Low-Dose Tenecteplase for Acute Ischemic Stroke Treatment in Aging Patients

Official title

Efficacy and Safety of Low-Dose Tenecteplase for Acute Ischemic Stroke Treatment in Aging Patients: A Prospective, Multicenter, Randomized Controlled Study

Overview

The DATE-AGING study is a prospective, multicenter, randomized controlled trial investigating low-dose tenecteplase in elderly patients with acute ischemic stroke. Its primary objective is to evaluate the safety and efficacy of low-dose tenecteplase in elderly patients within 4.5 hours of acute ischemic stroke onset.

Interventions

• Drug low-dose tenecteplase intravenous thrombolysis
  Subjects will be randomized to low-dose group or standard-dose group in a 1:1 ratio. Patients in the low-dose group received tenecteplase (0.175 mg/kg) for intravenous thrombolysis. The upper dose limit is set to 17.5 mg/patient.
• Drug standard-dose tenecteplase intravenous thrombolysis
  Subjects will be randomized to low-dose group or standard-dose group in a 1:1 ratio. Patients in the standard-dose group received tenecteplase (0.25 mg/kg) for intravenous thrombolysis. The upper dose limit is set to 25 mg/patient.

Primary outcome measures

• Percentage of Participants With Modified Rankin Scale (mRS) Score of 0 or 1 [Time frame: At Day 90±7 days]

Secondary outcome measures (8)

• Percentage of participants with major neurological improvement (National Institutes of Health Stroke Scale (NIHSS) score of 0 or improvement of at least 4 points compared with baseline) [Time frame: At 24 hours]
• Percentage of Participants With Modified Rankin Scale (mRS) Score of 0-2 [Time frame: At Day 90±7 days]
• Distribution of Modified Rankin Scale (mRS) [Time frame: At Day 90±7 days]
• Percentage of Participants With Barthel Index Score ≥95 [Time frame: up to 90 days]
• EQ-5D-5L score [Time frame: At Day 90±7 days]
• Percentage of Participants With Symptomatic Intracerebral Haemorrhage (sICH) [Time frame: up to 36 hours]
• All-cause mortality [Time frame: up to 90 days]
• Percentage of Participants With Modified Rankin Scale (mRS) Score of 5 or 6 [Time frame: At Day 90±7 days]

Eligibility criteria

Inclusion criteria

• Age ≥ 70 years;
• Diagnosis of ischaemic stroke with a measurable neurological deficit on National Institutes of Health Stroke Scale (NIHSS) (1≤ NIHSS ≤25); if NIHSS <4, patients have to be with at least a measurable deficit on motor power (upper or lower limbs ≥1);
• Stroke symptoms should have been present for at least 30 minutes (min) without significant improvement prior to randomisation;
• Thrombolytic therapy can be initiated within 4.5 Hour(s) (h) of Acute ischaemic stroke (AIS) onset;
• Patients with premorbid modified Rankin Scale (mRS) 0 or 1;
• Informed consent from the patient or surrogate.

Exclusion criteria

• Imaging demonstrates multi-lobar infarction (hypodensity >1/3 cerebral hemisphere);
• Acute bleeding diathesis or allergy to tenecteplase, including but not limited to

• Known genetic predisposition to bleeding or significant bleeding disorder at present or within the past 6 Month(s) (m)
• Administration of heparin within the previous 48 h and activated partial thromboplastin time (aPTT) exceeding the upper limit of normal for laboratory measurement
• Current use of vitamin K based oral anticoagulants (e.g. warfarin) and a prolonged prothrombin time (International normalised Ratio (INR) > 1.7 or Prothrombin time (PT)>15 seconds (s)) or current use of novel oral anticoagulants (i.e. dabigitran, rivaroxiban, or apixiban) with prolongation of activated partial thromboplastin time (aPTT) and/or PT above the upper limit of the local laboratory reference range
• Platelet count of below 100×10\^9/ L
• Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
• Recent traumatic external heart massage or recent puncture of a non-compressive blood-vessel (e.g. subclavian or jugular vein puncture) , within the past 10 days
• Known history of suspected intracranial haemorrhage or suspected subarachnoid haemorrhage from aneurysm
• Neoplasm with increased haemorrhagic risk
• Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial aneurysm, or arterial/venous malformations
• History of significant trauma or major surgery within the past 3 months.
• Any known disorder associated with a significant increased risk of bleeding
• Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.);
• Blood glucose <2.8 mmol/L or >22.22 mmol/L;
• After active antihypertensive treatment, hypertension is still not under control: systolic blood pressure ≥180 mmHg, or diastolic blood pressure ≥100 mmHg;
• Seizure at stroke onset;
• Concurrent malignancy or severe systemic disease with an anticipated survival of less than 90 days;
• Participation in other clinical trials within 3 months prior to screening;
• Unsuitability or participation in this study as judged by the Investigator may result in subjects being exposed to greater risk.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 51 centers

• Southwest Hospital, Chongqing, China — Chongqing
• Wuchang People's Hospital — Harbin
• Shenqiu County People's Hospital — Zhoukou
• Anshan Changda Hospital — Anshan
• Anyang People's Hospital — Anyang
• Huaxian People's Hospital of Henan — Anyang
• Baoshan People's Hospital — Baoshan
• People's Hospital of Zhijin County — Bijie
• … and 43 more centers

Identifiers

NCT: NCT07294209 · 2025IITDA10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