The CHORAL Flow Study

• Status: Recruiting
• Trial end date: 2022-05-27
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Imperial College London
• Treatments: Antibodies, Monoclonal; Evolocumab

Criteria

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.