Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000472
Status:
COMPLETED
Last Update Posted:
2016-03-16
First Post:
1999-10-27
Brief Title:
Thrombolysis in Myocardial Ischemia Trial TIMI III
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:
2000-07
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:
The Thrombolysis in Myocardial Ischemia Trial TIMI III focused on unstable angina and non-Q-wave myocardial infarction The trial was designed to determine by coronary arteriography the incidence of coronary thrombi in these conditions and the response of these thrombi to tissue-type plasminogen activator t-PA in TIMI IIIA and the effects of thrombolytic therapy and of an early invasive strategy on clinical outcome in TIMI IIIB There was also a registry with two components A roster enumerated all patients with unstable angina or non-Q-wave myocardial infarction enrolled at cooperating hospitals From the roster a study population of 1893 subjects was selected and followed prospectively for the year to determine incidence of death or myocardial infarction
Detailed Description:
BACKGROUND
TIMI IIIA and TIMI IIIB follow the contract-supported clinical trial Thrombolysis in Myocardial Infarction TIMI I TIMI IIA and TIMI II
Myocardial ischemic syndromes account for a large portion of the annual mortality and morbidity from all causes in industrialized countries and encompass a wide clinical-pathologic spectrum At one end of this spectrum are patients with chronic stable angina When studied by coronary arteriography such patients usually have obstructive atherosclerotic disease with no evidence of fresh thrombosis At the other end of the spectrum are patients with acute myocardial infarction who present with a discrete episode of prolonged chest pain accompanied by persistent ST-segment elevation Such patients have a high incidence of thrombotic coronary artery occlusion and the early intravenous administration of thrombolytic agents has been shown to re-establish perfusion limit the extent of left ventricular dysfunction and reduce both early or in-hospital and late or one year mortality in this group
Patients with non-Q-wave myocardial infarction and unstable angina fall between these two extremes In the days and weeks following the onset of their disorder their prognosis for survival is better than that of patients with Q-wave myocardial infarction but worse than that of patients with stable angina Some patients with unstable angina progress to acute myocardial infarction and some of those with non-Q-wave infarction experience an unstable course with reinfarction Although others recover from the acute episode without subsequent infarction or reinfarction they frequently have severe obstructive coronary artery disease and may be left with severe chronic stable angina National summaries of hospital records indicate that 750000 patients are hospitalized yearly with unstable angina and 250000 with non-Q-wave myocardial infarction
Once the results of creatine kinase measurements and serial electrocardiograms are available the identification of patients experiencing non-Q-wave myocardial infarction is relatively simple Identification of patients experiencing unstable angina is more difficult since numerous definitions of the condition have been offered There is agreement however on two important features of unstable angina First ischemia usually develops at rest or is precipitated by minimal exertion this differs from chronic stable angina in which most ischemic episodes are precipitated by physical exertion or strong emotion and the resultant increase in myocardial oxygen demand Second ischemia is often associated with transient ST-segment depression or elevation in contrast to the persistent ST-segment elevation characteristic of patients who develop Q-wave infarction
It has been observed in small numbers of patients that unlike patients with chronic stable ischemia patients with unstable angina or non-Q-wave myocardial infarction frequently have a thrombus in a major coronary artery Initial conventional therapy for unstable angina consists of bed rest oxygen nitrates beta-blockers calcium antagonists and aspirin The use of heparin is widespread but controversial In many tertiary care hospitals angiography followed by PTCA is frequently performed whereas in community hospitals patients are often managed without angiography
Prior to the TIMI III trial patients with non-Q-wave myocardial infarction were usually treated in the same way patients with Q-wave myocardial infarction were treated prior to the advent of thrombolytic therapy Neither heparin therapy nor thrombolytic therapy was routinely employed although knowledge of the role of thrombosis in some patients with this condition had raised the possibility that one or both approaches might be helpful Although the early prognosis was favorable awareness that the longer-term prognosis was as serious as that following Q-wave myocardial infarction had led to increasing use of follow-up coronary angiography to identify patients for whom PTCA or CABG might be useful Whether or not revascularization improved prognosis in these patients had not been established
Previous studies of thrombolytic therapy for unstable angina and non-Q-wave myocardial infarction were limited in number and size The results suggested a benefit but the significance of this benefit and its relation to the risks and costs of therapy remained to be answered Also the value of routine early coronary angiography followed by PTCA andor CABG was still unclear in both these conditions
DESIGN NARRATIVE
The two clinical trials were initiated simultaneously in different groups of TIMI III clinical centers All patients enrolled in the study received standard coronary care unit care including bed rest and oxygen In TIMI IIIA patients received baseline angiograms and were randomized in a double-blind manner to t-PA or placebo All patients then received intravenous heparin The primary endpoint was the number of patients with a successful result of therapy defined as an improvement in TIMI perfusion by two grades from 0 to 2 or 3 or from 1 to 3 or a ten percent reduction in the severity of stenosis The reduction was based on a comparison between the baseline angiogram and the follow-up angiogram obtained 18 to 48 hours later Patients in TIMI IIIA were enrolled over a nine month period The total duration was 24 months including 12 months of data analysis
In TIMI IIIB a total of 1473 patients seen within 24 hours of ischemic chest pain at rest considered to represent unstable angina or non-Q-wave myocardial infarction NQMI were randomized using a 2 x 2 factorial design to compare t-PA versus placebo as initial therapy and an early invasive strategy consisting of early coronary arteriography followed by revascularization when the anatomy was suitable versus an early conservative strategy consisting of coronary arteriography followed by revascularization if initial medical therapy failed All patients were treated with bed rest anti-ischemic medications aspirin and heparin The primary endpoint for the t-PA placebo comparison was death myocardial infarction or failure of initial therapy at six weeks Randomization began in October 1989 and concluded in June 1992 The primary endpoint for the early invasive and early conservative strategies was death post randomization myocardial infarction or an unsatisfactory exercise tolerance test ETT at six weeks
