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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01975376




Registration number
NCT01975376
Ethics application status
Date submitted
21/10/2013
Date registered
3/11/2013
Date last updated
11/07/2018

Titles & IDs
Public title
The Evaluation of Bococizumab (PF-04950615;RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects
Scientific title
Phase 3 Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel Group Evaluation Of The Efficacy, Safety, And Tolerability Of Bococizumab (Pf-04950615) In Reducing The Occurrence Of Major Cardiovascular Events In High Risk Subjects.
Secondary ID [1] 0 0
CV OUTCOMES 1
Secondary ID [2] 0 0
B1481022
Universal Trial Number (UTN)
Trial acronym
SPIRE-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular Disease 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - bococizumab (PF-04950615)
Treatment: Drugs - Placebo

Experimental: bococizumab (PF-04950615) - 150 mg, every 2 weeks, subcutaneous

Placebo comparator: Placebo - Placebo comparator, every 2 weeks, subcutaneous.


Treatment: Drugs: bococizumab (PF-04950615)
150 mg, every 2 weeks, subcutaneous. The duration of the treatment period will depend upon reaching the targeted number of adjudicated and confirmed CV outcome events, approximately 3 to 4 years after the entry of first subject into the study.

Treatment: Drugs: Placebo
Placebo comparator, every 2 weeks, subcutaneous. The duration of the treatment period will depend upon reaching the targeted number of adjudicated and confirmed CV outcome events, approximately 3 to 4 years after the entry of first subject into the study.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Major Cardiovascular (CV) Event
Timepoint [1] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.4 years)
Secondary outcome [1] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infraction, or Non-Fatal Stroke
Timepoint [1] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of the CV death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years)
Secondary outcome [2] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infraction, Non-Fatal Stroke, or Hospitalization for Unstable Angina Needing Urgent Revascularization
Timepoint [2] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI, non-fatal stroke, or hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years)
Secondary outcome [3] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infarction, or Non-Fatal Stroke
Timepoint [3] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of the all-cause death, non-fatal MI, or non-fatal stroke (maximum duration: up to 3.4 years)
Secondary outcome [4] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization
Timepoint [4] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years)
Secondary outcome [5] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke and Hospitalization for Unstable Angina
Timepoint [5] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of cardiovascular death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina (maximum duration: up to 3.4 years)
Secondary outcome [6] 0 0
Event Rate Per 100 Participant-Years For Cardiovascular Death
Timepoint [6] 0 0
From baseline until the date of adjudicated and confirmed occurrence of cardiovascular death (maximum duration: up to 3.4 years)
Secondary outcome [7] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Any Myocardial Infarction (Fatal or Non-Fatal)
Timepoint [7] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of any MI (fatal or non-fatal) (maximum duration: up to 3.4 years)
Secondary outcome [8] 0 0
Event Rate Per 100 Participant-Years For Fatal Myocardial Infarction
Timepoint [8] 0 0
From baseline until the date of adjudicated and confirmed occurrence of fatal MI (maximum duration: up to 3.4 years)
Secondary outcome [9] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Non-Fatal Myocardial Infarction
Timepoint [9] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of non-fatal MI (maximum duration: up to 3.4 years)
Secondary outcome [10] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Any Stroke (Fatal or Non-Fatal)
Timepoint [10] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) (maximum duration: up to 3.4 years)
Secondary outcome [11] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Any Stroke (Fatal or Non-Fatal), of Any Etiology
Timepoint [11] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal), of any etiology (maximum duration: up to 3.4 years)
Secondary outcome [12] 0 0
Event Rate Per 100 Participant-Years For Fatal Stroke
Timepoint [12] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of fatal stroke (maximum duration: up to 3.4 years)
Secondary outcome [13] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Non-Fatal Stroke
Timepoint [13] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of non-fatal stroke (maximum duration: up to 3.4 years)
Secondary outcome [14] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Hospitalization for Unstable Angina
Timepoint [14] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina (maximum duration: up to 3.4 years)
Secondary outcome [15] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Hospitalization for Congestive Heart Failure (CHF)
Timepoint [15] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for congestive heart failure (maximum duration: up to 3.4 years)
Secondary outcome [16] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Coronary Revascularization
Timepoint [16] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of coronary revascularization (maximum duration: up to 3.4 years)
Secondary outcome [17] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Coronary Artery Bypass Graft Surgery (CABG)
Timepoint [17] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of CABG (maximum duration: up to 3.4 years)
Secondary outcome [18] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Percutaneous Coronary Intervention (PCI)
Timepoint [18] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of PCI (maximum duration: up to 3.4 years)
Secondary outcome [19] 0 0
Event Rate Per 100 Participant-Years For First Occurrence of Any Arterial Revascularizations
Timepoint [19] 0 0
From baseline until the date of first adjudicated and confirmed occurrence of any arterial revascularizations (maximum duration: up to 3.4 years)
Secondary outcome [20] 0 0
Event Rate Per 100 Participant-Years For All-Cause Death
Timepoint [20] 0 0
From baseline until the date of adjudicated and confirmed occurrence of all-cause death (maximum duration: up to 3.4 years)
Secondary outcome [21] 0 0
Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14
Timepoint [21] 0 0
Baseline, Week 14
Secondary outcome [22] 0 0
Nominal Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14
Timepoint [22] 0 0
Baseline, Week 14
Secondary outcome [23] 0 0
Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Last Post-Baseline Measurement
Timepoint [23] 0 0
Baseline, last post-baseline measurement (any time up to Week 140)
Secondary outcome [24] 0 0
Percent Change From Baseline in Lipid Levels at Week 14
Timepoint [24] 0 0
Baseline, Week 14
Secondary outcome [25] 0 0
Percent Change From Baseline in Log-Transformed Lipoprotein (a) (Lp[a]) and Triglycerides at Week 14
Timepoint [25] 0 0
Baseline, Week 14
Secondary outcome [26] 0 0
Percent Change From Baseline in Log-Transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14
Timepoint [26] 0 0
Baseline, Week 14

