A Trial of Low-dose Adjunctive alTeplase During prIMary PCI

NCT02257294 | Completed Phase 2 DMC

• 2 other identifiers: GN12CA45012/170/45
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to determine the safety and efficacy of reduced doses (10 mg and 20 mg) of intra-coronary alteplase compared with placebo as an adjunct to PCI in reducing MVO and its consequences in high risk patients with STEMI.

Conditions

Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• The amount of MVO (% of Left Ventricular (LV) mass) revealed by late (10 - 15 min) gadolinium contrast enhancement MRI 2 days post-MI.

  Amount of MVO (% of LV mass) revealed by late gadolinium contrast-enhanced MRI 10-15 minutes after contrast administration on an MRI scan performed 2-7 days post-MI.

  2-7 days

Secondary Outcomes (9)

• Angiogram

  0-2 hours

• ECG

  0-2 hours

• Haematology

  24 hours

• MRI

  2-7 days

• Safety

  2-7 days

Other Outcomes (11)

• Histopathology (sub-study)

  0 hours

• Angiogram

  0-2 hours

• Coronary Physiology (sub-study)

  0-2 hours

Study Arms (3)

Control Arm

PLACEBO COMPARATOR

two placebo vials

Other: Placebo

Arm A

ACTIVE COMPARATOR

Alteplase 10mg and placebo vial

Drug: Alteplase; Other: Placebo

Arm B

ACTIVE COMPARATOR

Alteplase 10mg and alteplase 10mg

Drug: Alteplase

Interventions

Alteplase DRUG

Single treatment consisting of a single slow infusion administration after reperfusion with aspiration thrombectomy ± angioplasty but before stenting during primary PCI.

Also known as: Actilyse

Arm A; Arm B

Placebo OTHER

Single treatment consisting of a single slow infusion administration after reperfusion with aspiration thrombectomy ± angioplasty but before stenting during primary PCI.

Arm A; Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males aged ≥ 18 years; females ≤ 18 years not of child bearing potential (defined as women who are post-menopausal or permanently sterilised (e.g. hysterectomy, tubal occlusion, bilateral salpingectomy)
• Acute myocardial infarction (symptoms onset ≤ 6 hours) with persistent ST-segment elevation or recent left bundle branch block
• Coronary artery occlusion (TIMI coronary flow grade 0 or 1) OR Impaired coronary flow (TIMI flow grade 2, slow but complete filling) in the presence of definite angiographic evidence of thrombus (TIMI grade 2+)
• Proximal-mid culprit lesion location in a major coronary artery (ie the right, left anterior descending, intermediate or circumflex coronary artery)
• Radial artery access

You may not qualify if:

• Shock (systolic blood pressure \<90 mmHg with clinical signs of peripheral hypoperfusion despite adequate filling)
• Normal coronary flow grade (TIMI flow grade 3) at initial angiography
• Functional coronary collateral supply (Rentrop grade 2/3) to culprit artery
• Multivessel PCI intended before the day 2-7 MRI Scan
• Non-cardiac co-morbidity with expected survival \<1 year
• Estimated body weight \<60kg
• Contra-indication to contrast-enhanced MRI
• Pacemaker
• Implantable defibrillator
• estimated Glomerular Filtration Rate (eGFR) \<30ml/min/1.73m²
• previous infarction in the culprit artery (known or suspected clinically, e.g. wall motion abnormality revealed by echocardiography)
• Significant bleeding problem either at present or within the past 6 months
• Patients with current concomitant oral anticoagulant therapy (INR \> 1.3), including apixaban, dabigatran and rivaroxaban
• Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial, or spinal surgery)
• Known Haemorrhagic diathesis

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (11)

Edinburgh Royal Infirmary

Edinburgh, United Kingdom

Location

Golden Jubilee National Hospital

Glasgow, G81 4HX, United Kingdom

Location

Leeds General Infirmary

Leeds, LS1 3EX, United Kingdom

Location

Glenfield Hospital

Leicester, United Kingdom

Location

Liverpool Heart and Chest Hospital

Liverpool, United Kingdom

Location

Barts Health Centre, St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

University Hospital of South Manchester NHS Foundation Trust

Manchester, M23 9LT, United Kingdom

Location

James Cook University Hospital

Middlesbrough, United Kingdom

Location

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6TD, United Kingdom

Location

Heart and Lung Centre, New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (8)

• Bulluck H, Carberry J, Carrick D, McCartney PJ, Maznyczka AM, Greenwood JP, Maredia N, Chowdhary S, Gershlick AH, Appleby C, Cotton JM, Wragg A, Curzen N, McEntegart M, Petrie MC, Eteiba H, Watkins S, Lindsay M, Mahrous A, Oldroyd KG, Berry C. A Noncontrast CMR Risk Score for Long-Term Risk Stratification in Reperfused ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Imaging. 2022 Mar;15(3):431-440. doi: 10.1016/j.jcmg.2021.08.006. Epub 2022 Jan 12.

