The CHORAL Flow Study

Coronary Artery Disease Clinical Trial

— CHORAL  

Official title:

Cholesterol Reduction With Evolocumab and Coronary MicrovascuLar Function and Coronary Flow: The CHORAL Flow Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04073134
• Other study ID #: 18HH4626
• Secondary ID: 2018-002483-11
• Status: Terminated
• Phase: Phase 4
• Start date: September 11, 2019
• Est. completion date: May 27, 2022

Study information

• Verified date: March 2023
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CHORAL Flow is a randomised, double blinded, placebo-controlled trial of the effects of evolocumab on coronary flow at 12 weeks.

Description:

Evolocumab is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor which has been shown in the Fourier Trial to reduce major cardiovascular events in statin-treated patients with raised LDL cholesterol compared to placebo. The precise mechanisms via which evolocumab therapy impacts cardiovascular outcomes remain unknown. Coronary blood flow is a powerful predictor of clinical outcomes across a wide range of cardio-circulatory disorders as well as within normal subjects. Improvement in coronary microvascular function and coronary flow, therefore, could potentially represent one of the core pathways via which evolocumab offers cardiovascular protection. In the CHORAL Flow Study patients will undergo invasive and non-invasive physiological assessment with coronary flow measurements before and after 12 weeks of therapy with evolocumab or placebo. Patients in the treatment arm will go on to have a further non-invasive assessment of coronary flow at 24 weeks of therapy in a single blinded fashion.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: May 27, 2022
• Est. primary completion date: March 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Patients aged between 18 and 80 years, with a clinical indication for coronary angiography and:

1. willing to provide consent: Provide written (signed and dated) informed consent and be capable of understanding the study and co-operating with treatment and follow-up.

2. raised levels of fasting (>9h) LDL-cholesterol (=2mmol/L) either on optimal statin therapy (90% of overall sample) or intolerants to statins (restricted to 10% of overall sample). Optimal statin therapy will be defined as at least 4 weeks of atorvastatin 40mg or more, with no change in statin dose during this period.

3. at least one other risk factor for vascular disease or established vascular disease.

4. willing and able to use a highly effective method of contraception from screening until 15 weeks after the last dose of IP if a woman of childbearing potential.

Exclusion Criteria:

1. Patients unable or unwilling to provide written informed consent;

2. Patients unable to undergo cardiac catheterisation;

3. Patients with contraindication to adenosine (severe asthma, second or third degree atrioventricular block, heart rate lower than 40/min at rest, previous formal diagnosis of long QT syndrome, acute decompensated heart failure, severe hypotension, advanced (stage IV) or decompensated chronic obstructive pulmonary disease (COPD);

4. Uncontrolled hypertension (systolic BP >180mmHg or DBP >110mmHg, despite ongoing therapy);

5. Clinical heart failure NYHA class III/IV or Ejection Fraction on imaging modality (Echo, MRI) <40%;

6. Severe valvular heart disease;

7. Severe (>95% diameter) epicardial coronary stenosis;

8. Recent (last 12 months) clinically significant cerebrovascular event (including ischaemic or haemorrhagic events);

9. End-stage renal failure (eGFR < 30 mL/min/1.73m2);

10. Advanced liver disease, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x ULN

11. Current use of PCSK9 inhibitor;

12. Malignancy with life expectancy <1y;

13. Currently or within last 3 months enrolled on another CTIMP;

14. Known allergy to evolocumab or incipients;

15. Women of childbearing potential who are unwilling or unable to use a highly effective method of contraception from screening until 15 weeks after the last dose of IP.

16. Subject is pregnant or breast feeding or planning to become pregnant or to breastfeed during screening, during treatment with IP and/ or within 15 weeks after the end of treatment with IP.

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Hyperlipidemias
• Myocardial Ischemia

Intervention

Biological:
• Evolocumab
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.

Drug:
• Placebo
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.

Locations

Country	Name	City	State
United Kingdom	Imperial College NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Coronary wave intensity analysis derived from invasive pressure and flow measurements	Exploratory outcome	Measured at baseline and after 12 weeks of therapy
Other	Exercise coronary flow reserve (CFR) (Non-invasive) measured non-invasively using ultrasound (echo).	Exploratory outcome	Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks
Primary	Maximal coronary flow velocity changes from baseline to 12 weeks	Measured invasively using a doppler sensor tipped wire	Measured at baseline and after 12 weeks of therapy
Secondary	Coronary Flow Reserve (CFR), measured invasively		Measured at baseline and after 12 weeks of therapy
Secondary	Hyperaemic Microvascular Resistance, measured invasively		Measured at baseline and after 12 weeks of therapy
Secondary	Maximal coronary flow (non-invasive) measured non-invasively using ultrasound (echo)		Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks
Secondary	Coronary Flow Reserve (CFR) (Non-invasive) measured non-invasively using ultrasound (echo)		Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks