Cohort Study of the Incidence of Major Cardiovascular Events in New Adult Users of Lisdexamfetamine and Remote Adult Users of Other ADHD Treatments

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/43216
• EU PAS number:
  EUPAS20546
• Study ID:
  43216
• Official title and acronym:
  Cohort Study of the Incidence of Major Cardiovascular Events in New Adult Users of Lisdexamfetamine and Remote Adult Users of Other ADHD Treatments
• DARWIN EU® study:
  No
• Study countries:
  Denmark

  Sweden
• Study description:
  This study will consist of multiple observational (non-interventional) population-based cohort studies of patients initiating Lisdexamfetamine dimesylate (LDX) compared with patients with remote use of other attention deficit and hyperactivity disorder (ADHD) medications, in three electronic health care data sources: the Danish National Registries, and the Swedish National Registers. The main objective of this study is to estimate the incidence rate (IR) and the adjusted incidence rate ratios (IRRs) of the composite major adverse cardiovascular events (MACE) endpoint in a cohort of adult patients who are current new users of LDX compared with a cohort of remote users of other ADHD treatments. Current use for LDX new users is defined as the duration of the LDX prescription or dispensing plus 30 days. The remote use of other ADHD treatments will be generated by selecting adult patients with at least one prescription/dispensing for a medication indicated for ADHD, other than LDX, during the 24 months prior to the index date and with no prescriptions or dispensings of these medications in at least the last 180 days before index date. The analysis will be conducted separately in each data source, and overall estimates of effect will be obtained using meta-analytic techniques as appropriate. The primary endpoint, MACE, will comprise the first occurrence of any of its individual components during follow-up: hospitalisation for acute myocardial infarction, fatal or non-fatal, hospitalisation for stroke, fatal or non-fatal, out-of-hospital coronary heart disease death, and out-of-hospital cerebrovascular death. Secondary endpoints are an extended MACE (EMACE) endpoint that includes hospitalisation for either unstable angina or TIA, the composite coronary and stroke components of EMACE, and an additional secondary endpoint that will be a composite of sudden cardiac death and serious ventricular arrhythmias.
• Study status:
  Finalised

Research institutions and networks

Institutions

RTI Health Solutions (RTI-HS)

France

Spain

Sweden

United Kingdom

United Kingdom (Northern Ireland)

United States

Centre for Pharmacoepidemiology, Karolinska Institutet (CPE-KI)

Sweden

RTI Health Solutions (RTI-HS)

France

Spain

Sweden

United Kingdom

United Kingdom (Northern Ireland)

United States

Study timelines

Date when funding contract was signed

Planned: 01/06/2017

Actual: 01/06/2017

Study start date

Planned: 01/12/2019

Actual: 30/09/2019

Date of final study report

Planned: 30/06/2020

Actual: 18/12/2020

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Shire Human Genetic Therapies, Inc., a wholly owned subsidiary of the Takeda Pharmaceutical Company Limited

Study protocol

Initial protocol

0304010 - LDX Protocol Final Version (v2.0)- 08March2016_redacted

Updated protocol

LDX protocol_final version 3.0_final_3Jun2019_Redacted

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  EU RMP category 2 (specific obligation of marketing authorisation)