 
from the start. 
 
 

 
 
 
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References 
1. Groenewegen A, Rutten FH, Mosterd A, Hoes AW. Epidemiology of heart failure. Eur 
J Heart Fail 2020. Doi:10.1002/ejhf.1858.  
2. Anguita Sánchez M, Crespo Leiro MG., de Teresa Galván E, Jiménez Navarro M, 
Alonso Pulpón L, Muñiz García J, en representación de los investigadores del estudio 
PRICE. Prevalencia de insuficiencia cardíaca en la población general española mayor de 
45 años. Estudio PRICE. Rev Esp Cardiol 2008; 61(10):1041-9  
3. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and 
treatment of acute and chronic heart failure. Eur J Heart Fail. 2016;18(8):891–975. 
4. Ambrosy AP, Fonarow GC, Butler J, et al. The global health and economic burden of 
hospitalizations for heart failure: lessons learned from hospitalized heart failure 
registries. J Am Coll Cardiol. 2014;63(12):1123–33. 
5.- Anguita-Sánchez M, Lambert-Rodríguez JL, Bover-Freire R, Comín-Colet J, Crespo-
Leiro MG, González Vílchez F et al.  Tipología y estándares de calidad de las unidades 
de insuficiencia cardiaca: consenso científico de la Sociedad Española de Cardiología. 
Rev Esp Cardiol 2016;69:940-950. 
6.- McDonagh TA, Blue L, Clark AL, Dahlström U, Ekman I, Lainscak M et al. European 
Society of Cardiology Heart Failure Association Standards for Delivering Heart Failure 
Care. Eur J Heart Fail. 2011;13:235-41. 
7. Burns DJP, Arora J, Okunade O, Beltrame JF, Bernardez-Pereira S, Crespo-Leiro MG 
et al. International Consortium for Health Outcomes Measurement (ICHOM): 
Standardized Patient-Centered Outcomes Measurement Set for Heart Failure Patients. 
J Am Coll Cardiol HF 2020;8:212-22. 
8. McNamara RL, Spatz ES, Kelley TA, Stowell CJ, Beltrame J, Heidenreich P et al. 
Standardized outcome measurement for patients with coronary artery disease: 
consensus from the international consortium for health outcomes measurement 
(ICHOM). J Am Heart Assoc. 2015;4:e001767. 
 
 

 
 
 
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2. GOALS  
2.1. Main goal 
To evaluate through a pilot study the viability of establishing and maintaining for one 
year in selected Spanish centers the set of standards for measuring results in patients 
with heart failure proposed by ICHOM (International Consortium for Health Outcomes 
Measurement). (International Consortium for Health Outcomes Measurement). 
2.2. Specific goals 
To identify factors that hinder the use and applicability of this group of standards in 
real life, where appropriate, defined as the variables not filled in and the reason for the 
absence of such information 
To estimate the workload necessary to implement this set of variables within everyday 
clinical practice.    
 
3. STUDY DESIGN 
Observational pilot study with prospective follow-up with data collection at 30 days, 6 
months and 1 year. 
Due to the defined objective, the methods used are, to a large extent, those proposed 
by ICHOM, except in those sections that may be slightly modified to adapt to the local 
situation. 
 
3. 1. Definition of the study population and selection criteria 
3.1.1. Selection of centers 
Six centers with experience and adequate organization (heart failure unit) and with a 
sufficient size have been selected to guarantee the recruitment of patients in a short 
period of time (around three weeks). The main justification was to seek, within the 
usual clinical practice, centers where, due to the organization and interest in heart 
failure, the chances of success of this initiative were greater. The participating centers, 
of different geographical location and autonomous community are: 
 
 

 
 
 
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 
Complejo Hospitalario Universitario de A Coruña  
 
Hospital Universitario Central de Asturias 
 
Hospital Universitario Virgen de la Victoria, Málaga  
 
Hospital Clínico Universitario de Valencia  
 
Hospital Clínico San Carlos de Madrid 
 
Hospital Universitario de Basurto, Bilbao-Vizcaya 
 
3.1.2. Selection of patients 
100 consecutive patients will be selected in each center with a diagnosis of heart 
failure.  
 
