Effect of Feminizing Hormone Therapy on QTc Interval: A Secondary Analysis of a Randomized Clinical Trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Angus LM
PROVIDER: S-EPMC10979315 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
Publications
Effect of Feminizing Hormone Therapy on QTc Interval: A Secondary Analysis of a Randomized Clinical Trial.
Angus Lachlan M LM Lin Tina T Leemaqz Shalem Y SY Cheung Ada S AS
JAMA network open 20240304 3
Similar Datasets
Project description:ImportanceAntipsychotic medications, often prescribed for delirium in intensive care units (ICUs), may contribute to QTc interval prolongation.ObjectiveTo determine whether antipsychotics increase the QTc interval in patients with delirium in the ICU.Design, setting, and participantsAn a priori analysis of a randomized clinical trial in medical/surgical ICUs within 16 centers across the US was conducted. Participants included adults with delirium in the ICU with baseline QTc interval less than 550 ms. The study was conducted from December 2011 to August 2017. Data analysis was performed from April 25 to August 18, 2021.InterventionsPatients were randomized 1:1:1 to intravenous haloperidol, ziprasidone, or saline placebo administered twice daily until resolution of delirium, ICU discharge, or 14 days.Main outcomes and measuresTwelve-lead electrocardiograms were used to measure baseline QTc before study drug initiation and telemetry was used to measure QTc before each subsequent dose of study drug. Unadjusted day-to-day changes in QTc were calculated and multivariable proportional odds regression was used to estimate the effects of antipsychotics vs placebo on next-day maximum QTc interval, adjusting for prespecified baseline covariates and potential interactions with sex. Safety end points, including the occurrence of torsade de pointes, were evaluated. All analyses were conducted based on the intention to treat principle.ResultsA total of 566 patients were randomized to haloperidol (n = 192), ziprasidone (n = 190), or placebo (n = 184). Median age was 60.1 (IQR, 51.4-68.7) years; 323 were men (57%). Baseline median QTc intervals across the groups were similar: haloperidol, 458.0 (IQR, 432.0-479.0) ms; ziprasidone, 451.0 (IQR, 424.0-472.0) ms; and placebo, 452.0 (IQR, 432.0-472.0) ms. From day 1 to day 2, median QTc changed minimally: haloperidol, -1.0 (IQR, -28.0 to 15.0) ms; ziprasidone, 0 (IQR, -23.0 to 20.0) ms; and placebo, -3.5 (IQR, -24.8 to 17.0) ms. Compared with placebo, neither haloperidol (odds ratio [OR], 0.95; 95% CI, 0.66-1.37; P = .78) nor ziprasidone (OR, 1.09; 95% CI, 0.75-1.57; P = .78) was associated with next-day QTc intervals. Effects were not significantly modified by sex (P = .41 for interaction). There were 2 occurrences of nonfatal torsade de pointes, both in the haloperidol group. Neither was associated with study drug administration.Conclusions and relevanceThe findings of this trial suggest that daily QTc interval monitoring during antipsychotic use may have limited value in patients in the ICU with normal baseline QTc and few risk factors for QTc prolongation.Trial registrationClinicalTrials.gov Identifier: NCT01211522.
| S-EPMC10804270 | biostudies-literature
Project description:Lower dialysate calcium (dCa) concentration and dialysate citric-acidification may positively affect calcification propensity in serum of haemodialysis (HD) patients. However, the accompanying lower ionized blood calcium concentration may lead to a prolonged cardiac action potential, which is possibly pro-arrhythmic. The aim of this study is to investigate the influence of citric-acid dialysate on the QT-interval corrected for heart rate (QTc) compared to conventional dialysate with different dCa concentrations. We conducted a four-week multicentre, randomized cross-over trial. In week one and three patients received acetic-acid dialysate with a dCa of 1.50 mmol/l (A1.5), in week two and four acetic-acid dialysate with a dCa of 1.25 mmol/l (A1.25) or citric-acid dialysate (1.0 mmol/l) with a dCa of 1.50 mmol/l (C1.5) depending on randomization. Patients had continuous ECG monitoring during one session in week one, two and four. The data of 13 patients were available for analysis. Results showed a significant though limited increase of QTc with C1.5 (from 427 to 444 ms (start to end); p = 0.007) and with A1.25 (from 431 to 449 ms; p < 0.001), but not with A1.5 (from 439 to 443 ms; p = 0.13). In conclusion, we found that the use of C1.5 or A1.25 is associated with a significant prolongation of QTc which was however relatively limited.
