Thrombolysis of Urokinase for Minor Stroke

NCT04420351 | Completed Phase 3 DMC

• 1 other identifier: 2017YFC1308202
• Study Type: interventional
• Target: 1,005
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will enroll patients that have been diagnosed with minor stroke, which has occurred within the past 6 hours. TRUST is a prospective multicenter, randomized, blinded-endpoint study to evaluate the efficacy and safety of Urokinase Thrombolysis for patients with minor stroke.

Conditions

Minor Stroke

Keywords

Thrombolysis; Urokinase; Ischemic stroke

Outcome Measures

Primary Outcomes (2)

• Proportion of patients with a modified Rankin Scale(mRS) of 0 or 1 at 90-day follow-up

  mRS has 0-6 points, the higher the worse outcome.

  90 Days

• Proportion of patients with symptomatic intracranial hemorrhage within 36 hours

  Symptomatic intracranial haemorrhage within 36 hours

  36 hours

Secondary Outcomes (8)

• Proportion of patients with new vascular events

  90 days

• MRS score

  90 days

• The ratio of patients with MRS 0-1 during the last visit in two groups

  90 days

• Changes in National Institutes of Health Stroke Scale(NIHSS) score

  90 days

• Barthel index (BI) score

  90 days

Study Arms (2)

Urokinase thrombolysis

EXPERIMENTAL

The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.

Drug: Urokinase thrombolysis

Antiplatelet treatment

OTHER

The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018

Drug: Aspirin;Clopidogrel

Interventions

Urokinase thrombolysis DRUG

The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.

Also known as: Urokinase

Urokinase thrombolysis

Aspirin;Clopidogrel DRUG

The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018.

Also known as: Antiplatelet treatment

Antiplatelet treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients: 18-80 years old
• The time from last seen well to treatment \< 6 hours
• Minor stroke defined as a baseline NIHSS ≤5 at the time of randomization..
• First onset or pre-stroke mRS≤1
• Informed consent signed

You may not qualify if:

• Hyperdensity on CT suggesting intracranial hemorrhage
• Large acute stroke \>1/3 middle cerebral artery (MCA) territory visible on CT or MRI
• Other contraindications of intravenous thrombolysis, including but not limited to:
• Intracranial tumor, arteriovenous malformation
• Coma or confirmed as severe stroke by clinical assessment (e.g. NIHSS ≥25) or proper imaging methods
• With seizure
• Stroke attack within past three months
• Heparin administration within 48h before onset, with APTT longer than upper limit
• Stroke history with diabetes
• Platelet count ≤100×10\^9/L
• Difficult to control hypertension, defined by systolic pressure ≥185mmHg or diastolic pressure ≥110 mmHg in 3 tests with at least ten minutes interval, under well guided medications.
• Blood glucose \<50mg/dl（2.7mmol/l）or \>400mg/dl（22.2mmol/l）
• Obvious hemorrhage within past 6 months
• Oral anti-coagulation drug administration (e.g. warfarin) with INR\>1.5
• Intracranial hemorrhage or suspected intracranial hemorrhage (including subarachnoid hemorrhage)

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University: lead
• Beijing Tiantan Hospital: collaborator
• Shanghai 10th People's Hospital: collaborator
• General Hospital of Shenyang Military Region: collaborator

Study Sites (1)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 0371, China

Location

Related Publications (12)

• Liu M, Wu B, Wang WZ, Lee LM, Zhang SH, Kong LZ. Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol. 2007 May;6(5):456-64. doi: 10.1016/S1474-4422(07)70004-2.

  PMID: 17434100 BACKGROUND

• Wu Z, Yao C, Zhao D, Wu G, Wang W, Liu J, Zeng Z, Wu Y. Sino-MONICA project: a collaborative study on trends and determinants in cardiovascular diseases in China, Part i: morbidity and mortality monitoring. Circulation. 2001 Jan 23;103(3):462-8. doi: 10.1161/01.cir.103.3.462.

  PMID: 11157701 BACKGROUND

• Liu L, Wang D, Wong KS, Wang Y. Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke. 2011 Dec;42(12):3651-4. doi: 10.1161/STROKEAHA.111.635755. Epub 2011 Nov 3.