3.1.2.1. Inclusion criteria 
 
Patients aged 18 years or older. 
 
Diagnosed with heart failure: Clinical identification of signs and symptoms of heart 
failure and objective evidence of heart dysfunction (3). 
 
Acute presentation (first presentation or decompensation of already known HF, 
whether or not it causes hospital admission) or chronic (stable outpatients) 
 
Of any etiology  
 
Any value of the ejection fraction.   
 
Give informed consent to participate in the study. 
 
3.1.2.2. Exclusion criteria 
 
Patients whose first manifestation of heart failure is cardiogenic shock, in that first 
episode. Those patients who survived an initial episode of shock and remain in 
heart failure can be included once stabilized. 
 
Heart transplant patients 
 
Patients with long-lasting ventricular assist devices 
 
Patients with isolated right heart failure. 
 
Patients with onset of heart failure and whose cause can be corrected 
immediately (eg, acute ischemia) 

 
 
 
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3.1.2.3. Types of patients 
Based on the situation at the time of inclusion, five types of patients are defined that 
reflect different clinical situations and influence the necessary follow-up plan. 
A.  Hospitalized patients: 2 types  
1. A recent diagnosis (at that admission), that is, they did not previously have the 
diagnosis of HF 
2. Patients with a previous diagnosis of HF and who are admitted for an episode of 
decompensation of HF 
B. Outpatients: 3 types 
1. A recent diagnosis that is in the process of titration and / or compensation 
2. A previous diagnosis, that they have suffered a decompensation, either defined 
because they have had to go to the emergency room (and the diuretic treatment 
has been increased) or have been seen in the outpatient clinic for that reason. 
3. "Stable" patients attending a follow-up visit. A simple follow-up. 
 
 
Outpatient follow-ups must be narrower in situations in which the patient is more 
unstable (A.1, A.2 and B1 and B2), while in situation B3, follow-up may be more lax (in 
fact in some centers these patients are not even followed up in HF consultations, but 
only go to primary care). This is reflected later in the monitoring plan (section 3.5) 
 
3. 2. Sample size considerations 
For the main outcome, success is considered if the proportion of patients followed is ≥ 
70%. A random sample of 588 individuals is sufficient to estimate, with 95% confidence 
and a precision of +/- 3.5 percentage units, a population percentage that is expected to 
be around 75%. Six Spanish centers will participate and a recruitment target of 100 
consecutive patients is set, for a total of 600 patients in the study. In addition, these 
sizes in each center offer, accepting an alpha risk of 0.05, a power greater than 80% to 
detect statistically significant differences between two centers, assuming that a follow-
up of 75% of patients is achieved in one and 55% in the other..  

 
 
 
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3.3. Variables and CRF (appendix 1) 
The variables to be collected can be grouped into three large groups 
a.- Demographic variables and baseline health status, which will be used, 
basically, as adjustment variables in the analysis. Anemia and iron deficiency 
are added to all the proposals by ICHOM due to their interest as precipitant of 
decompensation and therapeutic implications.  
 b.- Treatment variables. Here are the recommendations of the clinical practice 
guidelines for variables that affect mortality, hospitalization, quality of life or a 
mixture of these. They include drug treatment, devices (invasive treatments) 
and rehabilitation. 
c.- Outcome variables (“HF outcome set”). It includes 17 outcomes (Table 1) 
that affect four areas: functional, psychosocial, burden of care, and survival. In 
turn, they are divided into two large groups, those reported by the clinician and 
those reported by the patient himself (PROM, acronym for "patient-reported 
outcome measure").  
 
3.4. Data source  
Table 1 lists the possible sources of data for the outcomes and Table 2 for the 
demographic variables and baseline health status (adjustment variables). Treatment 
variables are collected from the patient's medical history or report. 
 