  PMID: 35272808 DERIVED

• Maznyczka AM, McCartney PJ, Oldroyd KG, Lindsay M, McEntegart M, Eteiba H, Rocchiccioli JP, Good R, Shaukat A, Robertson K, Malkin CJ, Greenwood JP, Cotton JM, Hood S, Watkins S, Collison D, Gillespie L, Ford TJ, Weir RAP, McConnachie A, Berry C. Risk Stratification Guided by the Index of Microcirculatory Resistance and Left Ventricular End-Diastolic Pressure in Acute Myocardial Infarction. Circ Cardiovasc Interv. 2021 Feb;14(2):e009529. doi: 10.1161/CIRCINTERVENTIONS.120.009529. Epub 2021 Feb 16.

  PMID: 33591821 DERIVED

• Maznyczka AM, McCartney P, Duklas P, McEntegart M, Oldroyd KG, Greenwood JP, Muir D, Chowdhary S, Gershlick AH, Appleby C, Eteiba H, Cotton J, Wragg A, Curzen N, Tait RC, MacFarlane P, Welsh P, Sattar N, Petrie MC, Ford I, Fox KAA, McConnachie A, Berry C; T-TIME (Trial of low-dose adjunctive alTeplase during primary PCI) investigators. Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial. Heart. 2021 Jan 12:heartjnl-2020-317828. doi: 10.1136/heartjnl-2020-317828. Online ahead of print.

  PMID: 33436493 DERIVED

• Maznyczka AM, Oldroyd KG, Greenwood JP, McCartney PJ, Cotton J, Lindsay M, McEntegart M, Rocchiccioli JP, Good R, Robertson K, Eteiba H, Watkins S, Shaukat A, Petrie CJ, Murphy A, Petrie MC, Berry C. Comparative Significance of Invasive Measures of Microvascular Injury in Acute Myocardial Infarction. Circ Cardiovasc Interv. 2020 May;13(5):e008505. doi: 10.1161/CIRCINTERVENTIONS.119.008505. Epub 2020 May 15.

  PMID: 32408817 DERIVED

• McCartney PJ, Maznyczka AM, Eteiba H, McEntegart M, Oldroyd KG, Greenwood JP, Maredia N, Schmitt M, McCann GP, Fairbairn T, McAlindon E, Tait C, Welsh P, Sattar N, Orchard V, Corcoran D, Ford TJ, Radjenovic A, Ford I, McConnachie A, Berry C; T-TIME Investigators. Low-Dose Alteplase During Primary Percutaneous Coronary Intervention According to Ischemic Time. J Am Coll Cardiol. 2020 Mar 31;75(12):1406-1421. doi: 10.1016/j.jacc.2020.01.041.

  PMID: 32216909 DERIVED

• Maznyczka AM, Carrick D, Oldroyd KG, James-Rae G, McCartney P, Greenwood JP, Good R, McEntegart M, Eteiba H, Lindsay MM, Cotton JM, Petrie MC, Berry C. Thermodilution-derived temperature recovery time: a novel predictor of microvascular reperfusion and prognosis after myocardial infarction. EuroIntervention. 2021 Jun 25;17(3):220-228. doi: 10.4244/EIJ-D-19-00904.

  PMID: 32122822 DERIVED

• Maznyczka AM, McCartney PJ, Oldroyd KG, Lindsay M, McEntegart M, Eteiba H, Rocchiccioli P, Good R, Shaukat A, Robertson K, Kodoth V, Greenwood JP, Cotton JM, Hood S, Watkins S, Macfarlane PW, Kennedy J, Tait RC, Welsh P, Sattar N, Collison D, Gillespie L, McConnachie A, Berry C. Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction. J Am Heart Assoc. 2020 Feb 4;9(3):e014066. doi: 10.1161/JAHA.119.014066. Epub 2020 Jan 28.

  PMID: 31986989 DERIVED

• McCartney PJ, Eteiba H, Maznyczka AM, McEntegart M, Greenwood JP, Muir DF, Chowdhary S, Gershlick AH, Appleby C, Cotton JM, Wragg A, Curzen N, Oldroyd KG, Lindsay M, Rocchiccioli JP, Shaukat A, Good R, Watkins S, Robertson K, Malkin C, Martin L, Gillespie L, Ford TJ, Petrie MC, Macfarlane PW, Tait RC, Welsh P, Sattar N, Weir RA, Fox KA, Ford I, McConnachie A, Berry C; T-TIME Group. Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial. JAMA. 2019 Jan 1;321(1):56-68. doi: 10.1001/jama.2018.19802.

  PMID: 30620371 DERIVED

MeSH Terms

Conditions

Myocardial Infarction

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Colin Berry, Prof

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2014
• First Posted: October 6, 2014
• Study Start: March 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: May 8, 2019
• Last Updated: September 6, 2019

Record last verified: 2019-09

Locations

GB (11)