Ignite Creation Date:
2024-05-05 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000505
Status:
COMPLETED
Last Update Posted:
2016-03-16
First Post:
1999-10-27
Brief Title:
Thrombolysis in Myocardial Infarction TIMI
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:
In TIMI I to assess the relative thrombolytic activity and side effects of intravenous recombinant tissue-type plasminogen activator rt-PA versus intravenous streptokinase in patients with acute myocardial infarction In TIMI II to assess whether intravenous rt-PA given in the early hours of acute myocardial infarction should be followed by percutaneous transluminal coronary angioplasty PTCA
Detailed Description:
BACKGROUND
Coronary artery disease is the leading cause of death in the United States accounting for almost 500000 deaths each year Studies have confirmed that myocardial infarction is related to an occlusive coronary thrombus in up to 80 percent of patients First and second-generation thrombolytic agents including streptokinase and rt-PA have been successfully used to restore myocardial blood flow where thrombus has occluded an infarct-related coronary artery However further clinical investigation was necessary to determine the most suitable thrombolytic agent dose and method of administration the risk of subsequent reocclusion restenosis andor myocardial infarction the need for additional therapies and the likelihood of benefit or hemorrhagic complications
In 1983 the National Heart Lung and Blood Institute established the TIMI Study Group The group consisted of 13 clinical centers later expanded to 24 a Radiographic Core Laboratory Radionuclide Core Laboratory and a Data Coordinating Center
DESIGN NARRATIVE
The TIMI trial was conducted in two stages In Phase I or TIMI I eligible patients were randomized to receive either 80 mg of recombinant tissue-type plasminogen activator rt-PA or 15 million units of streptokinase intravenously to determine relative safety and efficacy Following randomization patients found to have angiographically documented stenosis greater than 50 percent in the infarct-related artery received thrombolytic therapy in a double-blind fashion full anticoagulation and conventional care Patients subsequently underwent repeat catheterization radionuclide ventriculogram and pre-discharge six-week and six-month cardiovascular examination
TIMI I was stopped in February 1985 because of statistically significant differences in coronary reperfusion rates in the treatment groups rt-PA was found to be the superior thrombolytic agent Following TIMI Phase I the manufacturer of rt-PA changed to a large-scale production method for rt-PA and the new product was found to have thrombolytic activity and specificity in vitro and in experimental animals comparable to the product manufactured by the old method However the TIMI investigators concluded that clinical evaluation would be necessary prior to initiation of TIMI Phase II
Thus TIMI Open Label Phase studies were initiated in 1985 with the aim of establishing the safety and efficacy of the new intravenous rt-PA As in Phase I the endpoint was lysis of coronary thrombus within 90 minutes of the initiation of treatment in patients with documented total occlusion of the infarct-related coronary artery Additional goals of the study were to determine reocclusion rates of infarct-related arteries at 18-48 hours as well as to determine the efficacy of PTCA to maintain perfusion in infarct-related arteries and prevention of recurrent myocardial infarction The TIMI Open Label Phase studies determined that optimal coronary recanalization and maintenance of reperfusion occurred with 150 mg of new rt-PA infused over six hours However subsequent hemorrhagic complications observed with 150 mg rt-PA necessitated a change in the dose of rt-PA to 100 mg
In TIMI II patient entry began in April 1986 and ended in June 1988 with enrollment of 3534 patients Patients were treated with intravenous rt-PA within four hours of the onset of chest pain thought to be caused by myocardial infarction and randomly assigned to an invasive strategy or a conservative strategy The primary endpoint was survival free of recurrent myocardial infarction at six weeks and one year of follow-up There were 1681 patients assigned to the delayed invasive strategy in which catheterization was performed between 18 and 48 hours after rt-PA therapy If catheterization showed a greater than 60 percent subtotal stenosis of the infarct-related artery that was considered to be technically approachable angioplasty was attempted Angioplasty was performed in 605 percent of the 1500 patients who underwent catheterization in the invasive strategy group The remaining 395 percent or 593 patients did not have angioplasty performed There were 1658 patients assigned to a conservative strategy in which cardiac catheterization was reserved for the 587 patients who had spontaneous or exercise-induced myocardial ischemia within 21 days of infarction A total of 135 percent of patients in this arm underwent coronary angioplasty 76 percent underwent bypass surgery and 11 percent underwent both procedures 77 percent of the patients in the conservative strategy group had no revascularization procedure within 21 days of infarction