Eligibility
Key inclusion criteria
* Must be on background lipid lowering treatment.
* Must be at high risk of a CV event.
* Must have an LDL C >/=70 mg/dL (1.8 mmol/L) or non-HDL-C >/= 100 mg/dL (2.6 mmol/L).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Planned coronary (PCI or CABG) or other arterial revascularization.
* New York Heart Association Class IV congestive heart failure or left ventricular ejection fraction < 25% by cardiac imaging.
* Chronic renal insufficiency with creatinine clearance of <30 ml/min/1.73m^2 by MDRD formula or with end state renal disease on dialysis.
* History of hemorrhagic stroke.
* Prior exposure to bococizumab or other investigational PCSK9 inhibitor.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/03/2017
Sample size
Target
Accrual to date
Final
16784
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders - Camperdown
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 0 0
Central Coast Neurosciences Research - Erina
Recruitment hospital [5] 0 0
Gosford Hospital - Gosford
Recruitment hospital [6] 0 0
Australian Clinical Research Network - Maroubra
Recruitment hospital [7] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [8] 0 0
Holy Spirit Northside Private Hospital Limited - Chermside
Recruitment hospital [9] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [10] 0 0
Core Research Group Pty Ltd - Milton
Recruitment hospital [11] 0 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [12] 0 0
Austrials Pty Ltd - Sherwood
Recruitment hospital [13] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [14] 0 0
Adelaide Medical Research - Ashford
Recruitment hospital [15] 0 0
SA Heart - Ashford
Recruitment hospital [16] 0 0
Southern Adelaide Diabetes and Endocrine Service - Daws Park
Recruitment hospital [17] 0 0
Department of Cardiology, Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [18] 0 0
Heart and Vascular Research - Fullarton
Recruitment hospital [19] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [20] 0 0
Eastern Health - Box Hill Hospital - Box Hill
Recruitment hospital [21] 0 0
The Northern Hospital - Epping
Recruitment hospital [22] 0 0
Barwon Health-The Geelong Hospital - Geelong
Recruitment hospital [23] 0 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment hospital [24] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [25] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [26] 0 0
Fremantle Hospital - Fremantle
Recruitment hospital [27] 0 0
HPS Pharmacies - Joondalup
Recruitment hospital [28] 0 0
Joondalup Cardiovascular Trials Foundation Inc. - Joondalup
Recruitment hospital [29] 0 0
Sir Charles Gairdner Hospital, Heart Research Institute - Nedlands
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2250 - Erina
Recruitment postcode(s) [4] 0 0
2250 - Gosford
Recruitment postcode(s) [5] 0 0
2035 - Maroubra
Recruitment postcode(s) [6] 0 0
2065 - St Leonards
Recruitment postcode(s) [7] 0 0
4032 - Chermside
Recruitment postcode(s) [8] 0 0
4029 - Herston
Recruitment postcode(s) [9] 0 0
4064 - Milton
Recruitment postcode(s) [10] 0 0
4020 - Redcliffe
Recruitment postcode(s) [11] 0 0
4075 - Sherwood
Recruitment postcode(s) [12] 0 0
4215 - Southport
Recruitment postcode(s) [13] 0 0
5035 - Ashford
Recruitment postcode(s) [14] 0 0
5041 - Daws Park
Recruitment postcode(s) [15] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [16] 0 0
5063 - Fullarton
Recruitment postcode(s) [17] 0 0
7250 - Launceston
Recruitment postcode(s) [18] 0 0
3128 - Box Hill
Recruitment postcode(s) [19] 0 0
3076 - Epping
Recruitment postcode(s) [20] 0 0
3220 - Geelong
Recruitment postcode(s) [21] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [22] 0 0
3004 - Melbourne
Recruitment postcode(s) [23] 0 0
3050 - Parkville
Recruitment postcode(s) [24] 0 0
6160 - Fremantle
Recruitment postcode(s) [25] 0 0
6027 - Joondalup
Recruitment postcode(s) [26] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
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Alabama
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United States of America
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Alaska
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Arizona
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Arkansas
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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PCIA DE Tucuman
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Pcia. DE Santa FE
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Argentina
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Provincia DE Buenos Aires
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Argentina
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Argentina
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Santa FE
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De Pinte
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Gilly
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Hasselt
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Huy
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Liege
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Massemen
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Mons
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Overpelt
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Tienen
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Bahia
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BA
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Ceara
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CE
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Distrito Federal
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Espirito Santo
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Goias
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GO
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MG
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PE
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PR
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RJ
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RN
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RS
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SAO Paulo
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Brazil
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SP
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Sao Paulo
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Canada
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Alberta
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British Columbia
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Manitoba
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Ontario
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Quebec
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Metropolitana
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China
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Guangdong
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Heilongjiang
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Henan
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Hungary
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Hungary
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Hungary
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Hatvan
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Hungary
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Hungary
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Hungary
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Israel
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Israel
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Israel
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Israel
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Israel
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Israel
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Israel
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Israel
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Kfar Saba
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Israel
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Kfar-Saba
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Israel
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Nahariya
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Israel
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Israel
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Petach Tikva
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Israel
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Israel
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Raanana
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Israel
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Israel
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Israel
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Israel
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Israel
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Israel
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Korea, Republic of
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Korea, Republic of
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Korea, Republic of
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Mexico
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Netherlands
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York

