Study to Evaluate Changes in Cognitive Function in Patients Treated With PCSK9 Inhibitors

NCT04319081 | Completed

• 3 other identifiers: JSA-ALI-2019-012019/653PMID: 33941059
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 12

Brief Summary

The main objective will be to evaluate the changes in the cognitive function in naive patients treated with PCSK9 inhibitors (Alirocumab and Evolocumab) by using the Montreal Cognitive Assesment questionnaire (MOCA). The secondary objectives will be: 1) To evaluate the levels of LDL-cholesterol changes from the beginning to the end of the study 2) To evaluate changes in Quality of Life among the EuroQol EQ-5D-3L questionnaire (it will also be associated to the cognitive function) 3) Assesment of direct costs in medications and outpatients consultations related with the health procedures.

Conditions

Cognitive Function; Hypercholesterolemia; Quality of Life

Keywords

Cognitive Function; Hypercholesterolemia; Quality of Life; Pharmacoeconomics; PCSK9 inhibitors; Alirocumab; Evolocumab

Outcome Measures

Primary Outcomes (1)

• Changes in cognitive function

  Assesment by Montreal Cognitive Assessment questionnaire (MOCA). Minimum value is 0 and maximum value is 30. A higher or equal value to 26 points will be considered normal.

  24 to 36 months

Secondary Outcomes (3)

• LDL-cholesterol values

  24 to 36 months

• Changes in Quality of life

  24 to 36 months

• Direct costs

  24 to 36 months

Other Outcomes (3)

• Total Cholesterol

  24 to 36 months

• Lp(a)

  24 to 36 months

• Cost-effectiveness

  24 to 36 months

Study Arms (1)

Uncontrolled patients with hypercholesterolemia

Patients that meet criteria inclusions and they have just started to take Alirocumab or Evolocumab

Drug: PCSK9 inhibitor

Interventions

PCSK9 inhibitor DRUG

Patients are included after PCSK9 inhibitors prescription , at the first dispensation

Uncontrolled patients with hypercholesterolemia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with familial hypercholesterolemia (homozygous and heterozygous) and/or cardiovascular disease with LDL-cholestrol value \> 100 mg/dL and maximum statine doses or intolerance. With a first prescription of PCSK9 inhibitors

You may qualify if:

• Patients 18 years old or over
• To start with the first funded dose of PCSK9 inhibitors ( LDL \> 100 mg/dL)
• Maximum dose or statin intolerance

You may not qualify if:

• Diagnosis of any disease related with cognitive deterioration

Sponsors & Collaborators

• Jose Seijas Amigo: lead

Study Sites (12)

Hospital de Virxen da Xunqueira de Cee

Cee, A Coruña, Spain

Location

Hospital Arquiteto Marcide de Ferrol

Ferrol, A Coruña, Spain

Location

Hospital del Barbanza

Ribeira, A Coruña, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, A Coruña, Spain

Location

Hospital Público da Mariña de Burela

Burela de Cabo, Lugo, Spain

Location

Hospital de Monforte

Monforte de Lemos, Lugo, Spain

Location

Hospital do Barco de Valdeorras

O Barco de Valdeorras, Ourense, Spain

Location

Hospital Alvaro Cunqueiro de Vigo

Vigo, Pontevedra, Spain

Location

Complejo Hospitalario Universitario de A Coruña

A Coruña, 15706, Spain

Location

Hospital Lucus-Augusti de Lugo

Lugo, Spain

Location

Complejo Hospitalario Universitario de Ourense

Ourense, Spain

Location

Complexo Hospitalario Universitario de Pontevedra

Pontevedra, Spain

Location

Related Publications (14)

• Giugliano RP, Mach F, Zavitz K, Kurtz C, Im K, Kanevsky E, Schneider J, Wang H, Keech A, Pedersen TR, Sabatine MS, Sever PS, Robinson JG, Honarpour N, Wasserman SM, Ott BR; EBBINGHAUS Investigators. Cognitive Function in a Randomized Trial of Evolocumab. N Engl J Med. 2017 Aug 17;377(7):633-643. doi: 10.1056/NEJMoa1701131.

  PMID: 28813214 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

• Kolodziejczak M, Navarese EP. Role of PCSK9 antibodies in cardiovascular disease: Critical considerations of mortality and neurocognitive findings from the current literature. Atherosclerosis. 2016 Apr;247:189-92. doi: 10.1016/j.atherosclerosis.2016.02.011. Epub 2016 Feb 15.

  PMID: 26926598 BACKGROUND

• Lipinski MJ, Benedetto U, Escarcega RO, Biondi-Zoccai G, Lhermusier T, Baker NC, Torguson R, Brewer HB Jr, Waksman R. The impact of proprotein convertase subtilisin-kexin type 9 serine protease inhibitors on lipid levels and outcomes in patients with primary hypercholesterolaemia: a network meta-analysis. Eur Heart J. 2016 Feb 7;37(6):536-45. doi: 10.1093/eurheartj/ehv563. Epub 2015 Nov 17.