TIMI IIA a subtrial of 586 patients investigated whether immediate cardiac catheterization with percutaneous transluminal coronary angioplasty when appropriate would confer an advantage over the same procedure performed 18 to 48 hours later All patients were treated with intravenous rt-PA within four hours of the onset of acute myocardial infarction
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
Coronary artery disease is the leading cause of death in the United States accounting for almost 500000 deaths each year Studies have confirmed that myocardial infarction is related to an occlusive coronary thrombus in up to 80 percent of patients First and second-generation thrombolytic agents including streptokinase and rt-PA have been successfully used to restore myocardial blood flow where thrombus has occluded an infarct-related coronary artery However further clinical investigation was necessary to determine the most suitable thrombolytic agent dose and method of administration the risk of subsequent reocclusion restenosis andor myocardial infarction the need for additional therapies and the likelihood of benefit or hemorrhagic complications
In 1983 the National Heart Lung and Blood Institute established the TIMI Study Group The group consisted of 13 clinical centers later expanded to 24 a Radiographic Core Laboratory Radionuclide Core Laboratory and a Data Coordinating Center
DESIGN NARRATIVE
The TIMI trial was conducted in two stages In Phase I or TIMI I eligible patients were randomized to receive either 80 mg of recombinant tissue-type plasminogen activator rt-PA or 15 million units of streptokinase intravenously to determine relative safety and efficacy Following randomization patients found to have angiographically documented stenosis greater than 50 percent in the infarct-related artery received thrombolytic therapy in a double-blind fashion full anticoagulation and conventional care Patients subsequently underwent repeat catheterization radionuclide ventriculogram and pre-discharge six-week and six-month cardiovascular examination
TIMI I was stopped in February 1985 because of statistically significant differences in coronary reperfusion rates in the treatment groups rt-PA was found to be the superior thrombolytic agent Following TIMI Phase I the manufacturer of rt-PA changed to a large-scale production method for rt-PA and the new product was found to have thrombolytic activity and specificity in vitro and in experimental animals comparable to the product manufactured by the old method However the TIMI investigators concluded that clinical evaluation would be necessary prior to initiation of TIMI Phase II
Thus TIMI Open Label Phase studies were initiated in 1985 with the aim of establishing the safety and efficacy of the new intravenous rt-PA As in Phase I the endpoint was lysis of coronary thrombus within 90 minutes of the initiation of treatment in patients with documented total occlusion of the infarct-related coronary artery Additional goals of the study were to determine reocclusion rates of infarct-related arteries at 18-48 hours as well as to determine the efficacy of PTCA to maintain perfusion in infarct-related arteries and prevention of recurrent myocardial infarction The TIMI Open Label Phase studies determined that optimal coronary recanalization and maintenance of reperfusion occurred with 150 mg of new rt-PA infused over six hours However subsequent hemorrhagic complications observed with 150 mg rt-PA necessitated a change in the dose of rt-PA to 100 mg
In TIMI II patient entry began in April 1986 and ended in June 1988 with enrollment of 3534 patients Patients were treated with intravenous rt-PA within four hours of the onset of chest pain thought to be caused by myocardial infarction and randomly assigned to an invasive strategy or a conservative strategy The primary endpoint was survival free of recurrent myocardial infarction at six weeks and one year of follow-up There were 1681 patients assigned to the delayed invasive strategy in which catheterization was performed between 18 and 48 hours after rt-PA therapy If catheterization showed a greater than 60 percent subtotal stenosis of the infarct-related artery that was considered to be technically approachable angioplasty was attempted Angioplasty was performed in 605 percent of the 1500 patients who underwent catheterization in the invasive strategy group The remaining 395 percent or 593 patients did not have angioplasty performed There were 1658 patients assigned to a conservative strategy in which cardiac catheterization was reserved for the 587 patients who had spontaneous or exercise-induced myocardial ischemia within 21 days of infarction A total of 135 percent of patients in this arm underwent coronary angioplasty 76 percent underwent bypass surgery and 11 percent underwent both procedures 77 percent of the patients in the conservative strategy group had no revascularization procedure within 21 days of infarction
TIMI IIA a subtrial of 586 patients investigated whether immediate cardiac catheterization with percutaneous transluminal coronary angioplasty when appropriate would confer an advantage over the same procedure performed 18 to 48 hours later All patients were treated with intravenous rt-PA within four hours of the onset of acute myocardial infarction
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 |
|---|---|---|---|
| R01HL042311 | NIH | None | httpsreporternihgovquickSearchR01HL042311 |