 
 

 
 
 
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Table 1. List of outcomes, time of collection and suggested data source  
 
 
Burns, D.J.P. et al. J Am Coll Cardiol HF 2020;8:212-22. 
 
 
 
 
 
 

 
 
 
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Table 2. Risk adjustment variables 
 
 
 
 
 
 

 
 
 
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3.5.  Follow-up 
Figure 1 shows an example of evolution and moments in which each type of 
information must be collected. 
From the baseline or inclusion visit and afterwards, in newly diagnosed patients or in 
those recruited in an acute situation, follow-up visits at 30 days, 6 months and 1 year 
((patients A1 and A2 and B1 and B2 of section 3.1.2.3) .In patients who were included 
in a stable situation, the 30-day visit will not be carried out (patients B3 of section 
3.1.2.3) since doing so would unjustifiably complicate the follow-up, giving more work 
and discomfort to patients and health professionals. The outcomes reported by the 
patient (PROMs) in the visits every six months may be collected by telephone contact if 
the doctor, due to the stable situation of the patient, does not consider the face-to-
face visit necessary. Information will be collected at in the case of hospital admissions 
during follow-up, these admissions also set the “counter to zero” with regard to time 
for the following visits (30 days, six months…).  
 
Figure 1. Example of a schedule for measuring results 
 
 
 
 
 
 
 
To Index event* (baseline) of heart failure 
 Baseline characteristics 
 PROMs (patient-reported outcome measures) 
 Clinician reported outcomes 
 
(*) The index event represents the entry into the set. The different situations at entry are described in section 3.1.2.3) 
(**) This visit will NOT be done in stable patients (patients B3in section 3.1.2.3) 
30 days 
after the 
index 
event** 
6 months 
after the 
index 
event 
Acute admission 
(including 
complications) 
30 days 
after 
discharge 
6 months after the 
last hospital 
admission  (reset 
the clock 
Every 6 
months 
throughout 
life  
To 
Follow-up chronology from entry into the outcome, including variables to be measured at each time point.  

 
 
 
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4. DATA COLLECTION AND MANAGEMENT 
A data entry application will be enabled that will include filters to detect 
inconsistencies and anomalous data and alarms for patient monitoring. The data will 
be anonymized for all the people involved in the study except for the person in charge 
in each center, who will be able to identify their patients to enable follow-up.  
 
5. PLAN FOR DATA ANALYSIS 
Two data analyses are planned, one that includes the information from the baseline 
visit and the 30-day visit (in patients for whom it is indicated in the protocol) and the 
final one with all the information collected. In both cases, a global analysis and a 
comparison between centers (benchmarking) will be carried out. 
In line with the main objective of this pilot study, the main variables are the proportion 
of patients who remain in follow-up, the proportion of patients in whom follow-up is 
carried out, in terms of time, as planned, and the proportion of missing data in each 
one of the defined outcomes. 
The pilot's success criteria will be a follow-up> 70%, a proportion of missing data in the 
outcomes <10%. 
 
6. ETHICAL AND SECURITY ISSUES 
This study will be evaluated by the A Coruña-Ferrol Research Ethics Committee. The 
signature of the participating patients of the informed consent form (Annex 3) will be 
required. This study will be carried out, like all research on people, in accordance with 
the ethical requirements expressed in the Declaration of Helsinki and its subsequent 
amendments. The data protection regulations in force in Spanish legislation will be 
complied with. 
 
 

 
 
 
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Benefit-risk assessment for patients 
Since it is an observational study, participation does not pose any risk to patients. The 
study results could benefit from improving patient care outcomes in the heart failure 
population. 
 
Information to patients and informed consent (Annex 3) 
Information about the study will be provided to patients via a detailed information 
sheet. The doctor will answer all the doubts that may arise to the participants. All 
patients included will receive an informed consent form, which they will sign in order 
to participate. This will be obtained before starting any study procedure. This consent 
may be withdrawn at any time. 
 