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study evaluates the PCSK9 inhibitor, Bococizumab (PF-04950615;RN316), compared to placebo, in reducing the occurrence of major cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and unstable angina requiring urgent revascularization, in high risk subjects who are receiving background lipid lowering therapy and have cholesterol laboratory values of LDL-C \>/= 70 mg/dL (1.8 mmol/L) or non-HDL-C \>/= 100 mg /dL (2.6 mmol/L).
Trial website
https://clinicaltrials.gov/study/NCT01975376
Trial related presentations / publications
Chasman DI, Hyde CL, Giulianini F, Danning RD, Wang EQ, Hickling T, Ridker PM, Loomis AK. Genome-wide pharmacogenetics of anti-drug antibody response to bococizumab highlights key residues in HLA DRB1 and DQB1. Sci Rep. 2022 Mar 11;12(1):4266. doi: 10.1038/s41598-022-07997-5.
Pradhan AD, Aday AW, Rose LM, Ridker PM. Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy. Circulation. 2018 Jul 10;138(2):141-149. doi: 10.1161/CIRCULATIONAHA.118.034645. Epub 2018 May 1.
Ridker PM, Rose LM, Kastelein JJP, Santos RD, Wei C, Revkin J, Yunis C, Tardif JC, Shear CL; Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Investigators. Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: Results from the SPIRE randomized trials of bococizumab. J Clin Lipidol. 2018 Jul-Aug;12(4):958-965. doi: 10.1016/j.jacl.2018.03.088. Epub 2018 Apr 3.
Ridker PM, Revkin J, Amarenco P, Brunell R, Curto M, Civeira F, Flather M, Glynn RJ, Gregoire J, Jukema JW, Karpov Y, Kastelein JJP, Koenig W, Lorenzatti A, Manga P, Masiukiewicz U, Miller M, Mosterd A, Murin J, Nicolau JC, Nissen S, Ponikowski P, Santos RD, Schwartz PF, Soran H, White H, Wright RS, Vrablik M, Yunis C, Shear CL, Tardif JC; SPIRE Cardiovascular Outcome Investigators. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients. N Engl J Med. 2017 Apr 20;376(16):1527-1539. doi: 10.1056/NEJMoa1701488. Epub 2017 Mar 17.
Public notes

Contacts
Principal investigator
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Pfizer CT.gov Call Center
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Pfizer
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Contact person for public queries
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01975376