The CHORAL Flow Study

NCT04073134 | Terminated Phase 4 DMC

• 2 other identifiers: 18HH46262018-002483-11
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Coronary Artery Disease; Atherosclerosis; Hyperlipidemias

Keywords

Coronary Artery Disease; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Coronary Flow Reserve (CFR), measured invasively

  Measured at baseline and after 12 weeks of therapy

• Hyperaemic Microvascular Resistance, measured invasively

  Measured at baseline and after 12 weeks of therapy

• 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

• 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

Other Outcomes (2)

• Coronary wave intensity analysis derived from invasive pressure and flow measurements

  Measured at baseline and after 12 weeks of therapy

• Exercise 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

Study Arms (2)

Evolocumab

ACTIVE COMPARATOR

Participants will receive evolocumab 140 mg subcutaneous injections once every 2 weeks.

Biological: Evolocumab

Placebo

PLACEBO COMPARATOR

Participants will receive placebo subcutaneous injections once every 2 weeks.

Drug: Placebo

Interventions

Evolocumab BIOLOGICAL

Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.

Also known as: Repatha, AMG 145

Evolocumab

Placebo DRUG

Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged between 18 and 80 years, with a clinical indication for coronary angiography and:
• 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.
• 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.
• at least one other risk factor for vascular disease or established vascular disease.
• 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.

You may not qualify if:

• Patients unable or unwilling to provide written informed consent;
• Patients unable to undergo cardiac catheterisation;
• 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);
• Uncontrolled hypertension (systolic BP \>180mmHg or DBP \>110mmHg, despite ongoing therapy);
• Clinical heart failure NYHA class III/IV or Ejection Fraction on imaging modality (Echo, MRI) \<40%;
• Severe valvular heart disease;
• Severe (\>95% diameter) epicardial coronary stenosis;
• Recent (last 12 months) clinically significant cerebrovascular event (including ischaemic or haemorrhagic events);
• End-stage renal failure (eGFR \< 30 mL/min/1.73m2);
• Advanced liver disease, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3x ULN
• Current use of PCSK9 inhibitor;
• Malignancy with life expectancy \<1y;
• Currently or within last 3 months enrolled on another CTIMP;
• Known allergy to evolocumab or incipients;
• 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.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College NHS Foundation Trust

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Coronary Artery Disease; Atherosclerosis; Hyperlipidemias

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Ricardo Petraco, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

• Henry Seligman, MBBS

  Imperial College London

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised control Trial

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: August 29, 2019
• Study Start: September 11, 2019
• Primary Completion: March 27, 2022
• Study Completion: May 27, 2022
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)