Confidentiality of data  
The data necessary to carry out this study will be collected pseudonymised, that is, 
pseudonymisation is the processing of personal data in such a way that they cannot be 
attributed to an interested party without the use of further additional information 
(coding). In this study, only the research team of your health center will know the code 
that will allow to know the identity of each participant in order to be able to do the 
follow-up. The treatment, communication and transfer of data will be done in 
accordance with the provisions of the General Data Protection Regulation (Regulation 
(EU) 2016/679 of the European Parliament and of the Council, of April 27, 2016). 
 
 
 

 
 
 
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7. PRACTICAL ASPECTS 
7.1.- Information to patients 
One of the difficulties of this initiative is that, as a pilot study, the information and 
alarm collection system is not integrated into the information system of the centers. 
This integration is also difficult to do uniformly and each autonomous community, if 
necessary, would eventually choose the way to do it. For the identification of certain 
events (income, especially) it is key to know that the patient is in this initiative 
(something that will not be necessary in the future if its use eventually becomes 
widespread). To achieve this, information to patients and their knowledge of the 
initiative and their active participation is key. Therefore, in addition to the essential 
information to accept to participate in the study, the patient will be informed of the 
follow-up plan and of the need to notify their doctors in case of admission by means of 
information cards delivered at the time of inclusion in the study. 
 
7.2. Working plan and chronogram 
 
Preparation of documentation and protocol: July 2020 
 
Presentation to the ethics committee: July 2020 
 
Permissions and development of data entry platform: October 2020 
 
Recruitment and 30-day visit: April-May 2021 
 
First data analysis (debugging, exporting and labeling and analysis oriented to the 
preparation of a manuscript): September 2021 
 
Closure of follow-up (visit of 6 months and 1 year and intermediate events): 
April-May 2022 
 
Database closure, export, debugging, data analysis oriented to the preparation of 
a manuscript: September 2022. 
 
7.3. Dissemination of results 
The dissemination of results will be carried out prioritarily, but not exclusively, through 
the scientific meetings of the Spanish Society of Cardiology. 
The principal investigator commits to disseminate the results obtained in scientific 
media, always guaranteeing the confidentiality of personal data. Once the statistical 

 
 
 
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analysis is completed, a Final Results Report will be made, preferably in a format to be 
published in specialty journals and whose final version will be the responsibility of the 
Scientific Committee and the Technical Coordination of the study. Partial or global data 
of the study may be used in general publications or in national and international 
congresses with adequate reference to its origin. The main authorship will fall on those 
responsible for its preparation (Scientific Committee and / or Technical Coordination 
or designated investigator), including at least one author from each participating 
center, provided that the journal's publication regulations allow it and with the 
principal investigator in the position of last author. Participating researchers will be 
able to publish their individual data. In this case, the researcher / s will communicate it 
to the Scientific Committee of the study, including the communication / manuscript 
that is intended to be published at least 30 days before the presentation to the 
congress / meeting or journal. 
 
7.4. Study organization 
 
7.4.1. Responsibilities of the participating researchers 
- Accept and commit to carry out all the rules and procedures of the study 
- Facilitate data monitoring and quality controls that are carried out 
- Comply with the ethical and legal principles of clinical research 
- Collaborate with the scientific committee in what is requested for the good progress 
of the study 
 
7.4.2. Responsibilities of the Coordinating Center 
- Preparation of the protocol (together with the Scientific Committee) and data 
collection notebook 
- Keeping up to date and keeping a record of all study documentation. 
- To serve as a link between principal investigator, study investigators and study 
promoter. 
- Control of compliance with deadlines and work logistics 
- Study monitoring 

 
 
 
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- Preparation of intermediate and final reports in collaboration with the Scientific 
Committee. 
- General support for the coordination of the study 
 
7.4.3. Functions of the Scientific Committee 
Preparing the study protocol and the data collection notebook 
Reviewing the study documentation and the database. 
Evaluating the study results 
Reviewing data analysis and draw conclusions and publications