Back to results

Thrombolysis in Myocardial Infarction (TIMI)

Primary Purpose

Cardiovascular Diseases, Coronary Disease, Heart Diseases

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

tissue plasminogen activator

angioplasty, transluminal, percutaneous coronary

About this trial

This is an interventional treatment trial for Cardiovascular Diseases

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Men and women under age 76. Patients had acute myocardial infarction.

Sites / Locations

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

NCT ID

NCT00000505

First Posted

October 27, 1999

Last Updated

March 15, 2016

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT00000505

Brief Title

Thrombolysis in Myocardial Infarction (TIMI)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2000

Overall Recruitment Status

Completed

Study Start Date

April 1983 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

December 1990 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

5. Study Description

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 500,000 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, and/or 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 1.5 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 3,534 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 1,681 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 60.5 percent of the 1,500 patients who underwent catheterization in the invasive strategy group. The remaining 39.5 percent or 593 patients did not have angioplasty performed. There were 1,658 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 13.5 percent of patients in this arm underwent coronary angioplasty, 7.6 percent underwent bypass surgery, and 1.1 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiovascular Diseases, Coronary Disease, Heart Diseases, Myocardial Infarction, Myocardial Ischemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Allocation

Randomized

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

tissue plasminogen activator

Intervention Type

Procedure

Intervention Name(s)

angioplasty, transluminal, percutaneous coronary

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Men and women under age 76. Patients had acute myocardial infarction.

Overall Study Officials: