Ignite Creation Date:
2024-05-05 @ 10:05 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00005243
Status:
COMPLETED
Last Update Posted:
2016-03-16
First Post:
2000-05-25
Brief Title:
Triggers of Ventricular Arrhythmias TOVA Study
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2005-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To investigate factors which trigger the discharge of implantable cardioverter-defibrillators ICDs
Detailed Description:
BACKGROUND
The classic studies of daily activity prior to myocardial infarction onset conducted by Master in the 1960s failed to show a consistent relationship between any particular activity and disease onset However they were conducted at a time when less was known of the pathophysiology of myocardial infarction when there was less understanding of the effect of daily activities on physiologic processes likely to lead to myocardial infarction onset and when epidemiologic methods were less well developed than at present Certain activities now of considerable interest such as wake time time of assuming the upright posture eating and taking of medications were not examined and those that were examined such as walking and heavy exertion were evaluated without reference to control exposure In addition modern enzymatic methods of confirmation of the diagnosis of acute myocardial infarction were not utilized Despite these deficiencies the studies of Master provide the foundation for the hypothesis that the onset of myocardial infarction is almost always a random event
Observations of morning increase in the incidence of myocardial infarction sudden cardiac death and myocardial ischemia demonstrate that the timing of these events is not wholly random The most extensive data on the time of onset of the pain of myocardial infarction were published in 1976 by the World Health Organization in the report of the Myocardial Infarction Community Registers from 19 European centers Data from over 8900 patients clearly demonstrated a peak incidence of onset of pain from 8 to 11 am Data from the Multicenter Investigation of the Limitation of Infarct Size MILIS Study revealed a significant circadian variation with an increased incidence of myocardial infarction in the period from 6 am to noon The morning increase was detected despite the fact that data concerning the time of awakening and prior medication usage were lacking in this patient population This finding has been confirmed by Willich in a study of over 1700 patients with infarct onset determined by creatine kinase timing The patients showed a four-fold increased morning onset of myocardial infarction relative to occurrence at night When the relationship of infarction onset to time of awakening is clarified and possible precipitants evaluated increased information about triggering processes will be available Such information will assist in the design of preventive therapy which can be evaluated in randomized trials
The Determinants Study began in 1989 shortly after widespread acceptance of the circadian variation in Ml occurrence The study was initiated to utilize state-of-the art epidemiologic techniques to determine the role of daily activities in the triggering of Ml The investigators created a new epidemiologic technique the case-crossover method developed and tested a 24-page interview form established a large study group of hospitals with trained interviewers instituted quality control measures and enrolled over 2000 subjects
The Triggers of Ventricular Arrhythmias TOVA Study began in FY 1999 under the same grant number as the Modifiers and Determinants Studies The TOVA study investigates factors associated with triggering of discharge of implantable cardioverter-defibrillators ICDs
DESIGN NARRATIVE
The Myocardial Infarction Onset Study Determinants Study supported from 1989 to 1993 had a case-control design Coronary care units in the Boston and Worcester Massachusetts areas collaborated Eligible patients were interviewed concerning whether the myocardial infarction was the first or not and the nature and timing of pain the time of waking the day of onset of the infarction and the time of assuming upright posture the number of times the patient awoke from sleep and assumed the upright posture during the night or day prior to myocardial infarction whether the patient was receiving therapy with a beta-blocker or aspirin and at what time the medication was taken in the 24 hours preceding the myocardial infarction and age and smoking status A questionnaire was administered on educational background marital status occupation usual activity in recent past and specifically on the day before onset including diet coffee consumption smoking and exercise sleep habits geographic location where the infarct occurred Data were also abstracted from the medical record Patient enrollment ended in the fourth year Relative risks associated with hypothesized risk factors for onset of myocardial infarction were estimated by comparing observed exposure frequencies immediately prior to myocardial infarction with expected values derived from exposure frequencies in the same patients at other times of the day and in other patients at the same time of day
The grant was renewed in 1994 through November 1998 to conduct a new study entitled Modifiers of Myocardial Infarction Onset Modifiers Study The Modifiers Study elucidated the pathophysiology of acute myocardial infarction Ml onset and utilized the methodologic techniques 50-hospital national study group and findings of the completed NHLBl-funded Determinants of Myocardial Infarction Onset Study Determinants Study The Modifiers Study identified factors that increased or decreased the susceptibility of patients to the triggers of acute Ml previously identified
It was hoped that the Modifiers Study would answer the major questions raised by the results of the Determinants Study It tested hypotheses concerning five groups of factors that were potential modifiers of susceptibility to the triggering of acute MI l Pharmacologic means of Prevention - that beta blockers aspirin angiotensin converting enzyme inhibitors and estrogen use decrease susceptibility to triggers 2 Timing - that susceptibility does not increase in the morning but does in the winter and that exogenous rather than endogenous daily rhythms determine onset 3 Traditional chronic risk factors - that diabetes hypertension and smoking increase susceptibility and that regular exercise decreases susceptibility to triggers other than exertion 4 Gender - that women are less susceptible to triggering and 5 Dietary factors - that chronic moderate alcohol use and anti-oxidants decrease susceptibility To test the hypotheses 5700 interviews were needed By the completion of the Determinants Study in March 1993 over 2000 interviews were completed It was estimated that continuation in the Modifiers Study of the 77 interviews per month would provide the required 3700 additional interviews by December 1997
TOVA was begun in FY 1999 to identify activities such as heavy exertion that trigger ICD discharge assess factors such as beta-blockade that modify the susceptibility to triggering determine if ICD discharges occurred more frequently in certain periods ie the 3 hours after awakening on Monday and in winter and utilize electrograms recorded prior to ICD discharge to identify sympathetic activation during triggering TOVA used a cohort design with a nested case-crossover analysis TOVA characterized triggering in episodes of ICD discharge in 1140 patients treated in 31 centers nationwide over four years
