Clinical trial NCT04575103: Monitoring of Arrhythmias in Patients Treated With Antipsychotics
Official title: Monitoring of Arrhythmias in Patients Treated With Antipsychotics - The MAPP II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Death, Sudden, Cardiac
Arrythmia
Antipsychotics and Neuroleptics Toxicity
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Bispebjerg Hospital
name: Nordsjaellands Hospital
name: University Hospital, Gentofte, Copenhagen
name: Zealand University Hospital
name: Odense University Hospital
name: Aarhus University Hospital
name: Aalborg University Hospital
First posted: 2020-10-05
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Antipsychotics may be associated to life-threatening arrhythmias and sudden cardiac death. This is the fist study to estimated the arrhythmic burden using long-term monitoring by implantable loop recorder in patients treated with antipsychotics.

Detailed description: Aims and objectives To estimate frequency of potential malign arrhythmias and cardiovascular outcome in a population with patients treated with antipsychotic drugs compared to healthy controls.

Background Life expectancy is about 20 years shorter for patients with mental illness compared to the general population. Increasing evidence suggest that antipsychotic drugs can cause cardiac arrhythmias and hence sudden death. However, the evidence as well as the incidence of rhythm disturbances in patients treated with antipsychotic drugs is insufficient reported. Prolonged monitoring with external portable monitors is difficult for practical and technical reasons. In addition, long-term consistent and structured timing of clinical visits is often a challenge in this vulnerable patient group. In recent years, patients who have been suspected of rarely occurring arrhythmias, have been offered long-term monitoring using an 'implantable loop recorder' (ILR). However, no study has evaluated the arrhythmic burden in patients treated with antipsychotic drugs using ILR.

Methods and materials The study is a national joint project between departments of psychiatry and cardiology across Denmark. After written informed consent and a baseline evaluation including echocardiography, ecg and biochemistry, an ILR will be implanted. During follow-up, arrhythmias will be monitored at regular clinical visits. Cardiovascular endpoints will be monitored using Danish national registries.

Expected outcome and perspectives The present study is the first to reveal arrhythmias among patients treated with antipsychotics using consistent long-term monitoring. The results will give valuable insights into possible mechanism of the observed early death and risk of sudden death in patients treated with antipsychotics.

Eligibility criteria: Inclusion Criteria:

* Patients with SMI defined according to ICD-10 as:

  * F20.0-F20.9 schizophrenia
  * F22.0-F22.9 paranoid psychosis
  * F25.0-F25.9 schizo-affective psychosis
  * F28 other non-organic psychosis
  * F29 non-organic psychosis unspecified
  * F31.0-F31.9 bipolar affective disorder.
* Patients treated with or initiating antipsychotics with ≥ 0.5 daily defined dosage
* \>18 years old and \<50 years.

Exclusion Criteria:

* Patients not capable to understand the aim of the study as judged by investigator.
* Current in treatment with methadone.
* Left ventricular hypertrophy (echocardiographic septal thickness ≥1.3 cm for women and ≥1.4 cm for men, or LVM/BSA ≥109 g/m2 for women or ≥132 g/m2 for men).
* Heart failure (echocardiographic LVEF \<35%).
* Ischemic heart disease (patient reported coronary bypass grafting or percutaneous coronary intervention.
* Congenital cardiovascular disease (patient reported).

Primary outcomes:
measure: Ventricular arrhythmias
timeFrame: 2 years from insertion og loop recorder
Secondary outcomes:
measure: Supraventricular arrhythmias
timeFrame: 2 years from insertion og loop recorder
measure: Bradycardia
timeFrame: 2 years from insertion og loop recorder
Other outcomes:
measure: Long QT interval
timeFrame: 2 years from insertion og loop recorder
measure: Pacemaker/ICD implantation.
timeFrame: 2 years from insertion og loop recorder
measure: Sudden cardiac death.
timeFrame: 2 years from insertion og loop recorder
measure: Cardiovascular mortality
timeFrame: 2 years from insertion og loop recorder
measure: All-cause mortality
timeFrame: 2 years from insertion og loop recorder
measure: Suicide or death caused by non-cardiac factors
timeFrame: 2 years from insertion og loop recorder
measure: Frequency of primary endpoint in controls
timeFrame: 2 years from insertion og loop recorder
measure: Frequency of primary endpoint related to specific psychiatric drugs / dose
timeFrame: 2 years from insertion og loop recorder
measure: Frequency of primary endpoint related to the presence of long QTc interval
timeFrame: 2 years from insertion og loop recorder
measure: Frequency of primary endpoint in poor metabolizers compared to normal metabolizers
timeFrame: 2 years from insertion og loop recorder
measure: Frequency of primary endpoint by genetic analysis
timeFrame: 2 years from insertion og loop recorder
Locations:
city: Aabenraa
country: Denmark
facility: Department of Psychiatry, Region of Southern Denmark
city: Aalborg
country: Denmark
facility: Cardiology, Aalborg Universitetshospital
city: Aalborg
country: Denmark
facility: Psychiatry, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital, Skejby, Department of Cardiology
city: Aarhus
country: Denmark
facility: Department of Psychiatry, Aarhus University
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital, Department of Cardiology
city: Copenhagen
country: Denmark
facility: Copenhagen Center of Psychiatry (Rigshospitalet)
city: Copenhagen
country: Denmark
facility: Mental Health Center Amager
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Department of Cardiology
city: Frederiksberg
country: Denmark
facility: Mental Health Center Frederiksberg
city: Gentofte
country: Denmark
facility: Gentofte-Herlev Hospital, Department of Cardiology
city: Glostrup
country: Denmark
facility: Mental Health Center Glostrup
city: Hellerup
country: Denmark
facility: Mental Health Center Copenhagen
city: Hillerød
country: Denmark
facility: North Zealand Hospital, Department of Cardiology
city: Hillerød
country: Denmark
facility: North Zealand Hospital, Department of Psychiatry
city: Odense
country: Denmark
facility: Odense University Hospital, Department of Cardiology
city: Roskilde
country: Denmark
facility: Zealand University Hospital, Department of Cardiology
city: Slagelse
country: Denmark
facility: Psychiatric Research Unit, Region of Zealand
Study officials:
affiliation: Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Copenhagen University, Denmark
name: Casper Bang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: