Clinical trial NCT02114541: Correlation Between Coronary and Carotid Atherosclerotic Disease and Links With Clinical Outcomes
Official title: Global Observational Study to Evaluate the Correlation Between Coronary and Carotid Atherosclerotic Disease (CAD) and Links With Clinical Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Vascular Disease
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
First posted: 2014-04-15
Enrollment: 1339
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects who were scheduled for clinically-indicated coronary angiography and undergone baseline coronary angiography and IVUS imaging data along with baseline carotid ultrasound imaging.

Brief summary: The relationship of the natural history of atherosclerosis between different vascular beds has not been well characterized. Determination and comparison of the relative rates of progression and extents of atherosclerosis in the coronary and carotid arterial trees may have major impacts on clinical research and clinical practice. Correlation between findings in the carotid and coronary circulations is an important scientific and clinical topic to address. Results from a well design study incorporating imaging technologies that currently represent the gold standards for the assessment of coronary and carotid artery plaque burden, will have potentially impact on clinical research and clinical practice.

Detailed description: The CAIN-003 study was a prospective observational multi-center imaging study of subjects scheduled for clinically-indicated coronary angiography. CAIN-003 provided for the collection of baseline coronary angiography and IVUS imaging data along with baseline carotid ultrasound imaging. CAIN-003 study participants underwent follow-up coronary and carotid imaging at 2-years, and were then contacted by phone on an annual basis for an additional 3 years for the collection of cardiovascular and cerebrovascular clinical endpoints.

MHICC-31052012 was a prospective, observational, multi-center study of subjects who had successfully undergone baseline imaging in the dal-PLAQUE 2 study (A multicenter, double-blind, randomized, placebo-controlled study, evaluating the effect of treatment with dalcetrapib 600 mg on atherosclerosis disease). The dal-PLAQUE 2 study, which provided for the collection of baseline and 2-year follow-up coronary angiography, coronary IVUS and carotid ultrasound imaging data, was terminated by the sponsor prior to completion due to the discontinuation of the dalcetrapib drug development program. The MHICC-31052012 study allowed for the collection of follow-up imaging and clinical endpoint data from subjects who had successfully undergone baseline IVUS imaging in dal-PLAQUE 2.

Data from CAIN-003 and MHICC-31052012 was pooled to support the objective of determining the correlation and clinical relevance of these imaging endpoints.

The objectives of the CAIN-003 and MHICC-31052012 study were:

* To compare the extent of atherosclerosis present in the coronary vasculature with the extent of atherosclerosis present in the carotid vasculature at a single point in time.
* To compare the associations of atherosclerosis burden with coronary risk factors in the coronary arteries and carotid arteries, in multivariable regression.
* To compare the rate of atherosclerosis progression or regression in the coronary vasculature with the rate of atherosclerosis progression or regression in the carotid vasculature over a 2-year period.
* To determine the correlation between imaging biomarkers and cardiovascular outcomes over a 5-year period.

Eligibility criteria: Inclusion Criteria:

1. Male and female patients over the age of 18 years.
2. Patients scheduled for clinically indicated coronary angiography and possible ad hoc percutaneous coronary intervention (PCI) will be evaluated before their scheduled procedure.
3. Written informed consent (approved by the Institutional Review Board \[IRB\]/Independent Ethics Committee \[IEC\]) obtained prior to any study specific procedures.
4. Patients considered to be stable at enrollment (at the discretion of the investigator) are eligible provided they meet all other entry criteria.
5. Angiographic inclusion criteria:

   * Entire Coronary Circulation: The patient must have angiographic evidence of coronary artery disease as defined by at least one lesion in any of the three major native coronary arteries that has \>20% reduction in lumen diameter by angiographic visual estimation or prior history of PCI. This vessel does not need to be the target coronary artery for IVUS. Any vessel with previous PCI may not be used as the target coronary artery.
   * Left Main Coronary Artery: The patient must not have \> 50% reduction in lumen diameter by visual angiographic estimation.
   * Target Coronary Artery: Patient will be required to have one "target" coronary artery for IVUS that has not undergone prior PCI, that is not a candidate to undergo PCI presently or in the next 24 months, and that has not been the cause of a recent myocardial infarction. The proximal 4 cm of the "target" artery in which

IVUS examination will be performed at baseline:

* Must have a diameter stenosis \< 50% lumen diameter by visual assessment of the angiogram;
* Must have a reference diameter \> 2.5 mm;
* Must be free of filling defects suggestive of thrombus;
* Must not present any anatomical characteristic (such as but not limited to severe tortuosity or calcification) that would impede IVUS interrogation at baseline or follow-up
* Note: a lesion of up to 60% stenosis is permitted, distal to the target segment. A side branch of the target coronary artery for IVUS may not be a target for PCI.

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

1. Women of childbearing potential (women who are not surgically sterile or postmenopausal defined as amenorrhea for \>12 months) who refuse to undergo a urine or serum pregnancy test immediately prior to baseline and repeat imaging evaluations The urine or serum pregnancy test must be negative prior to imaging evaluations.
2. Previous coronary artery bypass graft (CABG) surgery or probable need for CABG in the next 24 months.
3. Patients who have symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] Class III or IV) at baseline.
4. Patients with clinically significant valvular heart disease likely to require surgical repair or replacement during the treatment period of the study
5. Any clinically significant medical condition or presence of any laboratory abnormality that is considered by the investigator to be clinically important and could interfere with the conduct of the study.
6. The presence of severe liver disease as defined by the presence of cirrhosis, chronic active hepatitis, or chronic jaundice with hyperbilirubinemia,
7. Patients with eGFR \< 45 ml/min prior to baseline imaging procedures, or with nephrotic syndrome
8. Patients with a life expectancy less than 2 years.
9. History of malignancy (except for curatively treated basal cell or squamous cell carcinoma of the skin) during the 3 years prior to the screening.
10. Unable or unwilling to comply with protocol requirements, or deemed by the investigator to be unfit for the study.

