Clinical trial NCT04128475: Observational Study of Cardiovascular Disease.
Official title: Long-term Study of LDL-c Lowering With Evolocumab: Observational Follow-up After the FOURIER OUTCOMES Trial.
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Cardiovascular Diseases
Cardiovascular Morbidity
Coronary Heart Disease
Low-density-lipoprotein-type
Keywords: Cardiovascular events
Coronary heart disease
Cardiovascular death
Low density lipoprotein cholesterol (LDL-c)
Evolocumab
FOURIER OUTCOMES
Lead sponsor: University of Sydney
Sponsor class: OTHER
Collaborators: name: The TIMI Study Group
name: Imperial College London
name: University of Oslo
name: Amgen
First posted: 2019-10-16
Enrollment: 1137
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants in selected countries who completed the FOURIER OUTCOMES trial, irrespective of non-fatal on-study events during FOURIER OUTCOMES trial, and who agree to take part in the FOURIER LEGACY study following study completion will be enrolled into this trial.

Brief summary: This observational study will follow participants who completed follow-up in the FOURIER OUTCOMES trial to evaluate the long-term effects of evolocumab treatment. Long-term post-trial (legacy) beneficial effects have been reported with statins, niacin, hypoglycemic therapy and fibrates. Whether similar effects are seen after LDL cholesterol (LDL-c) lowering by PCSK9 inhibition is currently unknown.

Evolocumab therapy causes a profound reduction in LDL cholesterol of approximately 60%. Statins have shown legacy effects over 5 years post-trial, including a 7% reduction in total mortality in meta-analysis and 12% reduction in coronary mortality. It would therefore be hypothesized that additional effects beyond the trial period would be conferred by previous evolocumab treatment. It is also important to assess the long-term safety of prior evolocumab treatment.


Eligibility criteria: Subjects who completed the FOURIER OUTCOMES trial (defined as attendance at close-out visit irrespective of treatment compliance) will be approached by FOURIER OUTCOMES site investigators and asked about their interest in taking part in this trial.

Primary outcomes:
measure: To evaluate the potential long-term effect of evolocumab treatment on a composite of CV death, MI, stroke or coronary revascularisation in participants completing participation in the FOURIER OUTCOMES trial.
timeFrame: 5 years
Secondary outcomes:
measure: To evaluate the potential long-term effect of evolocumab treatment on a composite of CV death, MI, stroke or coronary revascularization in patients completing participation in the FOURIER OUTCOMES trial.
timeFrame: 5 years
measure: To evaluate the long-term effect of evolocumab treatment on CV death.
timeFrame: 5 years
measure: To evaluate the long-term effects of evolocumab treatment on CHD death.
timeFrame: 5 years
measure: To evaluate the long-term effect of evolocumab treatment on the individual components of the primary endpoint and any other CV hospitalizations.
timeFrame: 5 years
measure: To evaluate the long-term effect of evolocumab treatment on amputations and peripheral revascularization.
timeFrame: 5 years
measure: To evaluate the long-term effect of evolocumab treatment in terms of all-cause death (and non-CV, including cancer, death).
timeFrame: 5 years
measure: To assess the effect modification of use or prescription lipid-lowering treatment classes (statins, cholesterol absorption inhibitors, PCSK9i) administered at FOURIER OUTCOMES trial entry on the outcomes above.
timeFrame: 5 years
measure: To assess the effect modification by baseline characteristics on defined study outcomes above.
timeFrame: 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: TIMI Study Group
state: Massachusetts
city: Nydalen
country: Norway
facility: Oslo University Hospital
state: Oslo
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: National Health and Medical Research Council, Australia
name: Anthony Keech
role: STUDY_CHAIR
affiliation: Imperial College London
name: Peter Sever
role: STUDY_CHAIR
References: