Influence of Intensive Lipid-lowering on FFRCT (The FLOW-PROMOTE Study) (FlowPromote)

Influence of Intensive Lipid-lowering With Statin and Ezetimib Prescription on Computed Tomography Derived Fractional Flow Reserve in Patients With Stable Chest Pain (The FLOW-PROMOTE Study)

The FLOW-PROMOTE Study is an investigator-initiated, Danish multicenter study of patients with stable chest pain investigating whether lipid lowering is associated with recovery of impaired coronary flow as assessed by CT derived fractional flow reserve (FFRCT).

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Rosuvastatin 40mg

Detailed Description

Multicenter study (4 centers in Denmark), including 120 patients with stable chest pain and hemodynamically significant coronary artery disease as assessed by FFRCT. By using two lipid lowering treatment strategies ("usual" vs "intensive" care) over 18 months, the effect on coronary plaque regression and flow recovery are assessed from repeated CT angiograms with plaque and FFRCT analyses at 9 and 18 months.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bjarne L Noergaard, MD, PhD; Phone Number: +4540136570; Email: bnorgaard@dadlnet.dk
• Study Contact Backup: Name: Martin B Mortensen, MD, PhD; Phone Number: +4523882155; Email: martin.bodtker.mortensen@clin.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200 N
    • Recruiting
    • Aarhus University Hospital
    • Contact: Bjarne L Noergaard, MD, PhD; Phone Number: +4540136570; Email: bnorgaard@dadlnet.dk
    • Contact: Martin B Mortensen, MD, PhD; Phone Number: +4523882155; Email: martin.bodtker.mortensen@clin.au.dk
    • Sub-Investigator: Jesper M Jensen, MD, PhD
  • Esbjerg, Denmark, 6700
    • Recruiting
    • Southwestern Hospital Esbjerg
    • Contact: Niels-Peter R Sand, MD, PhD; Phone Number: +4528409148; Email: npsand@webspeed.dk
    • Contact: Lone D Kristensen, MD; Phone Number: +4521422813; Email: lone.dejbjerg@dadlnet.dk
  • Vejle, Denmark, 7100
    • Not yet recruiting
    • Lillebaelt Hospital
    • Contact: Martin Busk, MD, PhD; Phone Number: +4522473224; Email: martin.busk@rsyd.dk
    • Contact: Flemming H Steffensen, MD, PhD; Phone Number: +4551503862; Email: flemming.hald@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Symptoms suggestive of stable coronary artery disease (CAD)
2. No known CAD
3. At least one coronary stenosis with >49% lumen reduction determined by CT angiography
4. Sinus rhythm
5. At least one lesion with FFRCT <0.81 (see below)
6. Life expectancy >3 years
7. Fertile women must use safe contraception throughout the study period
8. Signed informed consent

5. LDL cholesterol >2.0 mM (patients already on lipid lowering medical therapy < 3 months can be included if meeting all of the above mentioned criteria)

Exclusion Criteria:

1. Unstable angina
2. Known CAD
3. Body mass index >40
4. Allergy to iodinated contrast media
5. Known statin intolerance
6. Poor coronary CT angiography image quality inadequate for FFRCT calculation (determined by core-laboratory)
7. Significant left main coronary artery (stenosis >49%) or three-vessel CAD determined by coronary CT angiography leading to direct referral to ICA
8. FFRCT <0.81 over the left main coronary artery or the proximal left anterior descendens artery (LAD) segment, or <0.76 over the mid-LAD, proximal circumflex, right coronary artery or intermediate coronary segments
9. Pregnancy (women with age >45 will be screened for pregnancy)
10. Moderate to severe liver failure
11. Estimated glomerular filtration rate (eGFR) < 60 ml/min
12. Participation in another trial
13. Does noes not wish to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: "Usual care"; "Usual care" prevention: atorvastatin 40 mg per day for 18 months	Drug: Rosuvastatin 40mg; Rosuvastatin 40 mg; Other Names: Ezetimib 10mg
Experimental: "Intensive care"; "Intensive care" prevention: rosuvastatin 40 mg + ezetimib 10 mg per day for 18 months	Drug: Rosuvastatin 40mg; Rosuvastatin 40 mg; Other Names: Ezetimib 10mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18-month change in coronary flow	Coronary flow will be assessed by repetitive FFRCT assessments (0,9 and 18 months)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18-month change high risk coronary plaque volumes	Will be assessed by measuring low attenuation coronary plaque (LAP) volumes at repetitive CT angiograms (0,9, and 18 months)	18 months
18-month change in high risk coronary plaque features	Will be assessed by quantifying the proportion of lesions with positive remodeling at repetitive CT angiograms (0,9, and 18 months).	18-months
18-month change in coronary vessel volumes	Will be assessed by calculating the vessel volume relative to myocardial mass (V/M) ratio determined from repetitive CT angiograms (0,9, and 18 months).	18-months
18-month change in indices of coronary inflammation	Will be assessed by the pericoronary fat attenuation index (FAI) determined from repetitive CT angiograms (0,9, and 18 months).	18-months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reproducibility assessment	There will be performed 2 CTA investigations at the 9 month follow-up. Reproducibility assessment of CT derived FFR, plaque markers, FAI and V/M ratio will be performed by calculation of standard error of measurement and within-subject coefficient of variation.	9-months

Collaborators and Investigators

• Sponsor: Bjarne Linde Noergaard
• Investigators: Principal Investigator: Bjarne L Noergaard, MD, PhD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2020
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: February 2, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Actual): February 5, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: coronary artery disease, fractional flow reserve
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: Aarhus University Hospital

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No