Effect of Evolocumab on Vascular Function

NCT03626831 | Completed Phase 4 DMC

• 1 other identifier: CRC2017EVO
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase IV, randomized (1:1), prospective, double-blind, placebo controlled, parallel-group, single center study at the Clinical Research Unit (CRC) of the Department of Nephrology and Hypertension, with its two separate locations:

• Nürnberg, Kreuzburger Str. 2, 90471 Nürnberg, and
• Erlangen, Ulmenweg 18, 91054 Erlangen The results of this study provide strong support for the concept that it is lower LDL-C levels that is key to achieving better outcomes, and that it is possible to achieve these on top of statin therapy (despite the much debated potential "pleiotropic" effects of statins). At least 65 patients will be randomized (1:1) and included (informed consent) in order to obtain 58 fully evaluable subjects (29 with evolocumab, 29 with placebo). Patients will be simultaneously recruited from investigator's outpatient clinics, referring physicians, and advertisement in local newspapers, and social media. Those patients that appear to potentially fulfill the inclusion criteria will be invited to a screening visit. After providing informed consent, patients will be tested for inclusion/exclusion criteria and for feasibility of vascular measurements (in particular to ensure that adequate imaging of the brachial artery is possible). Patients will provide a blood sample for laboratory testing. If the patient then fulfills inclusion criteria and in the absence of exclusion criteria, the patient will be enrolled into the trial, and the study visits will be scheduled. Randomization will take place at the latest one day prior to the study visit 2 (e.g. at the latest at visit 2a). At visit 2, baseline vascular function parameters will be obtained and the patient will be given an SC injection of the study drug (either SC 420 mg evolocumab or SC placebo). At visit 4, the second injection of study drug will be administered. After 1, 4 and 8 weeks of treatment (visits 3, 4 and 5), testing of vascular function will be repeated. At visit 6, a final close out visits will be performed to gather additional safety information.

Conditions

Atherosclerotic Cardiovascular Disease

Keywords

CVD; LDL; heart failure; PCSK9

Outcome Measures

Primary Outcomes (1)

• Percent change of FMD

  Percent change of FMD (UNEX EF) after 8 weeks of treatment from baseline

  8 weeks

Secondary Outcomes (5)

• Absolute change of FMD (UNEX EF)

  8 weeks

• Absolute change of L-FMC

  8 weeks

• Percent change of L-FMC

  8 weeks

• Absolute change of combined FMD+L-FMC (UNEX EF)

  8 weeks

• Percent change of combined FMD+L-FMC (UNEX EF)

  8 weeks

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Baseline vascular function parameters will be obtained and the patient will be given an SC injection of the study drug by Evolocumab Prefilled Syringe (1x SC 420 mg evolocumab).

Drug: Evolocumab Prefilled Syringe

Placebo

PLACEBO COMPARATOR

Baseline vascular function parameters will be obtained and the patient will be given an SC injection of Placebos (1x SC Placebo).

Drug: Placebos

Interventions

Evolocumab Prefilled Syringe DRUG

Injection of study drug

Treatment

Placebos DRUG

Injection of placebo

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent in written form
• Male or female 40 - 80 years
• History of clinically evident atherosclerotic cardiovascular disease as evidenced by ANY of the following:
• diagnosis of coronary artery disease as evidenced by acute coronary syndrome, myocardial infarction (MI), coronary stent implantation, coronary stenosis ≥50% by coronary angiography
• diagnosis of non-hemorrhagic stroke or transient ischemic attack (TIA)
• symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) \< 0.85, or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease, or artery stenosis ≥50% by angiography
• Fasting LDL-C ≥ 70 mg/dL (≥ 1.8 mmol/L) or non-HDL-C ≥ 100 mg/dL (≥ 2.6mmol/L) on optimized background lipid lowering therapy (please see Appendix 14.3.)
• Stable background lipid lowering therapy for at least 4 weeks (please see Appendix 14.3)
• Most recent fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L) by central laboratory before randomization

You may not qualify if:

• Inability to image the brachial artery and to perform FMD
• Subjects with statin intolerance
• Known or suspected homozygous familial hypercholesterolemia (FH)
• Subject must not be randomized within 4 weeks of their most recent MI or stroke
• NYHA class III or IV, or last known left ventricular ejection fraction \< 30%
• Atrial fibrillation
• Known hemorrhagic stroke at any time
• Uncontrolled or recurrent ventricular tachycardia
• Planned or expected cardiac surgery or revascularization within 3 months after randomization
• Uncontrolled hypertension defined as sitting pSBP \> 180 mmHg or pDBP \> 110 mmHg
• Use of cholesteryl ester transfer protein (CETP) inhibition treatment, mipomersen, or lomitapide within 12 months prior to randomization. Fenofibrate therapy must be stable for at least 6 weeks prior to final screening at a dose that is appropriate for the duration of the study in the judgment of the investigator. Other fibrate therapy (and derivatives) are prohibited
• Prior use of PCSK9 inhibition treatment other than evolocumab or use of evolocumab \< 12 weeks prior to final lipid screening
• Untreated or inadequately treated hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) \< lower limit of normal (LLN) or \> 1.5 times the upper limit of normal (ULN), respectively, and free thyroxine (T4) levels that are outside normal range at final screening
• Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2 at final screening
• Active liver disease or hepatic dysfunction, defined as serum Glutamate-Oxaloacetate-Transaminase (SGOT) or serum Glutamate-Pyruvate-Transaminase (SGPT)\> 3 times the ULN as determined by central laboratory analysis at final screening

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

Clinical Research Center, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg

Erlangen, 91054, Germany

Location

Related Publications (1)

• Gunes-Altan M, Bosch A, Striepe K, Schiffer M, Achenbach S, Schmieder RE, Kannenkeril D. Endothelial function in high-risk patients with ezetimibe therapy. J Clin Lipidol. 2025 Sep-Oct;19(5):1364-1373. doi: 10.1016/j.jacl.2025.07.001. Epub 2025 Jul 9.

  PMID: 40813220 DERIVED

MeSH Terms

Conditions

Atherosclerosis; Heart Failure

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Study Officials

• Roland E Schmieder, MD

  University Hospital Erlangen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Medicine

Model Details: randomized (1:1), prospective, double-blind, placebo controlled, parallel-group

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 13, 2018
• Study Start: April 4, 2019
• Primary Completion: April 15, 2021
• Study Completion: July 12, 2021
• Last Updated: July 11, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)