EMR200101_502: Incidence and pattern description of gastrointestinal, skin, genital, corneal, and mucosal erosions, ulcerations, perforations, haemorrhages, fistulas, abscesses, delayed wound healing and death among patients treated with nicorandil with and without diverticular disease

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  IKOREL
• Medicinal product name, other:
  Dancor, Adancor, Nicorandil Zentiva, Angicor
• Study drug International non-proprietary name (INN) or common name:
  NICORANDIL
• Anatomical Therapeutic Chemical (ATC) code:
  (C01DX16) nicorandil

  nicorandil
• Medical condition to be studied:
  Angina pectoris

Population studied

• Short description of the study population:
  Adult patients registered in NHS who have a diagnosis of angina pectoris between April 1995 to November 2014 and receive an initial Nicorandil prescription.
• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 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:
  Patients with angina pectoris
• Estimated number of subjects:
  40000

Study design details

• Study design:
  This is a retrospective cohort study, featuring accrual exposure assessment, i.e. each included patient will contribute his/her own person-time in the analysis data cut. In this study design, and to maximize the sample-size, patients can be included at various time points in the database
• Main study objective:
  The primary purpose is to determine the time-related frequency (i.e. the incidence) and patterns of Perforation, Ulcer, Fistula, Abscess, Erosion, Diverticulosis, Diverticulitis, Death, Delayed wound healing, hemorrhages (PUFAEDH) in patients with angina who are receiving Nicorandil treatment.
• Setting:
  This study will be conducted using the Clinical Practice Research Datalink (CPRD), including data collected by General Practitioners of 681 practices around the UK accounting for 13 million total patients, 5.7 million of which are currently active. This is a patient-level data study including any individual aged 18 years registered in the NHS seen in a representative sample of primary practises in the UK. CPRD being part of the NHS, the data collection is systematic and the language used (READ codes) very specific. The database includes demographics, lifestyle (BMI, smoking habits, alcohol consumption, dietary guidance), diagnostics, prescriptions and procedures over time for any citizen registered into the NHS and over time. The longitudinal aspect of the licensed segment ; of the database (1995-2014) allows for an almost optimal capture of any patient treated in a designated geographic area, provided that the drug was launched in the UK in 1994.
• Outcomes:
  Incidence Rates: The incidence rates will be calculated using the number of patients presenting with an outcome of interest and the number of events of interest divided by the number of person-years at risk between the index date and the end date of the exposure period, and linked to the event or patterns of events of interest. The secondary analytic phase will concentrate on patients who had a first PUFAEDH within the 3 months before first Nicorandil prescription (prevalent condition during the baseline period) versus those who did not. Incidence rates for further unique or multiple PUFAEDH and their 95% CI per 100,000 person-years, in patients using Nicorandil will be calculated.
• Data analysis plan:
  Descriptive analytics will be provided for the following variables: age, gender, Nicorandil dose, treatment duration, calendar year, Charlson´s comorbidity index, history or existence of any outcome of interest, diabetes, Helicobacter pylori infection, Zollinger-Ellison syndrome, smoking and use of NSAIDs (including acetylsalicylic acid), diverticular disease, heart failure, alcohol use, use of corticosteroids, selective serotonin re-uptake inhibitors (SSRIs), trauma, impaired blood circulation, bacterial, viral or fungal infections, tumours. Continuous variables will be summarized as average, standard deviation, median, Q1 and Q3. Dichotomous variables will be summarized as sums, proportions and percentages.