Association between use of desloratadine and risk of seizures, supraventricular tachycardia, and atrial fibrillation or flutter: A Nordic register-based study (MK-4117-205)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Observational case-study design with use of register-based data

Study drug and medical condition

• Medical condition to be studied:
  Seizure

  Supraventricular tachycardia

  Atrial fibrillation

  Atrial flutter

Population studied

• Short description of the study population:
  The cohort of individuals with redeemed DL prescriptions will be identified from the four Nordic national prescription registers. Similarly, the cohort of all individuals with seizures (first seizure), the cohort of individuals with SVT, and the cohort of individuals with A-fib/flu will be identified from the four Nordic national patient registers. The population is comprised of all individuals with DL prescriptions and of all individuals with seizures, SVT, or A-fib/flu in the four Nordic countries in the period 2001–2015 in Denmark and Finland, 2008–2015 in Norway, and July 2005–2015 in Sweden.; Inclusion criteria; Substudy 1; - Individuals who have redeemed at least one prescription of DL during the study period (DL cohort) and have residential location in Denmark, Finland, Norway, or Sweden.; - General population living in Denmark, Finland, Norway, and Sweden on 01 January of each year.; Substudy 2A; - Individuals who have experienced a seizure during the study period (seizure cohort) and have residential location in Denmark, Finland, Norway, or Sweden.; - General population living in Denmark, Finland, Norway, and Sweden on 01 January of each year.; Substudy 2B; - Individuals who have redeemed at least one prescription of DL during the study period (DL cohort) and have residential location in Denmark, Finland, Norway, or Sweden.; Substudy 3A; - Individuals who have experienced a SVT during the study period (SVT cohort) and have residential location in Denmark, Finland, Norway, or Sweden.; - General population living in Denmark, Finland, Norway, and Sweden on 01 January of each year.; Substudy 3B; - Individuals who have redeemed at least one prescription of DL during the study period (DL cohort) and have residential location in Denmark, Finland, Norway, or Sweden.; Substudy 4A; - Individuals who have had an A-fib/flu diagnosis during the study period (A-fib/flu cohort) and have residential location in Denmark, Finland, Norway, or Sweden.; - General population living in Denmark, Finland, Norway, and Sweden on 01 January of each year.; Substudy 4B; - Individuals who have redeemed at least one prescription of DL during the study period (DL cohort) and have residential location in Denmark, Finland, Norway, or Sweden.; Exclusion criteria; Substudy 2A; - Individuals with a diagnosis of seizure, epilepsy, or prescriptions of antiepileptic medicine before entering the study period, as they have prevalent disease. ; - Individuals with a diagnosis of malignant brain tumor or head trauma before the first seizure, as they are at high risk of seizures due to causes other than DL use.; Substudy 2B; - Individuals with a diagnosis of seizures, epilepsy, prescriptions of antiepileptic medicine, malignant brain tumor, or head trauma before redemption of first DL prescription, as they have prevalent disease or are at high risk of seizures due to causes other than DL use.; - Individuals with a brain tumor (benign and malignant), initiation of treatment with antiepileptic medicine, or head trauma occurring after beginning of DL use will be censored at date of first occurrence, as they are at high risk of seizures due to causes other than DL use.; Substudies 3A and 4A; - Individuals with a diagnosis of SVT or A-fib/flu before entering the study period, as they have prevalent disease.; - Individuals with a diagnosis of congenital pre-excitation syndrome (e.g., Wolff Parkinson White) before entering the study period, as they are at high risk of cardiac SVT or A-fib/flu due to causes other than DL use.; Substudies 3B and 4B; - Individuals with a diagnosis of SVT or A-fib/flu before use of DL, as they have prevalent disease.; - Individuals with a diagnosis of congenital pre-excitation syndrome (e.g., Wolff Parkinson White) before use of DL, as they are at high risk of SVT or A-fib/flu due to causes other than DL.
• Age groups:
  • Term newborn infants (0 – 27 days)
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 46 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Seizure, supraventricular tachycardia, or atrial fibrillation or flutter patients
• Estimated number of subjects:
  365500

Study design details

• Main study objective:
  The objective is to explore the use of desloratadine (DL) in the general population, to describe the incidence rate (IR) and examination of association between DL exposure and first seizure, first SVT, first A-Fib/A-Flu.
• Outcomes:
  IR of first seizure diagnosis, first SVT diagnosis, and first A-Fib/A-Flu diagnosis in patients administered DL
• Data analysis plan:
  A descriptive analysis of DL use in the general population will be performed. Furthermore, the incidence rates of seizure, SVT, A-Fib/A-Flu, and first recurrent seizure will be calculated. Among persons ever dispensed DL, the associations between DL exposure and first seizure, SVT, A-Fib/A-Flu, and first recurrent seizure will be evaluated using Poisson regression of incidence rates accounting for confounding factors. Additional supplementary analyses will be performed.