Early minimally invasive catheter evacuation with thrombolysis for intracerebral hemorrhage

TrIal of Early Minimally Invasive Catheter Evacuation With Thrombolysis in IntraCerebral Hemorrhage (TIME-ICH): A Prospective, Multi-center, Open-label, Adaptive, Randomized Controlled Trial

This trial tests whether early minimally invasive catheter clot removal combined with thrombolysis helps adults with acute spontaneous supratentorial intracerebral hemorrhage (≥20 mL) recover better than best medical care.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 750 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Xuanwu Hospital, Beijing (other)
• Locations: 50 sites (Guangdong, Yuexiu and 49 other locations)
• Trial ID: NCT07187687 on ClinicalTrials.gov

What this trial studies

TIME-ICH is a multicenter, randomized, adaptive PROBE trial comparing early minimally invasive surgery with catheter-based clot evacuation plus intraparenchymal thrombolysis (eMIST) to best medical management in adults with spontaneous supratentorial ICH of at least 20 mL. Eligible patients who can be randomized within 8 hours of symptom onset and start the intervention within 4 hours after randomization are allocated 1:1 by central computerized randomization. The trial uses blinded assessment of the 180-day utility-weighted modified Rankin Scale as the primary efficacy endpoint and includes an adaptive sample size re-estimation after 250 patients complete 180-day follow-up. The design aims to determine whether early clot reduction improves long-term functional outcomes compared with medical care alone.

Who should consider this trial

Good fit: Adults (≥18 years) with acute spontaneous supratentorial ICH ≥20 mL on CT, pre-stroke mRS 0–1, able to be randomized within 8 hours of onset and start the intervention within 4 hours after randomization are ideal candidates.

Not a fit: Patients with infratentorial hemorrhage, secondary causes of bleeding (aneurysm, AVM, tumor, venous thrombosis), CT angiography 'spot sign', recent prior ICH, uncontrolled medical instability, or who cannot meet the tight timing windows are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the procedure could reduce disability and improve 180-day functional outcomes for patients with large spontaneous supratentorial ICH.

How similar studies have performed: Related minimally invasive evacuation approaches such as the MISTIE trials reduced hematoma volume and showed signals for benefit in selected patients but did not definitively prove a broad functional outcome advantage, so the approach remains promising but not conclusively proven.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years;
2. Pre-randomization head CT demonstrating an acute, spontaneous, primary ICH;
3. ICH volume ≥ 20mL as calculated by the ABC/2 method;
4. The randomization can be completed within 8 hours after the onset of stroke symptoms (or the time last known to be well), and study intervention can reasonably be initiated within 4 hours after randomization.
5. Historical Modified Rankin Score 0 or 1;
6. Obtain informed consent from patient or legal representative.

Exclusion Criteria:

1. Infratentorial intraparenchymal hemorrhage including midbrain, pontine, or cerebellar;
2. Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, venous sinus thrombosis, mass or tumor, hemorrhagic conversion of an ischemic infarct, tumor stroke, recurrence of a recent (\<1 year) ICH, as diagnosed with radiographic imaging;
3. Presence of spot sign in CT angiography;
4. Blood pressure control before randomization is ineffective, systolic blood pressure \> 220 mmHg;
5. Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4;
6. Hemorrhage with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions;
7. Intraventricular extension of the Hemorrhage is visually estimated to involve \>50% of either of the lateral ventricles;
8. Any irreversible coagulopathy or known clotting disorder.
9. Platelet count \< 750,000, INR \> 1.4 after correction
10. Patients requiring long-term anti-coagulation that needs to be initiated \< 30 days from index ICH;
11. Use of 2 or more antithrombotic drugs prior to symptom onset;
12. Patients with a mechanical heart valve;
13. Positive urine or serum pregnancy test in female subjects without documented history of surgical sterilization or is post-menopausal;
14. Urokinase allergy;
15. Any concurrent serious illness that would interfere with the outcome assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease;
16. Inability or unwillingness of patient or legal representative to give written informed consent;
17. Known life-expectancy of less than 6 months;
18. Participation in a concurrent interventional medical investigation or clinical trial.