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
TIMI IIIA and TIMI IIIB follow the contract-supported clinical trial Thrombolysis in Myocardial Infarction TIMI I TIMI IIA and TIMI II
Myocardial ischemic syndromes account for a large portion of the annual mortality and morbidity from all causes in industrialized countries and encompass a wide clinical-pathologic spectrum At one end of this spectrum are patients with chronic stable angina When studied by coronary arteriography such patients usually have obstructive atherosclerotic disease with no evidence of fresh thrombosis At the other end of the spectrum are patients with acute myocardial infarction who present with a discrete episode of prolonged chest pain accompanied by persistent ST-segment elevation Such patients have a high incidence of thrombotic coronary artery occlusion and the early intravenous administration of thrombolytic agents has been shown to re-establish perfusion limit the extent of left ventricular dysfunction and reduce both early or in-hospital and late or one year mortality in this group
Patients with non-Q-wave myocardial infarction and unstable angina fall between these two extremes In the days and weeks following the onset of their disorder their prognosis for survival is better than that of patients with Q-wave myocardial infarction but worse than that of patients with stable angina Some patients with unstable angina progress to acute myocardial infarction and some of those with non-Q-wave infarction experience an unstable course with reinfarction Although others recover from the acute episode without subsequent infarction or reinfarction they frequently have severe obstructive coronary artery disease and may be left with severe chronic stable angina National summaries of hospital records indicate that 750000 patients are hospitalized yearly with unstable angina and 250000 with non-Q-wave myocardial infarction
Once the results of creatine kinase measurements and serial electrocardiograms are available the identification of patients experiencing non-Q-wave myocardial infarction is relatively simple Identification of patients experiencing unstable angina is more difficult since numerous definitions of the condition have been offered There is agreement however on two important features of unstable angina First ischemia usually develops at rest or is precipitated by minimal exertion this differs from chronic stable angina in which most ischemic episodes are precipitated by physical exertion or strong emotion and the resultant increase in myocardial oxygen demand Second ischemia is often associated with transient ST-segment depression or elevation in contrast to the persistent ST-segment elevation characteristic of patients who develop Q-wave infarction
It has been observed in small numbers of patients that unlike patients with chronic stable ischemia patients with unstable angina or non-Q-wave myocardial infarction frequently have a thrombus in a major coronary artery Initial conventional therapy for unstable angina consists of bed rest oxygen nitrates beta-blockers calcium antagonists and aspirin The use of heparin is widespread but controversial In many tertiary care hospitals angiography followed by PTCA is frequently performed whereas in community hospitals patients are often managed without angiography
Prior to the TIMI III trial patients with non-Q-wave myocardial infarction were usually treated in the same way patients with Q-wave myocardial infarction were treated prior to the advent of thrombolytic therapy Neither heparin therapy nor thrombolytic therapy was routinely employed although knowledge of the role of thrombosis in some patients with this condition had raised the possibility that one or both approaches might be helpful Although the early prognosis was favorable awareness that the longer-term prognosis was as serious as that following Q-wave myocardial infarction had led to increasing use of follow-up coronary angiography to identify patients for whom PTCA or CABG might be useful Whether or not revascularization improved prognosis in these patients had not been established
Previous studies of thrombolytic therapy for unstable angina and non-Q-wave myocardial infarction were limited in number and size The results suggested a benefit but the significance of this benefit and its relation to the risks and costs of therapy remained to be answered Also the value of routine early coronary angiography followed by PTCA andor CABG was still unclear in both these conditions
DESIGN NARRATIVE
The two clinical trials were initiated simultaneously in different groups of TIMI III clinical centers All patients enrolled in the study received standard coronary care unit care including bed rest and oxygen In TIMI IIIA patients received baseline angiograms and were randomized in a double-blind manner to t-PA or placebo All patients then received intravenous heparin The primary endpoint was the number of patients with a successful result of therapy defined as an improvement in TIMI perfusion by two grades from 0 to 2 or 3 or from 1 to 3 or a ten percent reduction in the severity of stenosis The reduction was based on a comparison between the baseline angiogram and the follow-up angiogram obtained 18 to 48 hours later Patients in TIMI IIIA were enrolled over a nine month period The total duration was 24 months including 12 months of data analysis
In TIMI IIIB a total of 1473 patients seen within 24 hours of ischemic chest pain at rest considered to represent unstable angina or non-Q-wave myocardial infarction NQMI were randomized using a 2 x 2 factorial design to compare t-PA versus placebo as initial therapy and an early invasive strategy consisting of early coronary arteriography followed by revascularization when the anatomy was suitable versus an early conservative strategy consisting of coronary arteriography followed by revascularization if initial medical therapy failed All patients were treated with bed rest anti-ischemic medications aspirin and heparin The primary endpoint for the t-PA placebo comparison was death myocardial infarction or failure of initial therapy at six weeks Randomization began in October 1989 and concluded in June 1992 The primary endpoint for the early invasive and early conservative strategies was death post randomization myocardial infarction or an unsatisfactory exercise tolerance test ETT at six weeks
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 |
|---|---|---|---|
| R01HL042428 | NIH | None | httpsreporternihgovquickSearchR01HL042428 |