  PMID: 22052510 BACKGROUND

• Smith EE, Fonarow GC, Reeves MJ, Cox M, Olson DM, Hernandez AF, Schwamm LH. Outcomes in mild or rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from Get With The Guidelines-Stroke. Stroke. 2011 Nov;42(11):3110-5. doi: 10.1161/STROKEAHA.111.613208. Epub 2011 Sep 8.

  PMID: 21903949 BACKGROUND

• Barber PA, Zhang J, Demchuk AM, Hill MD, Buchan AM. Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology. 2001 Apr 24;56(8):1015-20. doi: 10.1212/wnl.56.8.1015.

  PMID: 11320171 BACKGROUND

• Nedeltchev K, Schwegler B, Haefeli T, Brekenfeld C, Gralla J, Fischer U, Arnold M, Remonda L, Schroth G, Mattle HP. Outcome of stroke with mild or rapidly improving symptoms. Stroke. 2007 Sep;38(9):2531-5. doi: 10.1161/STROKEAHA.107.482554. Epub 2007 Aug 2.

  PMID: 17673713 BACKGROUND

• Smith EE, Abdullah AR, Petkovska I, Rosenthal E, Koroshetz WJ, Schwamm LH. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke. 2005 Nov;36(11):2497-9. doi: 10.1161/01.STR.0000185798.78817.f3. Epub 2005 Oct 6.

  PMID: 16210552 BACKGROUND

• Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, Subramaniam S, Goyal M, Patil S, Menon BK, Barber PA, Dowlatshahi D, Field T, Asdaghi N, Camden MC, Hill MD; TEMPO-1 Investigators. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015 Mar;46(3):769-74. doi: 10.1161/STROKEAHA.114.008504. Epub 2015 Feb 12.

  PMID: 25677596 BACKGROUND

• Khatri P, Tayama D, Cohen G, Lindley RI, Wardlaw JM, Yeatts SD, Broderick JP, Sandercock P; PRISMS and IST-3 Collaborative Groups. Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Patients With Mild Stroke in the Third International Stroke Trial-3: Post Hoc Analysis. Stroke. 2015 Aug;46(8):2325-7. doi: 10.1161/STROKEAHA.115.009951. Epub 2015 Jun 23.

  PMID: 26106113 BACKGROUND

• National Institute of Neurological Disorders Stroke rt-PA Stroke Study Group. Recombinant tissue plasminogen activator for minor strokes: the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study experience. Ann Emerg Med. 2005 Sep;46(3):243-52. doi: 10.1016/j.annemergmed.2005.02.013.

  PMID: 16126134 BACKGROUND

• Khatri P, Kleindorfer DO, Yeatts SD, Saver JL, Levine SR, Lyden PD, Moomaw CJ, Palesch YY, Jauch EC, Broderick JP. Strokes with minor symptoms: an exploratory analysis of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials. Stroke. 2010 Nov;41(11):2581-6. doi: 10.1161/STROKEAHA.110.593632. Epub 2010 Sep 2.

  PMID: 20814000 BACKGROUND

• Tao Y, Gao Y, Zhao L, Xu Y, Jiang C, Liu K, Fang H, Pei L, Wang X, Zhang R, Wu J, Yang J, Han X, Guo H, Xue B, Li J, Liu Y, Gu H, Du K, Cheng X, Dong Q, Wang D, Buonanno FS, Ning M, Xu Y, Song B; TRUST Trial Investigators. Effect of intravenous urokinase vs best medicine treatment on functional outcome for patients with acute minor stroke (TRUST): a randomized controlled trial. BMC Med. 2025 Jan 6;23(1):6. doi: 10.1186/s12916-024-03820-2.

  PMID: 39757192 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Urokinase-Type Plasminogen Activator

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

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

Study Officials

• Bo Song, MD;PhD

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of neurology department

Study Record Dates

• First Submitted: June 4, 2020
• First Posted: June 9, 2020
• Study Start: October 4, 2020
• Primary Completion: February 18, 2023
• Study Completion: February 18, 2023
• Last Updated: November 14, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)