Where this trial is running

Guangdong, Yuexiu and 49 other locations

• Guangdong Provincial People's Hospital — Guangdong, Yuexiu, China (NOT_YET_RECRUITING)
• Guangde People's Hospital — Anhui, China (NOT_YET_RECRUITING)
• Beijing Chao-Yang Hospital, Capital Medical University — Beijing, China (NOT_YET_RECRUITING)
• Beijing Daxing District People's Hospital — Beijing, China (RECRUITING)
• Beijing Fengtai You'anmen Hospital — Beijing, China (RECRUITING)
• Beijing Friendship Hospital, Capital Medical University — Beijing, China (RECRUITING)
• Peking University Aerospace Central Hospital — Beijing, China (NOT_YET_RECRUITING)
• Shunyi District Hospital in Beijing — Beijing, China (NOT_YET_RECRUITING)
• Xuanwu Hospital, Capital Medical University — Beijing, China (RECRUITING)
• Bozhou city people's hospital — Bozhou, China (NOT_YET_RECRUITING)
• Changsha Central Hospital — Changsha, China (RECRUITING)
• Changzhi Medical College Affiliated Heji Hospital — Changzhi, China (RECRUITING)
• Chifeng Municipal Hospital — Chifeng, China (RECRUITING)
• Chongqing Emergency Medical Service — Chongqing, China (RECRUITING)
• First Affiliated Hospital of Dalian Medical University — Dalian, China (NOT_YET_RECRUITING)
• Fuxin Second People\'s Hospital — Fuxin, China (NOT_YET_RECRUITING)
• First Affiliated Hospital of Gannan Medical University — Gannan, China (NOT_YET_RECRUITING)
• The Seventh Affiliated Hospital of Southern Medical University — Guangdong, China (NOT_YET_RECRUITING)
• The First Hospital of Harbin Medical University — Harbin, China (NOT_YET_RECRUITING)
• Affiliated Hospital of Hebei University of Engineering — Hebei, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Anhui Medical University — Hefei, China (RECRUITING)
• Affiliated Hospital of Inner Mongolia Medical University — Hohhot, China (NOT_YET_RECRUITING)
• Jinan City People's Hospital — Jinan, China (RECRUITING)
• Jinan Hospital of Xuanwu Hospital, Capital Medical University — Jinan, China (NOT_YET_RECRUITING)
• The First People Hospital of Yunnan Province — Kunming, China (RECRUITING)
• Tibet People's Hospital — Lhasa, China (NOT_YET_RECRUITING)
• Liaocheng Brain Hospital — Liaocheng, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Nanchang University — Nanchang, China (RECRUITING)
• Affiliated Hospital of Nantong University — Nantong, China (NOT_YET_RECRUITING)
• Center Hospital of Nanyang — Nanyang, China (NOT_YET_RECRUITING)
• Third People's Hospital of Hainan Province — Sanya, China (RECRUITING)
• Shanghai Fourth People's Hospital Affiliated to Tongji University — Shanghai, China (RECRUITING)
• Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University — Shanghai, China (NOT_YET_RECRUITING)
• Shanghai Tenth People's Hospital — Shanghai, China (RECRUITING)
• The First Affiliated Hospital of China Medical University — Shenyang, China (NOT_YET_RECRUITING)
• The First Hospital of Hebei Medical University — Shijiazhuang, China (RECRUITING)
• Suining Central Hospital — Sichuan, China (NOT_YET_RECRUITING)
• Central People's Hospital of Siping City — Siping, China (RECRUITING)
• The Second Affiliated Hospital of Shandong First Medical University — Tai’an, China (RECRUITING)
• Tianjin Huanhu Hospital — Tianjin, China (RECRUITING)
• First Affiliated Hospital of Xinjiang Medical University — Ürümqi, China (RECRUITING)
• Weifang People's Hospital — Weifang, China (RECRUITING)
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, China (RECRUITING)
• The Second Affiliated Hospital of Wenzhou Medical University — Wenzhou, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Xiamen University — Xiamen, China (NOT_YET_RECRUITING)
• Xiangyang Central Hospital — Xiangyang, China (NOT_YET_RECRUITING)
• Yanan Medical College of Yanan University — Yan’an, China (RECRUITING)
• Henan Provincial People's Hospital — Zhengzhou, China (RECRUITING)
• The Second Affiliated Hospital of Zhengzhou University — Zhengzhou, China (RECRUITING)
• The Fourth People's Hospital of Zigong City — Zigong, China (RECRUITING)

Study contacts

• Study coordinator: Tao Hong, MD, PhD

Conditions: Intracerebral Hemorrhage, Intracranial Hemorrhages, ICH, brain hemorrhage, Hemorrhage, Cerebrovascular Disorders, Brain Diseases, Minimally invasive catheter evacuation