  PMID: 26578202 BACKGROUND

• Shibata N, Ohnuma T, Higashi S, Higashi M, Usui C, Ohkubo T, Watanabe T, Kawashima R, Kitajima A, Ueki A, Nagao M, Arai H. No genetic association between PCSK9 polymorphisms and Alzheimer's disease and plasma cholesterol level in Japanese patients. Psychiatr Genet. 2005 Dec;15(4):239. doi: 10.1097/00041444-200512000-00004. No abstract available.

  PMID: 16314752 BACKGROUND

• Xue-Shan Z, Juan P, Qi W, Zhong R, Li-Hong P, Zhi-Han T, Zhi-Sheng J, Gui-Xue W, Lu-Shan L. Imbalanced cholesterol metabolism in Alzheimer's disease. Clin Chim Acta. 2016 May 1;456:107-114. doi: 10.1016/j.cca.2016.02.024. Epub 2016 Mar 2.

  PMID: 26944571 BACKGROUND

• Banach M, Rizzo M, Nikolic D, Howard G, Howard V, Mikhailidis D. Intensive LDL-cholesterol lowering therapy and neurocognitive function. Pharmacol Ther. 2017 Feb;170:181-191. doi: 10.1016/j.pharmthera.2016.11.001. Epub 2016 Nov 16.

  PMID: 27865998 BACKGROUND

• Paquette M, Saavedra YGL, Poirier J, Theroux L, Dea D, Baass A, Dufour R. Loss-of-Function PCSK9 Mutations Are Not Associated With Alzheimer Disease. J Geriatr Psychiatry Neurol. 2018 Mar;31(2):90-96. doi: 10.1177/0891988718764330. Epub 2018 Mar 21.

  PMID: 29562810 BACKGROUND

• Robinson JG, Rosenson RS, Farnier M, Chaudhari U, Sasiela WJ, Merlet L, Miller K, Kastelein JJ. Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab: Pooled Data From Randomized Trials. J Am Coll Cardiol. 2017 Feb 7;69(5):471-482. doi: 10.1016/j.jacc.2016.11.037.

  PMID: 28153102 BACKGROUND

• Seijas-Amigo J, Rodriguez-Penas D, Estany-Gestal A, Suarez-Artime P, Santamaria-Cadavid M, Gonzalez-Juanatey JR. Observational multicentre prospective study to assess changes in cognitive function in patients treated with PCSK9i. Study protocol. Farm Hosp. 2021 Mar 5;45(3):150-154. doi: 10.7399/fh.11569.

  PMID: 33941059 BACKGROUND

• Seijas-Amigo J, Gayoso-Rey M, Mauriz-Montero MJ, Suarez-Artime P, Casas-Martinez A, Dominguez-Guerra M, Gonzalez-Freire L, Estany-Gestal A, Codero-Fort A, Rodriguez-Manero M, Gonzalez-Juanatey JR; e investigadores MEMOGAL. Impact of the COVID-19 pandemic in the lipid control of the patients that start PCSK9 inhibitors. Clin Investig Arterioscler. 2022 Sep-Oct;34(5):245-252. doi: 10.1016/j.arteri.2022.01.003. Epub 2022 Feb 3. English, Spanish.

  PMID: 35287972 BACKGROUND

• Seijas-Amigo J, Mauriz-Montero MJ, Suarez-Artime P, Gayoso-Rey M, Reyes-Santias F, Estany-Gestal A, Casas-Martinez A, Gonzalez-Freire L, Rodriguez-Vazquez A, Perez-Rodriguez N, Villaverde-Pineiro L, Castro-Rubinos C, Espino-Paisan E, Cordova-Arevalo O, Rodriguez-Penas D, Cardeso-Paredes B, Ribeiro-Ferreiro M, Rodriguez-Manero M, Cordero A, Gonzalez-Juanatey JR, Memogal Investigators. Cost-Utility Analysis of PCSK9 Inhibitors and Quality of Life: A Two-Year Multicenter Non-Randomized Study. Diseases. 2024 Oct 5;12(10):244. doi: 10.3390/diseases12100244.

  PMID: 39452487 DERIVED

• Seijas-Amigo J, Mauriz-Montero MJ, Suarez-Artime P, Gayoso-Rey M, Estany-Gestal A, Casas-Martinez A, Gonzalez-Freire L, Rodriguez-Vazquez A, Perez-Rodriguez N, Villaverde-Pineiro L, Castro-Rubinos C, Espino-Faisan E, Rodriguez-Manero M, Cordero A, Gonzalez-Juanatey JR; Investigadores MEMOGAL. Cognitive Function with PCSK9 Inhibitors: A 24-Month Follow-Up Observational Prospective Study in the Real World-MEMOGAL Study. Am J Cardiovasc Drugs. 2023 Sep;23(5):583-593. doi: 10.1007/s40256-023-00604-6. Epub 2023 Aug 23.

  PMID: 37612529 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Pharmacist

Study Record Dates

• First Submitted: March 20, 2020
• First Posted: March 24, 2020
• Study Start: March 1, 2020
• Primary Completion: December 31, 2022
• Study Completion: January 13, 2023
• Last Updated: January 17, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

ES (12)