Safety study to quantify the risk of ulceration (including all sites of occurrence), and related events (including perforations, fistula, abscess and bleeding) and death among patients treated with nicorandil with and without diverticular disease

Date of Approval
Application Number
16_088
Technical Summary

The purpose of this study is to quantify the time-related risk and patterns of erosions, ulcerations, perforations, haemorrhages, abscesses, fistulae, delayed wound healing in patients treated with nicorandil (including gastrointestinal, skin, ocular, mucosal, anal; alone or in multiple locations), and death; together with the exploration of high risk subgroups, other risk factors, and a dose and time effect assessment.

This is a retrospective cohort study using the UK CPRD database. The inclusion criteria will be: patients aged 18 and older, with a diagnosis of angina pectoris between 01/01/1995 and 31/12/2014, and an initial prescription for Nicorandil. They will be longitudinally followed-up until end of observation period or death. Exposure will be determined individually for each patient. Outcomes of interest will include Perforation, Ulcer, Fistula, Abscess, Erosion, Diverticulosis, Diverticulitis, Death, Delayed wound healing, haemorrhages (PUFAEDH). Standard descriptive statistics, Kaplan-Meier time to event assessment and Cox proportional hazards modelling will be used. The main outcomes will be the incidence rates and 95% confidence intervals for the outcomes of interest, as stratified by variables. Additional descriptive analyses will be provided for specific subgroups, i.e. patients with discontinuation with and without treatment restart, and patients with sequence of events suggesting progression or reversibility.

Health Outcomes to be Measured

Perforations, Ulcer, Fistula, Abscesses, Erosions, Diverticulosis, Diverticulitis, Death, Delayed wound healing, Hemorrhages. Outcomes of interest have been identified using READ codes.

Collaborators

Sandra Guedes - Chief Investigator - Merck Healthcare KGaA (Merck Group)
Sandra Guedes - Corresponding Applicant - Merck Healthcare KGaA (Merck Group)
Juergen Zieschang - Collaborator - Merck & Co., Inc.
Sampada Gandhi - Collaborator - Genzyme - Sanofi Company
Shinichi Matsuda - Collaborator - Merck & Co., Inc.
Ulrike Gottwald-Hostalek - Collaborator - Merck Healthcare KGaA (Merck Group)