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
The classic studies of daily activity prior to myocardial infarction onset conducted by Master in the 1960s failed to show a consistent relationship between any particular activity and disease onset However they were conducted at a time when less was known of the pathophysiology of myocardial infarction when there was less understanding of the effect of daily activities on physiologic processes likely to lead to myocardial infarction onset and when epidemiologic methods were less well developed than at present Certain activities now of considerable interest such as wake time time of assuming the upright posture eating and taking of medications were not examined and those that were examined such as walking and heavy exertion were evaluated without reference to control exposure In addition modern enzymatic methods of confirmation of the diagnosis of acute myocardial infarction were not utilized Despite these deficiencies the studies of Master provide the foundation for the hypothesis that the onset of myocardial infarction is almost always a random event
Observations of morning increase in the incidence of myocardial infarction sudden cardiac death and myocardial ischemia demonstrate that the timing of these events is not wholly random The most extensive data on the time of onset of the pain of myocardial infarction were published in 1976 by the World Health Organization in the report of the Myocardial Infarction Community Registers from 19 European centers Data from over 8900 patients clearly demonstrated a peak incidence of onset of pain from 8 to 11 am Data from the Multicenter Investigation of the Limitation of Infarct Size MILIS Study revealed a significant circadian variation with an increased incidence of myocardial infarction in the period from 6 am to noon The morning increase was detected despite the fact that data concerning the time of awakening and prior medication usage were lacking in this patient population This finding has been confirmed by Willich in a study of over 1700 patients with infarct onset determined by creatine kinase timing The patients showed a four-fold increased morning onset of myocardial infarction relative to occurrence at night When the relationship of infarction onset to time of awakening is clarified and possible precipitants evaluated increased information about triggering processes will be available Such information will assist in the design of preventive therapy which can be evaluated in randomized trials
The Determinants Study began in 1989 shortly after widespread acceptance of the circadian variation in Ml occurrence The study was initiated to utilize state-of-the art epidemiologic techniques to determine the role of daily activities in the triggering of Ml The investigators created a new epidemiologic technique the case-crossover method developed and tested a 24-page interview form established a large study group of hospitals with trained interviewers instituted quality control measures and enrolled over 2000 subjects
The Triggers of Ventricular Arrhythmias TOVA Study began in FY 1999 under the same grant number as the Modifiers and Determinants Studies The TOVA study investigates factors associated with triggering of discharge of implantable cardioverter-defibrillators ICDs
DESIGN NARRATIVE
The Myocardial Infarction Onset Study Determinants Study supported from 1989 to 1993 had a case-control design Coronary care units in the Boston and Worcester Massachusetts areas collaborated Eligible patients were interviewed concerning whether the myocardial infarction was the first or not and the nature and timing of pain the time of waking the day of onset of the infarction and the time of assuming upright posture the number of times the patient awoke from sleep and assumed the upright posture during the night or day prior to myocardial infarction whether the patient was receiving therapy with a beta-blocker or aspirin and at what time the medication was taken in the 24 hours preceding the myocardial infarction and age and smoking status A questionnaire was administered on educational background marital status occupation usual activity in recent past and specifically on the day before onset including diet coffee consumption smoking and exercise sleep habits geographic location where the infarct occurred Data were also abstracted from the medical record Patient enrollment ended in the fourth year Relative risks associated with hypothesized risk factors for onset of myocardial infarction were estimated by comparing observed exposure frequencies immediately prior to myocardial infarction with expected values derived from exposure frequencies in the same patients at other times of the day and in other patients at the same time of day
The grant was renewed in 1994 through November 1998 to conduct a new study entitled Modifiers of Myocardial Infarction Onset Modifiers Study The Modifiers Study elucidated the pathophysiology of acute myocardial infarction Ml onset and utilized the methodologic techniques 50-hospital national study group and findings of the completed NHLBl-funded Determinants of Myocardial Infarction Onset Study Determinants Study The Modifiers Study identified factors that increased or decreased the susceptibility of patients to the triggers of acute Ml previously identified
It was hoped that the Modifiers Study would answer the major questions raised by the results of the Determinants Study It tested hypotheses concerning five groups of factors that were potential modifiers of susceptibility to the triggering of acute MI l Pharmacologic means of Prevention - that beta blockers aspirin angiotensin converting enzyme inhibitors and estrogen use decrease susceptibility to triggers 2 Timing - that susceptibility does not increase in the morning but does in the winter and that exogenous rather than endogenous daily rhythms determine onset 3 Traditional chronic risk factors - that diabetes hypertension and smoking increase susceptibility and that regular exercise decreases susceptibility to triggers other than exertion 4 Gender - that women are less susceptible to triggering and 5 Dietary factors - that chronic moderate alcohol use and anti-oxidants decrease susceptibility To test the hypotheses 5700 interviews were needed By the completion of the Determinants Study in March 1993 over 2000 interviews were completed It was estimated that continuation in the Modifiers Study of the 77 interviews per month would provide the required 3700 additional interviews by December 1997
TOVA was begun in FY 1999 to identify activities such as heavy exertion that trigger ICD discharge assess factors such as beta-blockade that modify the susceptibility to triggering determine if ICD discharges occurred more frequently in certain periods ie the 3 hours after awakening on Monday and in winter and utilize electrograms recorded prior to ICD discharge to identify sympathetic activation during triggering TOVA used a cohort design with a nested case-crossover analysis TOVA characterized triggering in episodes of ICD discharge in 1140 patients treated in 31 centers nationwide over four years
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL041016 | NIH | None | httpsreporternihgovquickSearchR01HL041016 |