Impact of Apixaban on Clinical Outcome of the Patients With Large Vessel Occlusion or Stenosis Trial

Ischemic Stroke Clinical Trial

— ALVO  

Official title:

Impact of Apixaban on Clinical Outcome of the Patients With Large Vessel Occlusion or Stenosis Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02818868
• Other study ID #: 2157
• Status: Completed
• Start date: July 2016
• Est. completion date: February 2018

Study information

• Verified date: November 2016
• Source: Hyogo College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study is to investigate the clinical events of the patients with acute cerebral large vessel occlusion or stenosis and atrial fibrillation, treated by apixaban within 14 days after onset. This is the observational study that patients will be made the registration at the timing of both retrospective period and prospective period.

Description:

Four novel oral anticoagulants (NOACs) have been released to the market ahead of any county in the world. However, no information is available on the clinical results of NOACS and their secondary preventive effects in Japanese population.

Medical care for acute-phase stroke is constantly advancing. Specifically, in addition to thrombolytic activator tissue plasminogen activator (t-PA), advancement of endovascular thrombectomy has made it possible to treat patients who would not have been saved otherwise. In Japan, cerebrovascular accident had been the third leading cause of death, but now has dropped to the forth thanks to wide use of various treatments. Nevertheless, patients often suffer from severe sequelae after stroke, even if they survive. In other words, major challenge in the treatment of stroke is not only to save the patients but also to improve the long-term prognosis.

In large-scale study, NOAC showed an equal to or greater efficacy in preventing recurrence of stroke compared with warfarin and significantly reduced the incidence of bleeding complications. Furthermore, Aristotle trial comparing apixaban vs. warfarin demonstrated that apixaban provided a significant prevention of stroke recurrence as well as significant reduction of bleeding complications and deaths.

Heparin and warfarin had been used as the mainstream agents for the prevention of recurrence after hyperacute phase treatment.However, Aristotle trial showed that there was a significant difference in thromboembolic events between apixaban treatment (1.27 %/year) and warfarin (1.60%/year) (RR 0.79, p<0.01). Also, major bleeding events were less frequent in the patients with apixaban treatment (2.13 %/year) compared to those with warfarin (3.09%/year) (RR 0.69, p<0.001). This study is conducted on the basis of expectation that the use of apixaban in place of traditional warfarin therapy further improve prognosis and reduce bleeding complications in Japanese patients with acute occlusion of major cerebral artery. Additionally, the study will analyze the correlation of the use of apixaban with the prognosis and the incidence of bleeding/ischemic events in patients with intracranial artery stenosis greater than 50% and with atrial fibrillation

Recruitment information / eligibility

• Status: Completed
• Enrollment: 700
• Est. completion date: February 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Patients 20 years and older with acute stroke and treated with oral apixaban within 14 days after onset.

2. Patients who are hospitalized in a period from Oct 1, 2014 to Feb 28, 2018

3. Patients with acute cerebral large vessel occlusion or stenosis (> 50%)

4. Patients with non-valvular atrial fibrillation

5. Patients who are not confirmed ICH by MRI or CT within 24 hours after r-tPA infusion.

Exclusion Criteria:

1. Patients who are considered to be ineligible for the study participation by the investigator.

2. Patients who are pregnant or potentially pregnant.

3. Patients who have a history of hypersensitivity to apixaban

4. Patients with hepatic disease having coagulation disorder and clinically important bleeding risk

5. Patients with renal failure (creatinine clearance < 15 mL/min) 6)Patients with Active pathological bleeding including intracranial bleeding of any type

Related Conditions & MeSH terms

• Ischemic Stroke

Intervention

Drug:
• apixisaban

Locations

Country	Name	City	State
Japan	Hyogo collage of Medicine	Nishinomiya	Hyogo

Sponsors (1)

Lead Sponsor	Collaborator
Hyogo College of Medicine

Country where clinical trial is conducted

Japan, 

References & Publications (20)

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Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kummer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spi — View Citation

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Flint AC, Duckwiler GR, Budzik RF, Liebeskind DS, Smith WS; MERCI and Multi MERCI Writing Committee. Mechanical thrombectomy of intracranial internal carotid occlusion: pooled results of the MERCI and Multi MERCI Part I trials. Stroke. 2007 Apr;38(4):1274 — View Citation

Hirano T, Sasaki M, Mori E, Minematsu K, Nakagawara J, Yamaguchi T; Japan Alteplase Clinical Trial II Group. Residual vessel length on magnetic resonance angiography identifies poor responders to alteplase in acute middle cerebral artery occlusion patient — View Citation

IMS II Trial Investigators. The Interventional Management of Stroke (IMS) II Study. Stroke. 2007 Jul;38(7):2127-35. Epub 2007 May 24. — View Citation

