NCT04659525

Brief Summary

Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol, reducing in turn the risk of cardiovascular events. Whether evolcumab is effective in haemodialized patients is uncertain. The investigators will conduct a randomized, double-blind, placebo-controlled trial to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab in high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia. Patients will be randomly assigned to receive evolocumab (140 mg subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) or matching placebo (subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) for 24 weeks. The primary efficacy end point will be the proportion of patients that will reduce LDL-C \< 55 mg/dL in the evolocumab group compared to placebo at 24 weeks. The key secondary efficacy end points will be: the reduction of LDL-C from baseline at 4, 6 and 12 weeks; the reduction of HDL-C, non-HDL cholesterol and triglycerides from baseline at 24 weeks. Every adverse event (serious and non-serious) correlated to drug infusion will be recorded (safety end-point).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Nov 2020

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2020

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

December 2, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

December 9, 2020

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2021

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2021

Completed
Last Updated

December 17, 2020

Status Verified

December 1, 2020

Enrollment Period

1.1 years

First QC Date

December 2, 2020

Last Update Submit

December 13, 2020

Conditions

HypercholesterolemiaCKD Stage 5Chronic Kidney Disease Requiring Chronic Dialysis

Keywords

HypercholesterolemiaChronic DialysisStatin intollerant patientsLDL reductionCardiovascular risk

Outcome Measures

Primary Outcomes (1)

  • LDL cholesterol change dichotomic

    proportion of patients that achieve an LDL cholesterol level \< 55 mg/dL

    24 weeks

Secondary Outcomes (4)

  • LDL cholesterol change time-points

    4 weeks, 12 weeks, 24 weeks

  • HDL cholesterol change

    24 weeks

  • non-HDL cholesterol change

    24 weeks

  • Triglycerides change

    24 weeks

Study Arms (2)

Evolocumab + Ezetimibe

EXPERIMENTAL

Patients in this arm will receive subcutaneous evolocumab 140 mg every two weeks plus ezetimibe 10 mg per os daily for 24 weeks

Drug: EvolocumabDrug: Ezetimibe

Placebo + Ezetimibe

PLACEBO COMPARATOR

Patients in this arm will receive subcutaneous placebo every two weeks plus ezetimibe 10 mg per os daily for 24 weeks

Drug: EzetimibeDrug: Placebo

Interventions

EvolocumabDRUG

In the intervention arm evolocumab 140 mg subcutaneous every 2 weeks will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia

Evolocumab + Ezetimibe
EzetimibeDRUG

Ezetimibe 10 mg daily will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia in both the placebo arm (plus placebo) and in the intervention arm (plus evolocumab)

Evolocumab + EzetimibePlacebo + Ezetimibe
PlaceboDRUG

In the placebo arm placebo subcutaneous every 2 weeks will be administered for 24 weeks to high cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia

Placebo + Ezetimibe

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • high cardiovascular risk defined as patients with: Documented cardiovascular disease (CVD), clinical or unequivocal on imaging. Documented clinical CVD includes previous acute myocardial infarction, coronary revascularization and other arterial revascularization procedures, stroke and TIA, aortic aneurysm and PAD. Unequivocally documented CVD on imaging includes plaque on coronary angiography or carotid ultrasound; DM with target organ damage or with a major risk factor such as smoking or marked hypercholesterolaemia or marked hypertension.
  • History of statin intolerance, demonstrated by: trial of ≥2 statins with intolerance of any dose or to increase statin dose above the total maximum doses because of intolerable: Myopathy or myalgia (muscle pain, ache, or weakness without CK elevation), or Myositis (muscle symptoms with increased CK levels), or Rhabdomyolysis (muscle symptoms with marked CK elevation) and Resolution or improvement of symptoms when the statin dose was decreased or discontinued
  • patients with LDL-C \>55 mg/dL
  • end-stage renal disease on chronic hemodialysis
  • Participant is willing and able to give informed consent for participation in the study.

You may not qualify if:

  • secondary hypercholesterolemia (i.e. hypothyroidism, Primary biliary cholangitis, etc)
  • Use of drugs or dietary supplements that can impact on cholesterol value (i.e. progestinic, red yeast rice, niacin \>200 mg/d, lipid-regulating drugs - eg, fibrates or derivatives, ezetimibe, bile-acid sequestrants, stanols, or stanol esters - )
  • Previous treatment with evolocumab or any other anti-PCSK9 therapy
  • Inability to provide informed consent or to attend follow-up visits
  • Unreliability as a study participant based on judgment of investigator's knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, psychosis)
  • Current enrollment in another investigational device or drug study or \<30 d since ending another investigational device or drug study
  • serum triglycerides level \> 400 mg/dL at baseline
  • Pregnancy, breastfeeding, or inadequate birth control in premenopausal female subjects
  • Laboratory values at screening CK \>3 × ULN; AST or ALT \>2 × ULN

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Policlinico Casilino

Rome, 00169, Italy

RECRUITING

Related Publications (7)

  • 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: 31504418BACKGROUND

  • Wanner C, Krane V, Marz W, Olschewski M, Mann JF, Ruf G, Ritz E; German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005 Jul 21;353(3):238-48. doi: 10.1056/NEJMoa043545.

    PMID: 16034009BACKGROUND

  • Fellstrom BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, Chae DW, Chevaile A, Cobbe SM, Gronhagen-Riska C, De Lima JJ, Lins R, Mayer G, McMahon AW, Parving HH, Remuzzi G, Samuelsson O, Sonkodi S, Sci D, Suleymanlar G, Tsakiris D, Tesar V, Todorov V, Wiecek A, Wuthrich RP, Gottlow M, Johnsson E, Zannad F; AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009 Apr 2;360(14):1395-407. doi: 10.1056/NEJMoa0810177. Epub 2009 Mar 30.

    PMID: 19332456BACKGROUND

  • Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellstrom B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Gronhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R; SHARP Investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011 Jun 25;377(9784):2181-92. doi: 10.1016/S0140-6736(11)60739-3. Epub 2011 Jun 12.

    PMID: 21663949BACKGROUND

  • Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.

    PMID: 24694531BACKGROUND

  • 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: 30403574BACKGROUND

  • 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: 28304224BACKGROUND

MeSH Terms

Conditions

HypercholesterolemiaRenal Insufficiency, Chronic

Interventions

evolocumabEzetimibe

Condition Hierarchy (Ancestors)

HyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesRenal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Central Study Contacts

Gennaro Cice, MD

CONTACT

0039330915294gennarocice@hormail.com

Leonardo Calò, MD

CONTACT

0623188406leonardocalo.doc@gmail.com

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head of Cardiology Department

Study Record Dates

First Submitted

December 2, 2020

First Posted

December 9, 2020

Study Start

November 1, 2020

Primary Completion

November 30, 2021

Study Completion

December 30, 2021

Last Updated

December 17, 2020

Record last verified: 2020-12

Locations

IT(1)