| S-EPMC8110800 | biostudies-literature
Project description:BackgroundA Food and Drug Administration (FDA) safety communication in August 2011 warned that citalopram was associated with a dose dependent risk of QT prolongation and recommended dose restriction in patients over the age of 60 but did not provide data for this age group.MethodsCitAD was a randomized, double-masked, placebo-controlled, multicenter clinical trial for agitation in Alzheimer's disease (AD). Participants were assigned to citalopram (target dose of 30 mg/day) or placebo in a 1 ∶ 1 ratio. 186 people, 181 of whom were over the age of 60, having probable AD with clinically significant agitation were recruited from September 2009 to January 2013. After the FDA safety communication about citalopram, ECG was added to the required study procedures before enrollment and repeated at week 3 to monitor change in QTc interval. Forty-eight participants were enrolled after enhanced monitoring began.ResultsCitalopram treatment was associated with a larger increase in QTc interval than placebo (difference in week 3 QTc adjusting for baseline QTc: 18.1 ms [95% CI: 6.1, 30.1]; p = 0.004). More participants in the citalopram group had an increase ≥ 30 ms from baseline to week 3 (7 in citalopram versus 1 in placebo; Fisher's exact p = 0.046), but only slightly more in the citalopram group met a gender-specific threshold for prolonged QTc (450 ms for males; 470 ms for females) at any point during follow-up (3 in citalopram versus 1 in placebo, Fisher's exact p = 0.611). One of the citalopram participants who developed prolonged QTc also displayed ventricular bigeminy. No participants in either group had a cardiovascular-related death.ConclusionCitalopram at 30 mg/day was associated with improvement in agitation in patients with AD but was also associated with QT prolongation.Trial registrationClinicalTrials.gov NCT00898807.
| S-EPMC4051660 | biostudies-literature
Project description:BackgroundConcomitant medication use, including agents that prolong the corrected QT (QTc) interval, can result in the exclusion of patients with cancer from clinical trials. To estimate the potential effects on accrual, we determined the prevalence of QTc-prolonging medication prescriptions in a national patient cohort.Patients and methodsWe identified adult patients in the Veterans Affairs system with a diagnosis of lung cancer from 2003 to 2016. The use of QTc interval-prolonging medications and risk category were obtained from CredibleMeds. We calculated the prevalence of prescriptions for QTc-prolonging medications with a known or possible risk of torsade de pointes in the 3 months up to and including the date of cancer diagnosis. The rates across patient groups were compared using χ2 test.ResultsA total of 280,068 patients were included in the present study. The mean age was 70 years, 98% were male, and 72% were white. Overall, 28.4% had been prescribed a QTc-prolonging medication, and 7.3% had been prescribed ≥2 in the 3 months before the cancer diagnosis. The most commonly prescribed QTc-prolonging medications were antimicrobial agents (14.0%), psychiatric agents (10.2%), antiemetic agents (2.6%), and cardiac medications (1.7%). Excluding the antimicrobial agents, 18.4% of the patients had been prescribed a QTc-prolonging medication.ConclusionsA substantial proportion of individuals with lung cancer will be prescribed QTc-prolonging medications. These prescriptions can limit patients' eligibility for clinical trials and complicate the administration of standard cancer therapies. Further research into the actual clinical risks and optimal management of QTc-prolonging medications in cancer populations is warranted.
| S-EPMC6937372 | biostudies-literature
Project description:Because hormone therapy use benefits sleep, sleep problems may occur after suspension. We tested the effects of short-term hormone therapy suspension on sleep problems.A total of 1,704 women aged 45 to 80 years at Group Health were randomized to suspend hormone therapy for 1 or 2 months or to continue using hormone therapy. This study included 1,405 women willing to suspend hormone therapy use who returned both baseline and follow-up questionnaires, administered within approximately 3 months of randomization. We used generalized linear models to examine the relationships between hormone therapy suspension and nine individual items from a modified General Sleep Disturbance Scale (number of days experienced in the past week) and an overall sleep quality index at follow-up. We tested whether age, hormone therapy type, or duration of use modified these relationships.Suspension of hormone therapy for 1 or 2 months was associated with greater frequency of sleep problems for the overall sleep quality index and most individual sleep items. For example, the incident rate ratios for waking too early (95% CI) were 1.23 (1.10-1.38) for the women in the 1-month suspension group and 1.30 (1.17-1.45) for the 2-month suspension group, compared with women who continued the use of hormone therapy. Age and type of and duration of hormone therapy use did not modify these relationships.Short-term hormone therapy suspension was related to moderately greater frequency of sleep problems. Alternative forms of sleep management may benefit women who choose to discontinue hormone therapy use.
