Scribd
Upload
10 views23 pages

Journal Club

Uploaded by

albadrimohammed1997
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
10 views23 pages

Journal Club

Uploaded by

albadrimohammed1997
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 23

Journal club

Mohamed Al Badri R1 Neurology


Department of internal medicine, SQUH
Muscat, Sultanate of Oman
Outline

• Introduction
• Previous trials: TRACE 2 & TIMELESS
• TRACE 3 Trial aim and methodology
• Results
• Conclusion
Ischemic stroke

• Sudden onset of neurological deficits of a vascular etiology with infarction of CNS


tissue.
• two major types: ischemic (~80%) and hemorrhagic (~20%)
Introduction

• IV thrombolytic agents is recommended for eligible patients within 4.5 hours after
the onset of stroke
• Tenecteplase has been shown to be noninferior to alteplase
• Approximately 67 to 75% of patients present after 4.5 hours after stroke onset or with
an unknown time of onset.
• Alteplase therapy is beneficial when initiated up to 9 hours after the onset of stroke if
perfusion imaging results indicate the presence of salvageable ischemic brain tissue.
. Powers WJ, Rabinstein AA, Ackerson
T, et al. Guidelines for the early manage-
ment of patients with acute ischemic
stroke: 2019 update to the 2018 guide-
lines for the early management of acute
ischemic stroke: a guideline for health-
care professionals from the American Heart
Association/American Stroke Association.
Stroke 2019; 50(12): e344-e418.
2. Alamowitch S, Turc G, Palaiodimou L,
et al. European Stroke Organisation (ESO)
expedited recommendation on tenecteplase
for acute ischaemic stroke. Eur Stroke J
2023; 8: 8-54.
3. Tong D, Reeves MJ, Hernandez AF, et
al. Times from symptom onset to hospital
arrival in the Get With The Guidelines–
Stroke program 2002 to 2009: temporal
trends and implications. Stroke 2012; 43:
1912-7.
4. Thomalla G, Simonsen CZ, Boutitie F,
et al. MRI-guided thrombolysis for stroke
with unknown time of onset. N Engl J Med
2018; 379: 611-22.
TIMELESS Trial
The Tenecteplase Reperfusion Therapy in Acute
Ischemic Cerebrovascular Events (TRACE Trial)
TRACE 2 Trial
Can we give tenectables after 4.5 hrs
without access to thrombectomy?
TRACE 3

• Investigated the efficacy and safety of tenecteplase at a dose of 0.25 mg per


kilogram of body weight, administered 4.5 to 24 hours after stroke onset in patients
who had had ischemic stroke resulting from large-vessel occlusion, had
salvageable tissue, and did not have access to endovascularthrombectomy.
Aim and objectives

• Research problem: The effect of late administration of tenecteplase after 4.5 hours
of stroke onset in patients without immediate access to thrombectomy is currently
unclear and is relevant to a majority of patients worldwide.
• Efficacy and safety of tenecteplase administered 4.5 hr to 24 hours after stroke onset
in patient with LVO with salvegable tissue and did not have access to Thrombectomy
Methods

• Phase 3, multicente, prospective, open label, randomized, blinded outcome trial


• Study was conducted at 58 centers in China
• End point outcome was evaluated by a qualified blind evaluation study physician who
does not know the treatment group.
Pre stroke
mRS NIHSS
0 OR 1 6-25 ICA
MCA M1/2 Ischemic core volume <70 mL
mismatch ratio≥1.8
Age ≥18 years old mismatch volume≥15 mL
LAST SEEN NORMAL 4.5-24 HR

Was the assignment


Patient of patients
randomly tointreatments
assigned 1:1 ratio randomized?

Intention to treat
analysis

Rescue MT

Intention to treat & per-protocol analysis


Exclusion criteria
1. Intended to proceed to endovascular treatment; (NB patients taking antiplatelet medication can be included);
2. Allergy to tenecteplase; 10.Ischemic stroke or myocardial infarction in previous 3 months, previous
intracranial hemorrhage, severe traumatic brain injury or intracranial or
3. Rapidly improving symptoms at the discretion of the investigator; intraspinal operation in previous 3 months, or known intracranial
4. NIHSS consciousness score 1a >2, or epileptic seizure, hemiplegia after neoplasm, arteriovenous malformation or giant aneurysm;
seizures ( Todd's palsy ) or other neurological/mental illness such that the 11.Any terminal illness such that the patient would not be expected to
patient is not able to cooperate or unwilling to cooperate; survive more than 1 year;
5. Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic 12.Unable to perform CTP or PWI;
≥100 mmHg), despite blood pressure-lowering treatment;
13.Hypodensity in >1/3 MCA territory on non-contrast CT;
6. Blood glucose <2.8 or >22.2 mmol/L (point of care glucose testing is
acceptable ); 14.Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI;
7. Active internal bleeding or at high risk of bleeding, e.g., major surgery, 15.Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion
trauma or gastrointestinal or urinary tract hemorrhage within the previous accompanied with basilar occlusion);
21 days, or arterial puncture at a non-compressible site within the
previous 7 days; 16.Pregnant women, nursing mothers, or reluctant to use effective
contraceptive measures during the period of trial;
8. Any known impairment in coagulation due to comorbid disease or
anticoagulant use. If on warfarin, then INR >1.7 or prothrombin time >15 17.Unlikely to adhere to the trial protocol or follow-up;
seconds; use of any direct thrombin inhibitors or direct factor Xa inhibitors 18.Any condition that, in the judgment of the investigator could impose
during the last 48 hours unless reversal of effect can be achieved with a hazards to the patient if study therapy is initiated or affect the participation
reversal agent; any full dose heparin/heparinoid during the last 24 hours of the patient in the study;
or with an elevated aPTT greater than the upper limit of normal;
19.Participation in other interventional clinical trials within the previous 3
9. Known defect of platelet function or platelet count below 100,000/mm3 months.
Were the groups similar at the
start of the trial?
Were all patients who entered the trial accounted for? And
analyzed in the groups to which they were randomized?
• Patients who are subsequently judged to require endovascular treatment after
intravenous thrombolysis in the judgement of the investigator will be included in
the intention-­to-­treat analysis, but will be excluded from per-­protocol
analysis in order to avoid the effect on the outcome.

• Protocol violations were reported in 28 participants:


1. 9 had unrecognized cerebral infarction in >1/3 of MCA territory
2. 9 Rescue endovascular thrombectomy (4 in tenecteplase arm)
Results
External validity/applicability of the study to our practice

• The trial excluded patients who presented to thrombectomy capable centers


• Only conducted on chines population
• Trial only included ICA, MCA M1 and M2 only

You might also like

pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy