Heart Failure Educational and Follow up Platform
Heart Failure Educational and Follow up Platform
Heart failure is a serious and common disease. HF is marked by a high rate of preventable
 hospitalizations through proper care. As such, it is a key target for telemedicine programs.
 However, currently published data are inconclusive. Investigators propose a multicenter
 randomized study of innovative telemedicine involving the usual patient monitoring daily
 weight monitoring, clinical signs and in one of three groups in our study of BNP testing in
 the patient's home all associated with a regular education reinforcement. The objective is to
 identify early cardiac decompensation to allow to treat ambulatory and thus prevent the
 occurrence of more serious events such as death or rehospitalization.
Chronic heart failure (CHF) is a disease that has several specificities. It is both common
 and severe. This is a disease associated with high mortality and especially a high rate of
 hospitalization. These are partly due to the severity " per se "of the disease but also to
 the non optimal management of CHF and non-formal education of patients and their caregivers.
 Indeed, the majority of hospitalized patients shows some clinical signs of decompensation up
 to 5 days before hospitalization and could avoid to go to the emergency room and
 hospitalization by an adequate ambulatory reaction and care. It is on this premise that
 underlies the concept of the application of telemedicine in CHF. Telemedicine is the
 monitoring of biological or clinical data in the patient's home with the transfer of
 information remotely either to a specific structure often managed by nurses or to the GP or
 cardiologist.

 In most studies of telemedicine, effectiveness of the concept is based on the notion of
 monitoring of some markers with low sensitivity or specificity. This monitoring generates a
 lot of information which, because of the better education of the patient and from its
 systematic examination or through technology (internet, phone, SMS) or through remote
 monitoring of the nurse often leads to detection of sources of unnecessary hospitalization
 and offset the advantage gained in the early detection of decompensation. In addition, the
 low sensitivity and specificity of clinical signs generate many warnings that cause difficult
 remote management by the patient and the doctor. BNP is a blood biomarker recognized as
 having a high negative predictive value for the diagnosis of CHF and the rate change was
 correlated with a change in the prognosis. Its dosage is conventionally performed in
 peripheral blood using POCT devices or not. More recently, it is possible to perform the
 dosage by the patient itself at home, including a satisfactory feasibility.

 This is why, in the HELP study , Investigators wanted to study the impact of the addition of
 BNP measurement at patient's home to a innovative device for telemedicine monitoring
 combining patient perception of clinical signs of HF decompensation, daily weight monitoring
 and strengthening patient education but also specific training of doctors by E learning in
 order to promote implementation of the ESC recommendations.

 Study hypotheses

 The primary objective of the HELP study is to determine the impact of a tele monitoring
 strategy based on either a telemonitoring of the weight associated with an educational
 reinforcement (clinical monitoring arm) or on the same track associated with a BNP assay at
 home performed by the patient every week and in case of symptoms suggestive of decompensation
 (bioclinical monitoring arm) on a primary endpoint including death from all causes,
 unscheduled re-hospitalization or CHF admission to the emergency department compared to a
 control group (usual monitoring arm).

 Be secondarily analyzed the impact in terms of re-hospitalizations, deaths emergency
 admissions, the number of false positives (unconfirmed suspected cardiac decompensation),
 false negatives (undetected cardiac decompensation), the effect of monitoring quality of life
 and economic impact of these medical strategies.

 Study design, inclusion, and exclusion criteria HELP (n° ansm 2013-A00899-36 ) is a
 multicentric, prospective, open label, randomized, ambulatory study. The authors are solely
 responsible for the design and conduct of this study, all study analyses, the drafting and
 editing of the paper, and its final contents. HELP study benefit form a specific grant of the
 Ile de France regional health agency, France. The aim was to initially include 330 patients
 suffering from ambulatory CHF according to inclusion and exclusion criteria Study procedures
 Patients should be followed by the study investigators. After signing the informed consent
 (approval by a French legal ethical committee on 8 th October 2013 N° 2013-A00899-36-3101),
 patients will be randomized into three arms according to their type of CHF (systolic CHF and
 CHF with preserved systolic function defined by the coexistence of signs of CHF and an
 ejection fraction> 45%). Patients will therefore be included into a standard of care arm
 (placebo group), one arm followed by clinical and telemonitoring arm ( Cordiva System (R)
 arm) followed by bio-clinical monitoring (BNP and Cordiva (R) monitoring system arm) .
 Patients will be seen per protocol at inclusion and 3, 6, 9 and 12 months after inclusion.

