title: Baseline and new-onset morphologic ECG abnormalities in healthy volunteers in phase I studies receiving placebo: changes over a 6-week follow-up period.
abstract: Morphological ECG abnormalities occur in 5-12% healthy adults participating in early phase clinical trials. We retrospectively analyzed 16,472 12-lead ECGs recorded at multiple time points in 420 volunteers (282 males, 138 females; aged 18-76 years) randomized to receive placebo from 19 Phase I studies to see if some baseline ECG abnormalities may disappear or new abnormalities may appear during the study. One hundred forty-four (34.3%) subjects had abnormal baseline ECGs, of which 66 (44.8%) reverted to normal during follow-up. Of 276 (65.7%) subjects with normal baseline ECGs, 118 (42.8%) developed ECG abnormalities over the next 6 weeks. Common baseline abnormalities included sinus bradycardia, R wave transition abnormalities, right axis deviation, non-specific T wave changes and atrial premature complexes. On follow-up ECGs, prolonged QT interval, first-degree AV block, sinus bradycardia, short PR interval, and R wave transition abnormalities reverted to normal. Common new-onset abnormalities in subjects with normal baseline ECGs included sinus bradycardia, prolonged QT interval, non-specific T wave changes, R wave transition abnormalities, and sinus tachycardia. Thus, transient morphological ECG changes may occur in healthy volunteers possibly due to diurnal variation, effect of food, hormones, or autonomic changes. This should be considered when interpreting "treatment-emergent" ECG changes in clinical trials.
authors.affiliation: Quintiles Cardiac Safety Services, Mumbai, Maharashtra, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Hingorani
authors.forename: Dilip R
authors.initials: DR
authors.lastname: Karnad
authors.forename: Mili
authors.initials: M
authors.lastname: Natekar
authors.forename: Snehal
authors.initials: S
authors.lastname: Kothari
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Narula
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000453:epidemiology / Q000503:physiopathology*; D001919:Bradycardia / Q000453:epidemiology / Q000503:physiopathology; D017321:Clinical Trials, Phase I as Topic; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D064368:Healthy Volunteers; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013610:Tachycardia / Q000453:epidemiology / Q000503:physiopathology; D055815:Young Adult
keywords: clinical trials; electrocardiography; healthy population