Primary outcomes:
measure: Nominal change at follow-up from baseline in percent atheroma volume (PAV) obtained using intravascular ultrasound (IVUS)
timeFrame: Participants will have a baseline IVUS and a two year follow-up IVUS
Secondary outcomes:
measure: plaque volume in target coronary artery
timeFrame: change at 2 year follow-up from baseline
measure: change in plaque volume in the 5-mm sub-segment of target coronary artery
timeFrame: change at 2 year follow-up from baseline
measure: Total vessel volume in the target coronary artery
timeFrame: change at final 2 year follow-up from baseline
measure: change in coronary score assessed by quantitative coronary angiography
timeFrame: change at final 2 year follow-up from baseline
measure: nominal change in carotid IMT(CIMT)
timeFrame: change at final 2 year follow-up from baseline
Other outcomes:
measure: clinical endpoints
timeFrame: up to five year follow-up
Locations:
city: Los Angeles
country: United States
facility: University of southern California
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor
state: California
city: Fort Lauderdale
country: United States
facility: Jim Moran Heart and Vascular Research Institute, Holy Cross Hospital
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Florida Cardiovascular Research
state: Florida
city: Decatur
country: United States
facility: Emory University VA Medical Center
state: Georgia
city: Louisville
country: United States
facility: Norton Heart Specialist Springs
state: Kentucky
city: Columbia
country: United States
facility: John Hopkins University Office Capitol Region Research-CAPRES
state: Maryland
city: Midland
country: United States
facility: CV Research at MidMichigan Medical Center Midland
state: Michigan
city: Muskegon
country: United States
facility: Mercy Health Partners
state: Michigan
city: Petoskey
country: United States
facility: Cardiac and Vascular Research Center of Northern Michigan
state: Michigan
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital
state: North Carolina
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Oak Ridge
country: United States
facility: Parkway Cardiology associates
state: Tennessee
city: Dallas
country: United States
facility: Dalla VAMC
state: Texas
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Mazankowski Alberta Heart Institute University Of Alberta Hospital ABACUS
state: Alberta
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Interventional Cardiology Research, St. Paul's Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria Heart Institute Foundation (Office)/Royal Jubilee Hospital
state: British Columbia
city: Saint John's
country: Canada
facility: Eastern Regional Health Authority
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Queen Elizabeth II - Health Sciences Centre
state: Nova Scotia
city: Cambridge
country: Canada
facility: Cambridge Cardiac Care
state: Ontario
city: Hamilton
country: Canada
facility: McMaster Clinic Hamilton General Hospital
state: Ontario
city: Kitchener
country: Canada
facility: KMH Cardiology & Diagnostics Centre
state: Ontario
city: London
country: Canada
facility: University Hospital/LHSC
state: Ontario
city: Mississauga
country: Canada
facility: KMH Cardiology & Diagnostics Centre
state: Ontario
city: Newmarket
country: Canada
facility: York PCI Research
state: Ontario
city: Oshawa
country: Canada
facility: Heart Care Research
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Civic Hospital / University of Ottawa Heart Institute
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Cardiology Research
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Chicoutimi
country: Canada
facility: Complexe Hospitalier de la Sagamie
state: Quebec
city: Fleurimont
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Gatineau
country: Canada
facility: CSSS-Hopital de Gatineau, secteur Hull
state: Quebec
city: Gatineau
country: Canada
facility: Q & T Research
state: Quebec
city: Greenfield Park
country: Canada
facility: Viacar Recherche Clinique
state: Quebec
city: Laval
country: Canada
facility: Cite de la Sante
state: Quebec
city: Longueuil
country: Canada
facility: CDRC Rive Sud
state: Quebec
city: Longueuil
country: Canada
facility: Foothills Medical Centre
state: Quebec
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montréal
country: Canada
facility: CHUM - Hopital Hotel-Dieu
state: Quebec
city: Montréal
country: Canada
facility: CUSM Montreal General Hospital
state: Quebec
city: Montréal
country: Canada
facility: Hopital Sacré-Cœur de Montreal
state: Quebec
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec
state: Quebec
city: Saint-Charles-Borromée
country: Canada
facility: Centre Hospitalier Régional de Lanaudière
state: Quebec
city: Saint-Georges
country: Canada
facility: Centre de santé et des services sociaux de Beauce
state: Quebec
city: Saint-Jérôme
country: Canada
facility: St-Jerome Medical Research Inc.
state: Quebec
city: Toronto
country: Canada
facility: Sunnybrook Health Science Center
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre de santé et de services sociaux de Trois-Rivières
state: Quebec
city: Val D'Or
country: Canada
facility: CSSS Vallée de l'Or
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Calgary
country: Canada
facility: Foothills Medical Centre
city: Aachen
country: Germany
facility: Universitatsklinikum Aachen
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Heidelberg
country: Germany
facility: Universitat Heidelberg
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Elblag
country: Poland
facility: Wojewodzki Szpital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Oddzial Kliniczny Choroby
city: Lublin
country: Poland
facility: Samodzielny Publiczny
city: Poznan
country: Poland
facility: Szpital Kliniczny
city: Warszawa
country: Poland
facility: Klinika Kardiologii
city: Warszawa
country: Poland
facility: Instytut Kardiologii
city: Wroclaw
country: Poland
facility: Woskowy Szpital Kliniczny
city: Geneve
country: Switzerland
facility: Hopitaux Universitaire de Genève
Study officials:
affiliation: Montreal Heart Institute
name: Jean-Claude Tardif, M.D
role: PRINCIPAL_INVESTIGATOR
References: