Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04727476 |
| Other study ID # |
LDX-2013-2019 |
| Secondary ID |
IIR-DNK-002529 |
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 19, 2021 |
| Est. completion date |
May 1, 2022 |
Study information
| Verified date |
August 2021 |
| Source |
Aarhus University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Aiming at improving clinical practice regarding the use of lisdexamfetamine for the treatment
of ADHD in children, the investigators want to retrospectively map the clinical use of
lisdexamfetamine at a specialised outpatient clinic located at Aarhus University Hospital,
Denmark treating children aged 7-13 with Attention Deficit Disorders in the period from 2013
to 2019. The investigators will describe the changes in prescription practice in the period,
reported side effects and reasons for selecting and discontinuing treatment with
lisdexamfetamine.
Description:
Background
Attention deficit hyperactivity disorder (ADHD) is characterised by the core symptoms of
inattention, hyperactivity and impulsivity, which are excessive for the person's age and
developmental status. It is a clinical diagnosis based on observed and reported behavioural
symptoms. Two main diagnostic systems are used currently, the International Classification of
Diseases 10th revision (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders
5th edition (DSM-5). Both systems require presence of symptoms in several settings such as
school, home life and leisure activities as well as the presence of functional impairment due
to symptoms of ADHD (e.g. impairment of psychological, social and/or educational
functioning). Symptoms should be evident in early life; for ICD-10 by age 7 and for DSM-5 by
age 12. Overall, the diagnostic criteria of ADHD are less stringent according to DSM-5
compared to ICD-10, which is reflected by a higher prevalence of ADHD in populations where
the DSM-5 diagnostic criteria are applied. A systematic review (Sayal et al.) from 2018 of 55
studies (25 from the USA, seven from the UK, and 23 outside the USA and UK) reported a
prevalence of ADHD in children and adolescents varying from approximately two to seven
percent depending mostly on the diagnostic criteria, making it one of the most common
psychiatric disorders in children and adolescents.
In Denmark the ICD-10 diagnostic system is used. The National Institute for Health and Care
Excellence (NICE) as well as The National Clinical Guidelines from the Danish Health
Authority recommend pharmacological treatment for children and adolescents with moderate to
severe ADHD. Severity is determined by a clinical assessment based on number of symptoms and
functional impairment. Both guidelines recommend the use of methylphenidate (MPH) as the
first choice of treatment. In the event that the use of MPH is non-effective in an adequate
dosage or results in adverse effects, it is recommended to switch to atomoxetine (ATX),
dexamfetamine (DX) or lisdexamfetamine (LDX). The subsequent choice of medication should take
into consideration the adverse effect profiles and duration of effect of the different drugs
as well as the reason for the switch.
In February 2013, Elvanse (LDX) received marketing authorization in the UK and Europe. It
became available for sale for the treatment of ADHD in children and adolescents in Denmark in
April 2013.
LDX is an inactive prodrug which is gradually activated to DX by means of peptidase enzymes
in the red blood cells. Thus, LDX is a controlled-release drug where a single dose has an
effect on the ADHD core symptoms for up to 13 hours. The formulation as a prodrug reduces its
potential for abuse. According to www.medstat.dk which is based on data from the Danish
Register of Medicinal Product Statistics (LSR), the sales of lisdexamfetamine has been
steadily increasing during the years it has been on the market in Denmark.
In our clinical experience medical treatment of ADHD in children is often complicated by
intolerable adverse effects (e.g. weight loss due to loss of appetite or disturbance of
sleep), worsening of symptoms of comorbidities (e.g. anxiety, tic disorders or psychosis),
lack of/inadequate effect or non-optimal day coverage of treatment. In our experience, these
complications often lead to frequent switches in medical treatment. This is supported by a
study by Ben Amor et al. (2014) in which the authors reported a one-year period prevalence of
switching from one stimulant to either another stimulant, ATX or atypical antipsychotic of
19.5% in children and 17.4% in adolescents.
Another study by Warrer et al. (2016) reported that the mean duration of MPH treatment before
switching to ATX was 11.2 months in a population of 55 children and adolescents aged 7-18
years with attention deficit disorders. 36% of the patients switched within the first 6
months, 56% within the first year and 76% within 1.5 years. 24% continued with MPH for 2.5
years before switching to ATX. The most common reasons for switching were adverse effects
(78%), need for stable 24-hr effect (24%) or lack of effect (16%). The conclusion of this
study as well as the conclusion of another study by Powell et al. (2011), was that the
importance of continuously evaluating the treatment of the individual patient throughout the
entire course of treatment needs to be emphasised, especially if there is no immediate good
effect and tolerability of the first choice of medication.
Aiming at improving clinical practice regarding LDX, the investigators want to describe the
changes in prescription practice in the period 2013 to 2019, reported side effects and
reasons for selecting or discontinuing LDX. The investigators expect LDX to be prescribed
more often in later years compared to earlier years because clinicians may be inclined to a
select medical treatment they have experience with rather than a new one.
Hypotheses Hypothesis 1: The investigators expect LDX to be second choice in line with ATX in
later years.
Hypothesis 2: The investigators expect the main reasons for switching to LDX to be adverse
effects from MPH and/or ATX. The investigators expect to be able to describe top 5 adverse
effects.
Hypothesis 3: The investigators expect patients who continue treatment with LDX to be
comparable with patients who discontinue treatment with LDX regarding gender, age, diagnosis,
ADHD symptoms at baseline and comorbidities.
Hypothesis 4: The investigators expect adverse effects to be the main reason for
discontinuing LDX.
To our knowledge, there are no previous studies investigating the practical clinical use of
LDX in Denmark.
Method
The study is a retrospective descriptive study that includes data from medical records of
approximately 600 patients.
Patients will be identified in the electronic patient record system based on the inclusion
criteria. Baseline data and outcome data will be extracted from medical records by Nanna Roed
Søndergaard, MD, who will enter the data into a REDCap database designed for this purpose.
Patients will be categorised into three groups according to whether they have received
treatment with LDX as a first, second or third choice of treatment. Combination treatment
will also be registered.
Descriptive statistics will be used to summarise overall patient and treatment
characteristics, duration of therapy to switches, clinical reasons for switches in therapy,
clinical effect and adverse effects observed. Comparison between groups will be performed
using parametric or non-parametric test. An alfa level will be set at 0.5 in all analyses.
Analyses will be conducted using the statistical software program Stata 15.
In accordance with Danish legislation the study has been approved by the Danish Health and
Medicines Authority, registered at the Danish Data Protection Agency and will be conducted in
accordance with the Danish Act on Processing of Personal Data. This study requires no patient
contact. It will not be possible to trace the results of the study back to individual
patients. Data will be stored in MidtX in agreement with the EU General Data Protection
Regulation (GDPR). According to Danish legislation, no ethics or institutional review board
approvals are required for this study.