 -  Placebo arm group: Patients will be managed per consensus guidelines Clinicians could
 see the patients as many times as necessary in order to optimize their therapy and could
 make BNP measurement (but not using Home BNP monitoring)

 -  Cordiva System (R) arm : Patient will see their cardiologist every three months and
 benefit from telemonitoring of their weight and general well being through a specific
 communicant device. Patients have to answer to 8 specific binary questions based on the
 main precipitating factors for decompensation and measure their body weight every day.
 If not they will be contact after two missing measures. Patient will be contact by phone
 call every month in order to reinforce the initial patient therapeutic education and
 patient-'s compliance. Patient have access to specific printed documents and to a
 specific web based platform where he can find some PowerPoint presentation on CHF
 aetiology, signs and therapy and where he can try to answer to monthly quiz in whom
 questions are based on key messages about CHF according to guidelines and consensus
 paper on patient therapeutic education. The cardiologist has access to a specific
 platform. In this platform they could find the E CRF of their patients and the patient
 's quiz result in order to help him to analyse patient comprehension of HF and patient
 reactivity in case of decompensation. The cardiologist could also find some PowerPoint
 presentation on CHF and AHF management according to ESC guidelines. He could also read
 the monthly report of the telemonitoring nurse and the daily results of weight and
 general being measurement of his patients.

 -  BNP and Cordiva (R) monitoring system arm : In this group, patients and doctors have
 access to the platform detailed above and had also access to BNP home monitoring.
 Patients had to measure the BNP plasma level using Alere home based BNP device
 heartcheck in a weekly basis in order to follow this parameter up. In case of clinical
 signs of CHF or a significant weight increase identified by the tele monitoring or the
 patient, the nurse will ask to the patient to do an extra measurement of home BNP
 testing in order to exclude a CHF decompensation (BNP < 100 pg/ml or remaining stable (<
 30% increase).

 End Points

 Primary end point is a composite end point including Unplanned hospitalizations for CHF with
 hospital stay > 1 day / all-cause death / non-programmed emergency department admission
 related to CHF.

 Secondary endpoint are based on an analysis of the impact of the strategy used in the two
 interventional arms compared to the placebo group for:

 -  each parameter of the composite end point analyzed separately

 -  emergency admission.

 -  Number of all cause death.

 -  Number of HF hospitalizations

 -  Patient management

 -  Adherence to the strategy

 -  Quality of life.

 -  False positive induced by the system (visits to the GP or cardiologist proposed by the
 telemonitoring system without final evidence of HF decompensation and without increase
 of diuretics )

 -  Medical cost and efficience of the technique

 -  Cost of the different strategies

 -  Cost efficacy of the different strategies

 Hospitalization for heart failure was defined per protocol by an in-hospital stay of more
 than one night in addition with intravenous use of diuretics.

 Statistical analysis Events in the three groups were analyzed using parametric student t
 test. Percentages were compared using Chi2 tests. Kaplan Meier time to event function for
 readmission or death from any cause were calculated. For each end point, investigators also
 estimated the hazard ratio and 95% confidence interval using a Cox proportional-hazards To
 calculate sample size, analyzing recent clinical trial data, investigators expected at least
 40% of SOC subjects will have at least one cardiovascular event within 1 year. Assuming a 40%
 reduction in the occurrence of the primary end point in the telemonitoring groups ,
 investigators estimated that a sample size of at least 110 subjects in each group would
 provide 80% power (α = .05) for detection of a reduction in primary end point. An initial
 goal enrollment of 330 subjects was proposed. According to the event rate in the control
 group study size could be secondarily extended to 600 patients.

 Sub group analysis Actual prespecified sub group analysis were defined according to some
 patients characteristics or locations : Investigators also tested for interactions between
 each pair of subgroups and the main treatment effect.

 Age (cut off 65 y old ) and above and below median value. PSEF versus REF (defined by EF >
 45%) aetiology of CHF as defined by the investigator High symptomatic patients vs low
 symptomatic patients according to NYHA class Heart failure units management (defined by the
 investigator as working in such a structure) vs all others High neurohormonal activation
 patients vs low neurohormonal activation defined as initial BNP higher or lower than 300
 pg/ml and in an second analysis by median initial BNP value.

 patient adherence to the " phone call system " (<75% vs. ≥75%) BNP Compliant vs non compliant
 patients defined by an compliance to daily measurement plus BNP measurement in BNP group
 higher than 80%.

 Highly implicated vs low implication patients defined according to the monthly connection to
 the patient site and median value during the study.

 Good HF education level vs low HF education patients defined by tertile value of quiz
 performance (global, knowledge and situation questions as isolated value).
Inclusion Criteria:

 -  Heart failure diagnosed on a first hospitalization for acute exacerbation during the
 last twelve months, without high age limit

 -  Men or women

 -  More than 18 years old

 -  Minimal knowledge of the French language (patient or his relatives)

 -  The patient need to fill an informed written consent

 -  Patient resides or is treated in Ile de France

 -  Patient is insured under the social security system

 Exclusion Criteria:

 -  Myocardial infarction or revascularization or Heart Valve Surgery < 3 months

 -  Inability to execute the feasibility test

 -  Major cognitive disorders do not allow access to the platform

 -  Patient does not have the necessary autonomy to use the equipment

 -  Sensitive subject, under Article L32 of the Code of Public Health

 -  Patient enrolled in another clinical trial

 -  Renal failure with creatininemia clearance (cockcroft) <15 ml/min

 -  24h/day oxygen