The Effect of Early Administration of PCSK9 Inhibitor to Acute Ischemic Stroke Patients Associated With Atherosclerosis on the Stroke Prognosis and Lipid Profile

NCT06083961 | Not Yet Recruiting Phase 4

• 1 other identifier: PCSK9_001
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors) in acute ischemic stroke patients associated with atherosclerosis by investigating

1. 1.the change in lipid profile compared to baseline results
2. 2.the effects on prognosis of stroke The participants will be given PCSK9 inhibitor right after confirmation of acute ischemic stroke, and the investigators will compare the results to the control group, whom are acute ischemic stroke patients treated with conventional lipid lowering therapy, statin and/or ezetimibe.

Conditions

Stroke, Acute Ischemic; PCSK9 Inhibitor

Outcome Measures

Primary Outcomes (2)

• LDL change rate

  The change rate of LDL in PCSK9 inhibitor treated group (alirocumab group) compared to standard of care group.

  LDL level at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).

• Achievement rate to target LDL level

  The investigators intend to use 3 different criteria - 1. LDL under 70mg/dl 2. LDL under 55mg/dL 3. LDL decrement over 50% compared to baseline (day0 LDL)

  LDL target achievement rate at day-1 of hospitalization, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).

Secondary Outcomes (17)

• Change of total cholesterol(TC)

  TC levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).

• Change triglyceridTG)

  TG levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).

• Change of High density lipoprotein(HDL)

  HDL levels are checked all together with LDL level, which is at initial state (before injection, day-0), day-1, day-3, before discharge (normally day-5 to day-7), and day-30 (Outpatient department follow up).

• Change of Apolipoprotein-B

  Apolipoprotein-B is collected at day-1, once.

• Change of Lipoprotein-A

  Lipoprotein-A are collected at day-1, once.

Study Arms (2)

Alirocumab

EXPERIMENTAL

The treatment group patients will receive an additional PCSK9 inhibitor (alirocumab 300mg once) at emergency departement in addition to statin therapy, which is conventional medication given for acute ischemic stroke.

Drug: Alirocumab

Standard of care

NO INTERVENTION

The control group patients will receive standard and conventional acute ischemic stroke treatment, which includes statin therapy.

Interventions

Alirocumab DRUG

Initial alirocumab, single dose of 300mg, subcutaneous injection

Also known as: Praluent

Alirocumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-cardioembolic Stroke
• Acute Ischemic stroke within 7 days of symptom onset (confirmed by CT or MRI)
• Age 19 and above
• Significant stenosis associated with atherosclerosis in major intracranial / extracranial vessels.
• National Institutes of Health Stroke Scale(NIHSS) score of 15 or less at admission
• Patients with the capacity to consent for participation in the clinical trial.

You may not qualify if:

• Presence of high-risk factors for cardioembolism
• Risk of ischemic stroke due to thrombosis from other causes
• Patients with hemorrhagic stroke, brain tumors, or brain abscesses
• Patients unable to take statins or PCSK9 inhibitors
• Pre-stroke mRS score of 3 or higher
• Severe liver failure (liver enzyme \> 3 times the upper normal limit) or renal failure (serum Creatinine \> 2mg/dL or estimated glomerular filtration rate \< 30 mL/min/1.73m2)
• Anemia (hemoglobin \< 8mg/dL) or thrombocytopenia (platelet count \< 100K)
• Uncontrolled diabetes not managed by medication or insulin
• Pregnant or breastfeeding patients
• Patients already receiving PCSK-9 inhibitors
• Patients deemed inappropriate for participation in the clinical trial by the investigator for other reasons.

Sponsors & Collaborators

• Sun U. Kwon: lead

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

Location

Related Publications (13)

• Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8.

  PMID: 15007110 BACKGROUND

• Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4;285(13):1711-8. doi: 10.1001/jama.285.13.1711.

  PMID: 11277825 BACKGROUND

• Penson PE, Pirro M, Banach M. LDL-C: lower is better for longer-even at low risk. BMC Med. 2020 Oct 8;18(1):320. doi: 10.1186/s12916-020-01792-7.

  PMID: 33032586 BACKGROUND

• Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018 Nov 29;379(22):2097-2107. doi: 10.1056/NEJMoa1801174. Epub 2018 Nov 7.

  PMID: 30403574 BACKGROUND

• Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.

  PMID: 28304224 BACKGROUND

• Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143. doi: 10.1161/CIR.0000000000000625. Epub 2018 Nov 10.

  PMID: 30586774 BACKGROUND

• Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-188. doi: 10.1093/eurheartj/ehz455. No abstract available.

  PMID: 31504418 BACKGROUND

• Koskinas KC, Windecker S, Pedrazzini G, Mueller C, Cook S, Matter CM, Muller O, Haner J, Gencer B, Crljenica C, Amini P, Deckarm O, Iglesias JF, Raber L, Heg D, Mach F. Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS). J Am Coll Cardiol. 2019 Nov 19;74(20):2452-2462. doi: 10.1016/j.jacc.2019.08.010. Epub 2019 Aug 31.

  PMID: 31479722 BACKGROUND

• Leucker TM, Blaha MJ, Jones SR, Vavuranakis MA, Williams MS, Lai H, Schindler TH, Latina J, Schulman SP, Gerstenblith G. Effect of Evolocumab on Atherogenic Lipoproteins During the Peri- and Early Postinfarction Period: A Placebo-Controlled, Randomized Trial. Circulation. 2020 Jul 28;142(4):419-421. doi: 10.1161/CIRCULATIONAHA.120.046320. Epub 2020 Jul 27. No abstract available.

  PMID: 32718248 BACKGROUND

• Raber L, Ueki Y, Otsuka T, Losdat S, Haner JD, Lonborg J, Fahrni G, Iglesias JF, van Geuns RJ, Ondracek AS, Radu Juul Jensen MD, Zanchin C, Stortecky S, Spirk D, Siontis GCM, Saleh L, Matter CM, Daemen J, Mach F, Heg D, Windecker S, Engstrom T, Lang IM, Koskinas KC; PACMAN-AMI collaborators. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022 May 10;327(18):1771-1781. doi: 10.1001/jama.2022.5218.

  PMID: 35368058 BACKGROUND

• Kim BJ, Kim JS. Ischemic stroke subtype classification: an asian viewpoint. J Stroke. 2014 Jan;16(1):8-17. doi: 10.5853/jos.2014.16.1.8. Epub 2014 Jan 31.

  PMID: 24741560 BACKGROUND

• Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, Janis LS, Lutsep HL, Barnwell SL, Waters MF, Hoh BL, Hourihane JM, Levy EI, Alexandrov AV, Harrigan MR, Chiu D, Klucznik RP, Clark JM, McDougall CG, Johnson MD, Pride GL Jr, Torbey MT, Zaidat OO, Rumboldt Z, Cloft HJ; SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011 Sep 15;365(11):993-1003. doi: 10.1056/NEJMoa1105335. Epub 2011 Sep 7.

  PMID: 21899409 BACKGROUND

• Hong KS, Bang OY, Park JH, Jung JM, Lee SH, Song TJ, Nam HS, Park HK, Jung KH, Heo SH, Koo J, Yu KH, Park KY, Kim CK, Park HK, Lee J, Lee J, Seo WK. Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial. J Stroke. 2023 May;25(2):242-250. doi: 10.5853/jos.2022.02957. Epub 2023 Apr 11.

  PMID: 37032475 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Interventions

alirocumab

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Single center study, Registry based, Pragmatic, Prospective trial

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: October 16, 2023
• Study Start: October 15, 2023
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): November 15, 2026
• Last Updated: October 16, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)