Design and rationale of the EBBINGHAUS trial

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8 March 2017

Design and rationale of the EBBINGHAUS trial

The Journal Clinical Cardiology has published on the design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo controlled, multicenter study to assess the effect of the human anti-PCSK9 monoclonal antibody evolocumab on cognitive function in patients with clinically evident cardiovascular disease receiving statin background lipid-lowering therapy1.

Observational studies of lipid-lowering drugs have raised concerns about statins causing memory impairments leading to a warning from the US FDA in 2012. Similar questions have been raised regarding other lipid lowering drugs and neurocognitive function, including proprotein convertase subtilisin/kexin-type 9 inhibitors (PCSK9i).

Clinical Cardiology has published on the design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo controlled, multicenter study to assess the effect of the human anti-PCSK9 monoclonal antibody evolocumab on cognitive function in patients with clinically evident cardiovascular disease receiving statin background lipid-lowering therapy1.

The EBBINGHAUS trial (ClinicalTrials.gov Identifier: NCT02207634) was conducted in 1,974 patients participating in the FOURIER trial (ClinicalTrials.gov Identifier: NCT01764633), a 27,564 patient study assessing the impact of additional LDL-Cholesterol reduction on major cardiovascular events when evolocumab is used in combination with statin therapy.

For EBBINGHAUS, cognitive testing was performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline, weeks 24 and 48, every 48 weeks thereafter, and at study end. The primary endpoint was the spatial working memory strategy index of executive function (SWMsi). The primary hypothesis was that evolocumab would be noninferior to placebo in the mean change from baseline over time in SWMsi. Secondary objectives include comparisons between randomized treatment groups in: working memory as assessed by the CANTAB Spatial Working Memory (SWM) test between-errors score, memory function as assessed by the CANTAB Paired Associates Learning (PAL) test and psychomotor speed as assessed by the CANTAB Reaction Time (RTI) test.   An exploratory analysis will compare neurocognitive function in patients with post-baseline low-density lipoprotein cholesterol <25 mg/dL.

Full results from the FOURIER and EBBINGHAUS trials will be presented at the American College of Cardiology 66th Annual Scientific Session between the 17th and 19th March, 2017:

Evolocumab FOURIER outcomes trial:
Late-Breaking Clinical Trials session
Friday, March 17 at 9 a.m. ET.

Evolocumab EBBINGHAUS cognitive function trial:
Late-Breaking Clinical Trials session
Saturday, March 18 at 9 a.m. ET.

Kenton Zavitz PhD, Director of Clinical Affairs at Cambridge Cognition will be in attendance at the ACC conference in Washington DC; book a meeting with Kenton to discuss the use of CANTAB in Clinical Trials. 

For more information about CANTAB cognitive assessment tools to evaluate drug safety and efficacy, please see our clinical trials section.


Reference:

1 Giugliano, R., Mach, F., Zavitz, K., Kurtz, C., Schneider, J., & Wang, H. et al. (2017). Design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin backgroun. Clinical Cardiology. doi:10.1002/clc.22678

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