Efficacy and Safety of Human Urinary Kallidinogenase for Acute Ischemic Stroke Patients Receiving Reperfusion Treatment

Overview

This study aims to explore the efficacy and safety of Human Urinary Kallidinogenase for acute ischemic stroke patients receiving intravenous thrombolysis and/or endovascular treatment.

Detailed description

Within 24 hours after symptom onset, eligible participants will be randomly assigned in a 1:1 ratio to the HUK or placebo group, receiving adjunctive HUK or placebo treatment alongside standard intravenous thrombolysis and/or endovascular treatment. All participants will be recommended to continuously inject drugs or placebo for 10 to 14 days according to length of hospitalization.

* Intervention group: HUK (0.15 PNA) and sodium chloride injection (100ml), once per day * Control group: placebo (0 PNA) and sodium chloride injection (100ml), once per day The total follow-up duration is 90 days.

Interventions

• Drug Human urinary kallidinogenase (HUK)
  HUK (0.15 PNA) and sodium chloride injection (100ml), once per day
• Drug Placebo
  placebo (0 PNA) and sodium chloride injection (100ml), once per day

Primary outcome measures

• Proportion of a favorable outcome (mRS 0-2) [Time frame: at 90 days]

Secondary outcome measures (9)

• Proportion of a favorable outcome (mRS 0-2) [Time frame: at 14 days]
• Proportion of an excellent outcome (mRS 0-1) [Time frame: at 90 days]
• Distribution of mRS score [Time frame: at 90 days]
• Improvement of NIHSS score [Time frame: at 14 days]
• Risk of recurrent symptomatic stroke [Time frame: within 90 days]
• Risk of recurrent symptomatic ischemic stroke [Time frame: within 90 days]
• Risk of combined vascular events [Time frame: within 90 days]
• Improvement of EQ-5D-5L [Time frame: at 90 days]
• Improvement of MOCA [Time frame: at 90 days]

Eligibility criteria

Inclusion criteria

• Age ≥18 years.
• Having anterior circulation AIS within 24 hours of onset.
• The NIHSS score at enrollment is 4 to 25.
• Receiving intravenous recombinant tissue plasminogen activator (rt-PA) or TNK-tPA, or endovascular treatment including intra-arterial thrombolysis, mechanical thrombectomy, or intravenous rt-PA /TNK-tPA bridging endovascular treatment.
• Being independent in daily activities (mRS ≤1) before onset.
• Patients or their legal representatives are able and willing to sign informed consent forms.

Exclusion criteria

• Having an Alberta Stroke Program Early Computed Tomography Score (ASPECT) score of 6 or less confirmed by preoperational computed tomography scan.
• Being already treated with HUK or any drugs containing HUK after onset.
• Having an allergy history of HUK or drugs containing HUK, or other drugs and food.
• Having a history of coagulation dysfunction, systemic bleeding, or thrombocytopenia; having hemorrhagic diseases at the time of enrollment, including cerebral hemorrhage, subarachnoid hemorrhage, epidural or subdural hematoma, gingival bleeding, gastrointestinal bleeding, dermal ecchymosis, etc; taking anticoagulants including warfarin, rivaroxaban, etc.; or taking heparin within 48 hours after stroke onset.
• Taking angiotensin-converting enzyme inhibitor (ACEI) antihypertensive drugs regularly within one week before enrollment, including captopril, enalapril, benazepril, etc.
• Having chronic liver disease or liver dysfunction, with elevated ALT/AST (>3.0×ULN ); or having kidney dysfunction or receiving dialysis, with elevated serum creatinine (>2.0×ULN).
• Having severe cardiopulmonary disease that are deemed unsuitable for the study by the investigators.
• Having contraindications for intravenous thrombolysis or endovascular treatment, including intra-arterial thrombolysis, mechanical thrombectomy, or intravenous rt-PA /TNK-tPA bridging endovascular treatment.
• Having lethal diseases with a life expectancy < 3 months.
• Being pregnant or lactating; or women of child-bearing age not taking effective contraception, or having no negative pregnancy test record.
• Being unable to complete the study due to mental illness, cognitive or emotional disorder, physical condition, geographical factors, etc.
• Participating in another clinical trial currently.
• Other conditions that investigators consider he/she is not appropriate to participate in this study.

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

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital, Capital Medical University — Beijing

Publications

• Wang Y, Xu J, Zhao X, Wang D, Wang C, Liu L, Wang A, Meng X, Li H, Wang Y. Association of hypertension with stroke recurrence depends on ischemic stroke subtype. Stroke. 2013 May;44(5):1232-7. doi: 10.1161/STROKEAHA.111.000302. Epub 2013 Feb 26. PMID 23444308
• Pan Y, Li Z, Li J, Jin A, Lin J, Jing J, Li H, Meng X, Wang Y, Wang Y. Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention. J Stroke. 2021 Jan;23(1):51-60. doi: 10.5853/jos.2020.03391. Epub 2021 Jan 31. PMID 33600702
• Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, ag PMID 25106063
• Asadi H, Dowling R, Yan B, Wong S, Mitchell P. Advances in endovascular treatment of acute ischaemic stroke. Intern Med J. 2015 Aug;45(8):798-805. doi: 10.1111/imj.12652. PMID 25443686
• Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser PMID 25517348
• Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF PMID 25671798
• Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA PMID 25671797
• Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):22 PMID 25882376

Identifiers

NCT: NCT06848894 · KY2024-320-04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