An integrated personalised assistive devices approach to reduce the risk of foot ulcer recurrence in diabetes (DIASSIST)

Globally, every 20 seconds a lower limb is lost due to diabetes. Most
amputations are preceded by a foot ulcer, which in itself has a lifetime risk
up to 34% and annual incidence rate of 2.2% in persons with diabetes. In
particular, the risk for ulcer recurrence is high: 40% within one year after
healing. Ulcers and amputations are key outcomes of diabetic foot disease, that
ranks 10th in leading causes of global disease burden, and have a significant
negative impact on quality of life and patient mobility. Furthermore, the
treatment of these foot ulcers is costly, due to high risk of infection,
including hospitalization, and amputation, and amounts to about ¤10.000 per
ulcer episode. Thus, ulcer prevention is an important means to decrease this
patient and healthcare burden.

Foot ulcers are caused by repetitive stress due to weight-bearing activity,
that goes unrecognized because of loss of protective sensation due to
neuropathy. To prevent plantar foot ulcer recurrence, guidelines recommend an
approach consisting of multiple modalities, including: custom-made shoes with a
demonstrated plantar pressure-relieving effect that is constantly worn by the
patient, patient and family education, regular foot inspection and care, and
instructing patients to perform self-management by means of monitoring their
own foot temperature. Nevertheless, ulcer recurrence rates remain high.

For these high recurrence rates, a variety of potential explanations can be
given. First, above recommendations are likely insufficiently implemented, as
these multiple modalities are currently provided by a variety of healthcare
professionals in an unstructured and uncoordinated approach. Lack of insight in
costs and effectiveness of these modalities plays a role in this insufficient
implementation, as these interventions have only been studied from the
perspective of a single modality, but never from a multi-modal intervention
perspective, and no cost-utility or cost-effectiveness studies are available.
Second, even when implemented, modalities are not of state-of-the-art quality
in daily practice. For example, state-of-the-art knowledge on effective
custom-made footwear designs is frequently not part of clinical practice, and
patient education in practice is unstructured and non-personalised. Third,
non-adherence to preventative treatment by patients is high, which reduces
effectiveness of the interventions. For example, non-adherence to wearing
prescription custom-made footwear is particularly high when patients are in
their house, due to the perception of the footwear being heavy, difficult to
don and doff, warm and dirty, and because of habit. Additionally, if patients
perceive their footwear as less beneficial, footwear will be worn less
frequently. Also, patients sense the daily self-management required for ulcer
prevention as a burden, and daily thermometry adds to that burden, explaining
some of the low adherence to that intervention seen in the only study that
reported this outcome. To overcome these reasons and to better help prevent
ulcer recurrence in diabetes, a state-of-the-art multimodal ulcer prevention
intervention is needed, and its cost-utility, cost-effectiveness and effects on
patient adherence should be investigated.

Primary Objectives
To assess, as primary economic outcome measure, cost-utility of a personalised
multimodal orthotic treatment approach to reduce the risk of plantar foot ulcer
recurrence in diabetes.
And, as primary patient-related outcome measure, to assess adherence to wearing
custom-made footwear following a personalised multimodal orthotic treatment
approach to reduce the risk of plantar foot ulcer recurrence in diabetes.
And, as primary clinical outcome measure, to assess foot ulcer recurrence
following a personalised multimodal orthotic treatment approach.

Secondary Objectives
To assess cost-effectiveness, plantar foot ulcer recurrence, foot ulcer
recurrence at high-risk locations, costs, quality-adjusted life years,
ulcer-free survival days, time to ulceration, cumulative plantar tissue stress,
plantar pressure, physical activity, wearing time, serious adverse events,
treatment satisfaction, quality of life, footwear usability, footwear
wear-and-tear, ulcer risk, foot-related self-care, knowledge of foot care, and
(in case of ulceration) referral time, time to healing and ulcer severity,
following a personalised multimodal orthotic treatment approach to reduce the
risk of plantar foot ulcer recurrence in diabetes.

The study design of the current study is a multi-centre single-blinded (outcome
assessor) parallel-group randomized controlled trial with two study arms:
1. Multimodal care, which includes usual care as provided in the Netherlands
and, in addition, a personalised multimodal orthotic treatment approach
(experimental group).
2. Usual care as provided in the Netherlands (control group).

Setting of the study:
Recruitment will take place from three university or community-based hospitals
with a multidisciplinary diabetic foot clinic in different regions in the
Netherlands, and from professional practices of podiatrists who participate in
the multidisciplinary team. Each diabetic foot clinic will operate as one of
the study centres where all the study assessments take place. Within each
centre, a physician, podiatrist and an orthopaedic shoe technician will be
involved. The participating hospitals are: Amsterdam UMC (location AMC and
location VUmc), Maxima Medisch Centrum (Veldhoven), Reinier de Graaf Gasthuis
(Delft).

Some parts of multimodal care may take place at the patient*s home or via
telephone.

Duration of the study:
Patients who consent to participate will be randomized to multimodal or usual
care. Each participant will be followed for 12 months. Participants who have an
ulcer or active Charcot's neuroarthropathy at 12 months will be followed for
another 6 months or until two weeks after healing (whichever comes first), to
obtain cost and healing outcomes associated with that ulcer.

The treatment of participants who are randomized to multimodal care will
consist of usual care, and in addition a personalised state-of-the-art
multimodal orthotic treatment approach that contains:

• Custom-made shoes, evaluated and optimized using in-shoe pressure analysis,
and re-evaluated after 6 months
• Custom-made indoor shoes for specific use indoors, also pressure-optimized
and evaluated over time
• Personalised at-home daily foot temperature monitoring at high-risk regions
• Personalised patient education consisting of quantitative feedback on in-shoe
pressures, temperature measurements and footwear use and, in addition,
motivational interviewing where indicated and needed to improve device use

The intervention in this RCT is *multimodal care*. This multimodal care
consists of 4 modalities. While all these modalities can, theoretically, be
offered to individual participants as part of usual care, their combined
prescription is unique and currently not available in the Netherlands or
anywhere globally. Moreover, in the current study the intervention does not
only consist of the four modalities, but applies these in a structured and
strictly protocolled manner, ensuring that all participants will receive
state-of-the-art care. And, lastly, the four modalities are offered in a
personalised approach, to match the individual participant*s clinical situation
and personal needs. With that, this intervention differs from usual care, where
some of these modalities might be offered, but unstructured, without
state-of-the-art protocols, and without personalised approach.

There are no known risks for the participants in this study. By participating
in the study, foot status may be checked more regularly in the multimodal care
group. Participation in the trial will give insight into the cause of the
arising foot problems in the patient. Positive outcomes on multimodal care
could lead to further integration of in the intervention in Dutch Health Care.