T-TIME
Research type
Research Study
Full title
A randomised, double blind, placebo-controlled, parallel group, Trial of very low-dose and low-dose adjunctive Tenecteplase during prIMary PCI (T-TIME)
IRAS ID
103359
Contact name
Colin Berry
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde NHS R&D
Eudract number
2012-001123-13
Research summary
Heart attack is a leading cause of heart failure and death worldwide. A heart attack is usually caused by an acute coronary thrombosis which is best treated by emergency angioplasty with stenting to open the blocked artery and restore blood flow to the injured heart muscle. Even although angioplasty is usually successful, nearly one half of patients have persistently reduced heart muscle blood flow leading to permanent heart muscle injury. This problem is due to MICROVASCULAR OBSTRUCTION (MVO), which manifests clinically with problems such as heart failure acutely and in the longer term. The main cause of MVO is microvascular thrombosis (small blood clots) affecting the small arterioles and capillaries subtended by the initially blocked culprit coronary artery, and to our knowledge, our proposal is the only trial aimed at selectively reducing heart injury by locally breaking down clot within the small blood vessels of the heart. Although contrast-enhanced magnetic resonance imaging (MRI) can detect MVO, offering a useful independent predictor of adverse outcome, this knowledge is not exploited as there are no known validated treatments or strategies for the management of MVO. In this study, we propose to exploit the positive therapeutic effect of tenecteplase, a clot-breaking treatment for heart attacks. Full dose tenecteplase treats heart attacks very effectively; however it can in some cases cause life-threatening bleeding complications. Our strategy of using very low doses of tenecteplase to target blood clots in the small blood vessels of the heart bypasses this issue, but exploits the drug??s thrombolytic potential by using very low doses of tenecteplase to target the small blood clots which cause MVO. We will conduct a placebo-controlled trial of low (1/10th) or very low (1/100th) dose tenecteplase given directly into the coronary artery following catheter mediated restoration of coronary artery blood flow (standard care) in 180 patients (60/group). Following catheter based removal of the blood clot (standard care), the catheter will be flushed on the table and used to slowly infuse the study drug over ~10 min directly into the culprit artery. Our aim is to determine whether tenecteplase might prevent and/or attenuate MVO with proof of clinical efficacy being demonstrated through reduced MVO and improved heart blood flow. Clinical techniques will be used to evaluate the efficacy of the different dosages acutely (ECG pre and 60 min post-PCI, coronary pressure wire during PCI) and subsequently by perfusion MRI 2 days later. MRI at 6 months will be used to measure INFARCT SIZE (scar) and heart function/volumes with these parameters representing 'surrogate' measures of health outcome. Safety assessments will include follow-up for clinical events, including death and readmission to hospital (average follow-up 18 months). We have an ADAPTIVE TRIAL DESIGN and the size of the study will adjust according to the results. If our hypothesis proves correct then we will plan a large clinical trial.
REC name
West of Scotland REC 1
REC reference
12/WS/0109
Date of REC Opinion
18 Jul 2012
REC opinion
Further Information Favourable Opinion