Kelly ME, Furlan AJ, Fiorella D. Recanalization of an acute middle cerebral artery occlusion using a self-expanding, reconstrainable, intracranial microstent as a temporary endovascular bypass. Stroke. 2008 Jun;39(6):1770-3. doi: 10.1161/STROKEAHA.107.506 — View Citation

Lewandowski CA, Frankel M, Tomsick TA, Broderick J, Frey J, Clark W, Starkman S, Grotta J, Spilker J, Khoury J, Brott T. Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke ( — View Citation

Mocco J, Hanel RA, Sharma J, Hauck EF, Snyder KV, Natarajan SK, Linfante I, Siddiqui AH, Hopkins LN, Boulos AS, Levy EI. Use of a vascular reconstruction device to salvage acute ischemic occlusions refractory to traditional endovascular recanalization met — View Citation

Mori E, Minematsu K, Nakagawara J, Yamaguchi T, Sasaki M, Hirano T; Japan Alteplase Clinical Trial II Group. Effects of 0.6 mg/kg intravenous alteplase on vascular and clinical outcomes in middle cerebral artery occlusion: Japan Alteplase Clinical Trial I — View Citation

Nezu T, Koga M, Nakagawara J, Shiokawa Y, Yamagami H, Furui E, Kimura K, Hasegawa Y, Okada Y, Okuda S, Kario K, Naganuma M, Maeda K, Minematsu K, Toyoda K. Early ischemic change on CT versus diffusion-weighted imaging for patients with stroke receiving in — View Citation

Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, Liebeskind DS, Smith WS; TREVO 2 Trialists. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised tria — View Citation

Ogawa A, Mori E, Minematsu K, Taki W, Takahashi A, Nemoto S, Miyamoto S, Sasaki M, Inoue T; MELT Japan Study Group. Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolis — View Citation

Penumbra Pivotal Stroke Trial Investigators. The penumbra pivotal stroke trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease. Stroke. 2009 Aug;40(8):2761-8. doi: 10.1161 — View Citation

Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007 Mar;38(3):967-73. Epub 2007 Feb 1. — View Citation

Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, Clark W, Budzik R, Zaidat OO; SWIFT Trialists. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inf — View Citation

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Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G; SITS-MOST investigators. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implement — View Citation

Yoshimura S, Sakai N, Okada Y, Kitagawa K, Kimura K, Tanahashi N, Hyogo T, Yamagami H, Egashira Y; Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism (RESCUE)-Japan Registry Investigators. Efficacy of endovascular treatment for acute cereb — View Citation

Zaidat OO, Yoo AJ, Khatri P, Tomsick TA, von Kummer R, Saver JL, Marks MP, Prabhakaran S, Kallmes DF, Fitzsimmons BF, Mocco J, Wardlaw JM, Barnwell SL, Jovin TG, Linfante I, Siddiqui AH, Alexander MJ, Hirsch JA, Wintermark M, Albers G, Woo HH, Heck DV, Le — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death		90 days after disease onset
Primary	Ischemic events		90 days after disease onset
Primary	Bleeding events		90 days after disease onset
Secondary	modified Rankin Scale		90 days (±10 days) and 365days(±10 days) after disease onset
Secondary	Death		30 days and 365day
Secondary	Ischemic event		30 days and 365day
Secondary	Bleeding event		30 days and 365day
Secondary	Significant bleeding (ISTH)	scale bleeding events Among the major bleeding , according to the society and hemostasis of international thrombosis (ISTH) bleeding criteria , those that fall under any of the following criteria .; lethal bleeding; important sites or symptomatic bleeding of organs ( intracranial, bone marrow , in the eye , retroperitoneal , intra-articular , or heart sac bleeding , or muscle hemorrhage with a compartment syndrome ); hemoglobin value has decreased 2 g / dL or more bleeding , whole blood transfusion or red blood cells ( more than 2 units) bleeding that required blood transfusion	30 days 90 days (±10 days) and 365day
Secondary	Symptomatic intracranial hemorrhage (sICH)	scale; Symptomatic intracranial hemorrhage (SICH): new intracranial hemorrhage , which corresponds to one of the following: 1) which compared to the worse just before the NIHSS, admitted the deterioration of more than 4 points 2 ) that recognized the deterioration of two or more points in one of the NIHSS category 3 ) intubation / outside decompression / drainage detention or other things that led to the expensive medical / surgical intervention 4 ) it is not a worsening due to other causes	0 days, 90 days and 365days
Secondary	Ischemic stroke and systemic embolism	systemic embolism defined as an event in which the cases with embolism of extremity arteries, intestinal arteries, renal arteries, etc., accompanied by symptoms of local organs.	30 days, 90 days and 365days