title: Drug-induced QT prolongation when QT interval is measured in each of the 12 ECG leads in men and women in a thorough QT study.
abstract: Lead II is commonly used to study drug-induced QT prolongation. Whether other ECG leads too show comparable QT prolongation is not known. We studied moxifloxacin-induced QT prolongation in a thorough QT study in healthy subjects (54 males, 43 females). Placebo-subtracted change from baseline in QTc corrected by Fridericia's method (ΔΔQTcF) at 1, 1.5, 2 and 4 hours after moxifloxacin was studied in all 12 leads. Unacceptably wide 90% confidence interval (CI) for ΔΔQTcF was seen in three leads; these leads also had maximum ECGs with flat T waves (60% in aVL, 45% in lead III and 42% in V1). After excluding ECGs with flat T waves, 90% lower CI of ΔΔQTcF was ≥ 5 ms in all leads except leads III, aVL and V1 in men. The 90% lower CI exceeded 5 ms in these leads in women despite wide 90% CIs because of greater mean ΔΔQTcF. Leads III, aVL and V1 should be avoided when measuring QT interval in thorough QT studies.
authors.affiliation: Quintiles Cardiac Safety Services, Mumbai, India. Electronic address: Gopi.Panicker@quintiles.com.
authors.forename: Gopi Krishna
authors.initials: GK
authors.lastname: Panicker
authors.affiliation: Quintiles Cardiac Safety Services, Mumbai, India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Salvi
authors.affiliation: Quintiles Cardiac Safety Services, Mumbai, India.
authors.forename: Dilip R
authors.initials: DR
authors.lastname: Karnad
authors.affiliation: Quintiles Cardiac Safety Services, Mumbai, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Quintiles Cardiac Safety Services, Mumbai, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Manohar
authors.affiliation: Quintiles Cardiac Safety Services, Mumbai, India.
authors.forename: Yash
authors.initials: Y
authors.lastname: Lokhandwala
authors.affiliation: Quintiles Cardiac Safety Services, Mumbai, India.
authors.forename: Snehal
authors.initials: S
authors.lastname: Kothari
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D064368:Healthy Volunteers; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D010919:Placebos; D012680:Sensitivity and Specificity
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D010919:Placebos; D000077266:Moxifloxacin
keywords: Assay sensitivity; Cardiac repolarization; Gender differences; Pharmacodynamics