| S-EPMC3203993 | biostudies-literature
Project description:Bifidobacterium and Lactobacillus Probiotics and Gut Dysbiosis in Preterm Infants: The PRIMAL Randomized Clinical Trial
| PRJEB85138 | ENA
Project description:Bifidobacterium and Lactobacillus Probiotics and Gut Dysbiosis in Preterm Infants: The PRIMAL Randomized Clinical Trial
| PRJEB85277 | ENA
Project description:AimsThe transthyretin (TTR) stabilizer, tafamidis, has demonstrated efficacy and safety in the treatment of TTR familial amyloid polyneuropathy (20 mg day(-1) ). Tafamidis use in TTR cardiomyopathy led to the study of the potential effect of tafamidis on the QTc interval in healthy subjects.MethodsThis randomized, three treatment, three period, six sequence crossover study with placebo, a positive control (moxifloxacin 400 mg) and tafamidis (400 mg, to achieve a supra-therapeutic Cmax of ~20 µg ml(-1) ) was conducted in healthy volunteers at three clinical research units. Oral dosing in each of the three treatment periods was separated by a washout period of ≥ 14 days. Serial triplicate 12-lead electrocardiograms were performed. QTc intervals were derived using the Fridericia correction method. Safety and tolerability were assessed by physical examination, vital signs measurement, laboratory analyses and monitoring of adverse events (AEs).ResultsA total of 42 subjects completed the study. The upper limit of the two-sided 90% confidence intervals (CIs) for the difference in baseline-adjusted QTc F between tafamidis 400 mg and placebo was <10 ms (non-inferiority criterion) for all time points. The lower limit of the two-sided 90% CI between moxifloxacin 400 mg and placebo exceeded 5 ms at the pre-specified moxifloxacin tmax of 3 h post-dose, confirming assay sensitivity. Cmax and AUC(0,24 h) for tafamidis were 20.36 µg ml(-1) and 305.4 µg ml(-1) h, respectively. There were no serious/severe AEs or treatment discontinuations due to AEs.ConclusionsThis thorough QTc study suggests that a supra-therapeutic single 400 mg oral dose of tafamidis does not prolong the QTc interval and is well-tolerated in healthy volunteers.
| S-EPMC4456124 | biostudies-literature
Project description:Umibecestat, an orally active β-secretase inhibitor, reduces the production of amyloid beta-peptide that accumulates in the brain of patients with Alzheimer's disease. The echocardiogram effects of umibecestat, on QTcF (Fridericia-corrected QT), on PR and QRS and heart rate (HR), were estimated by concentration-effect modeling. Three phase I/II studies with durations up to 3 months, with 372 healthy subjects over a wide age range, including both sexes and 2 ethnicities, were pooled, providing a large data set with good statistical power. No clinically relevant effect on QTcF, PR interval, QRS duration, or HR were observed up to supratherapeutic doses. The upper bound of 90% confidence intervals of the ∆QTcF was below the 10 ms threshold of regulatory concern for all concentrations measured. Prespecified sensitivity analysis confirmed the results in both sexes, in those over and below 60 years, and in Japanese subjects. All conclusions were endorsed by the US Food and Drug Administration (FDA).
| S-EPMC7719381 | biostudies-literature
Project description:ImportancePatients with atrial fibrillation (AF) experience poor functional capacity and quality of life (QOL). High-intensity interval training (HIIT) has been shown to elicit greater improvements in functional capacity and QOL compared with moderate to vigorous intensity continuous training (MICT) in other cardiovascular populations, yet HIIT remains understudied in AF.ObjectiveTo compare the effects of 12 weeks of HIIT and MICT-based cardiovascular rehabilitation (CR) on functional capacity and general QOL in patients with persistent and permanent AF. Disease-specific QOL, resting heart rate (HR), time in AF, and physical activity (PA) levels were also assessed.Design, setting, and participantsThis randomized clinical trial, conducted between November 17, 2015, and February 4, 2020, at a tertiary-care cardiovascular health center in Ottawa, Canada, recruited 94 patients with persistent and permanent AF.InterventionsHigh-intensity interval training (23 minutes: two 8-minute interval training blocks of 30-second work periods at 80%-100% of peak power output interspersed with 30-second recovery) or CR (60 minutes: continuous aerobic conditioning within 67%-95% of peak HR and 12-16 of 20 ratings of perceived exertion) twice weekly for 12 weeks.Main outcomes and measuresThe primary outcomes were changes in functional capacity (6-minute walk test [6MWT] distance) and general QOL (Short Form 36) from baseline to 12 weeks' follow-up. Secondary outcomes included changes in disease-specific QOL (Atrial Fibrillation Severity Scale), resting HR, time in AF, and PA levels. An intention-to-treat analysis was used to compare changes between groups.ResultsOf the 94 patients who consented, 86 participated (mean [SD] age, 69 [7] years; 57 [66.3%] men). No significant differences in improvements in 6MWT distance (mean [SD], 21.3 [34.1] vs 13.2 [55.2] m; P = .42) and general QOL (Physical Component Summary, 0.5 [6.1] vs 1.1 [4.9] points; P = .87) between HIIT and CR were observed. No significant differences in improvements in disease-specific QOL (AF symptoms: -1.7 [4.3] vs -1.5 [4] points, P = .59), resting HR (-3.6 [10.6] vs -2.9 [12.4] beats per minute, P = .63), and moderate to vigorous PA levels (37.3 [93.4] vs 14.4 [125.7] min/wk; P = .35) between HIIT and CR were detected. Participants attended a mean (SD) of 18.3 (6.1) (75.1%) HIIT sessions and 20.0 (4.5) (83.4%) CR sessions (P = .36).Conclusions and relevanceIn this randomized clinical trial, twice-weekly 23-minute HIIT was as efficacious as twice-weekly 60-minute CR in improving functional capacity, general and disease-specific QOL, resting HR, and PA levels in patients with persistent and permanent AF.Trial registrationClinicalTrials.gov Identifier: NCT02602457.
| S-EPMC9623436 | biostudies-literature