Mind your medication: A randomized, controlled trial using a TELEmedicine solution to improve MEDication adherence in chronic Heart Failure (TELEMED-HF)

The syndrome of systolic heart failure arises as a consequence of impaired
cardiac pump function, and is a constellation of relatively nonspecific signs
(e.g., edema, tachycardia) and symptoms (e.g., fatigue, breathlessness).
Epidemiologic evidence shows that the prevalence of symptomatic heart failure
is 6-10% in the elderly population, and is growing due to successful treatment
of myocardial infarction and increased survival after an acute cardiac event.
These patients are likely to end up with chronic heart failure (HF), and
consequently have a more frequent need for rehospitalization, and poorer
survival chances. Heart failure is therefore associated with major healthcare
costs, e.g., in 2005 almost 390 million Euros were spent on heart failure care,
and it is expected that these costs increase with the ageing population.
Pharmacological treatment of HF typically consists of a combination of >=4
different types of medication. A major problem in heart failure management is
poor medication adherence (only 50-70% of patients are adherent), which may to
a great extent explain frequent readmissions in HF patients, as well as being
associated with increased morbidity and mortality. Hence, improving medication
adherence may enhance cardiac prognosis, reduce the number of heart
failure-related hospital readmissions, improve quality of life and increase
survival, and reduce healthcare costs. A recent longitudinal study showed that
adherence rates above 88% were associated with a decreased number of
rehospitalizations and mortality rates than patients who are less adherent. In
this study, objective medication adherence was measured using an electronic
chip in the medication cap (*Medication Event Monitoring*; MEMS) that records
each moment the cap is removed from the medication bottle.

A novel tool to improve patient adherence is telemonitoring, permitting remote
patient monitoring, either by structured telephone support, or using special
telecare devices in conjunction with a telecommunication system that
electronically transfers patient data. To date, few randomized controlled
trials have studied the efficacy of telemonitoring to improve adherence in HF
patients, and have yielded mixed findings. One study reported a clinically
relevant improvement in some health behaviours using a health buddy®
intervention, while another failed to reduce HF-related hospitalization or
cardiac death by weekly transmissions of vital signs and telephone contact.
Conversely, weekly assessment of patients* clinical status by home
telemonitoring was associated with better medication adherence, and reduced
mortality and hospitalizations. However, these results were based on small
samples (<110), and most were time-consuming as the intervention involved
telephone support. Further, only one small study tried to improve medication
adherence using a specific adherence device (i.e. a medication box transferring
data to an electronic record), finding that this device improved patients*
compliance. However, this study did not examine the effect of the device on the
clinical course of heart failure. Another recent study showed that home
telemonitoring was associated with a significant increase in the use of
beta-blockers, an essential medicine in congestive heart failure, and lower
mortality rates and less rehospitalizations in the telemonitoring group than
the control group5.

When trying to improve patient adherence, it is important to examine potential
adherence modifiers. These can be of a clinical and pharmacological nature,
i.e. disease characteristics and medication side-effects may cause people not
to take their medication, but they may also be of a psychosocial nature.
In effect, socio-economic status, social support, and patient related factors
such as self-care behaviour, motivation, mood, and personality may affect
medication adherence in heart failure patients. Previous studies on clinical
and psychosocial factors that may affect medication adherence in HF failed to
find determinants of adherence. However, these were all drug trials in which
adherence was around 90%, which is not representative of the heart failure
populations in general in which adherence to medication is around 50%.

In summary, medication adherence in chronic heart failure patients is poor and
previous studies have not clearly demonstrated which method(s) is/are effective
in improving medication adherence, ultimately improving the patient*s
prognosis.

The current proposal wants to examine the efficacy and cost-efficiency of a
telemonitoring solution to improve medication adherence in chronic heart
failure patients, to enhance the clinical state of the patients and to reduce
health care consumption, while assessing the moderating roles of psychosocial
factors on medication adherence. Specifically, we propose a randomized
controlled trial (RCT) that examines the efficacy and cost-efficiency of a
novel Medication Adherence Monitor (MAM) to improve medication adherence. This
device not only dispenses all prescribed medication in the right dosage at the
specified times, but also records adherence, reminds patients to take their
medication (alarm, SMS or voicemail), and importantly, sends critical data
about non-adherence to the HF nurse. The first aim of this RCT is to examine
the efficacy of this device to enhance medication adherence in patients with
HF. In addition, this study will examine the correspondence between objectively
assessed adherence and self-reported medication adherence in these HF patients.
Further, it is the aim of this RCT to examine clinical, demographic and
psychological factors that may modulate the effect of MAM. This would delineate
distinct profiles of patients who benefit from this intervention, and those who
may not, and would help to tailor self-management programs to patients'
individual needs.
Finally, as the effects of the implementation of a medication-specific
adherence device on the clinical course of heart failure are yet unknown, the
proposed RCT also aims to examine the effect of any changes in medication
adherence on disease progression, physical functioning, quality of life and
health care consumption in a large group of patients with HF.

This is a randomized controlled clinical trial with two conditions, i.e. an
intervention arm and usual care arm, with a 12-month follow-up period. After a
6-month intervention period (see below for intervention), all patients continue
to receive usual care, and participate in 4 follow-up occasions at 3-, 6-, 9-
and 12-months post-intervention. These follow-ups coincide with regular clinic
appointments and involve questionnaire assessments and a 6-minute walk test.
The follow-up at 3 and 9 months will consist of a telephone call, only
requesting information on healthcare consumption and adherence. Over the
18-month study period, retrospective refill rates are requested from the
patients* pharmacies.

The timeline of one participant in the study is as follows: after inclusion,
the participants visit the heart failure nurse for their usual care visit.
Participants in the treatment group then receive the medication adherence
monitor and are instructed how to use it at the hospital pharmacy after the
usual care visit. The intervention takes 6 months. During the intervention
period, at 3 and 6 months usual care visits to the heart failure nurse take
place. After completion of the intervention follow-up assessments take place at
3, 6, 9 and 12 months post-intervention. In total, the study duration for a
participant is 18 months.

Based on the availability of patients visiting the outpatient clinic, weekly,
six participants can in theory be included in the control condition and three
in the treatment condition. With 80 medication adherence monitors at our
disposal, we will be able to carry out the above-mentioned inclusion rate,
resulting in a total duration of the inclusion period of 1.5 to 2 years. The
final patient thus will have finished the study 3 to 3.5 years after the start
of the study.

Intervention: The intervention consists of the use of an electronic Medication
Adherence Monitor for a 6-month period as well as 2 visits to the heart failure
outpatient clinic of the TweeSteden hospital (usual care). This monitor (a)
dispenses all prescribed medication in the right dosage at the specified time,
(b) reminds patients to take their medications through an alarm, sms or
voicemail service and records adherence, and (c) sends critical data about
non-adherence to the heart failure nurse, via a web application (CarebyWeb).
The Medication Adherence Monitor is provided to the patient by the hospital
pharmacy, including an instruction how to use the device. After the
intervention patients return to usual care only. We expect a training effect,
with continued improved adherence in the intervention group.

Participation is considered to be safe, as patients will keep receiving the
same medication as before, only in a different package, i.e. the MAM instead of
regular, prescribed medicine boxes. The hospital pharmacy or patients* own
pharmacy will ensure the delivery of the medication to the participants* homes
for the duration of the intervention, depending on which organization of
pharmacies they belong to. This is dealt with at the level of the pharmacy
supplier, so the patient will be minimally burdened with this. Participation in
the treatment group may be beneficial because of improved adherence to
medication, but also may induce medication side effects (due to taking all
their medications in prescribed dosages).