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The CHORAL Flow Study (CHORAL)

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ClinicalTrials.gov Identifier: NCT04073134
Recruitment Status : Not yet recruiting
First Posted : August 29, 2019
Last Update Posted : August 29, 2019
Sponsor:
Information provided by (Responsible Party):
Imperial College London

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

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Atherosclerosis Hyperlipidemias Biological: Evolocumab Drug: Placebo Phase 4

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised control Trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cholesterol Reduction With Evolocumab and Coronary MicrovascuLar Function and Coronary Flow: The CHORAL Flow Study
Estimated Study Start Date : August 27, 2019
Estimated Primary Completion Date : March 27, 2022
Estimated Study Completion Date : May 27, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arm Intervention/treatment
Active Comparator: Evolocumab
Participants will receive evolocumab 140 mg subcutaneous injections once every 2 weeks.
Biological: Evolocumab
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
Other Names:
  • Repatha
  • AMG 145

Placebo Comparator: Placebo
Participants will receive placebo subcutaneous injections once every 2 weeks.
Drug: Placebo
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.




Primary Outcome Measures :
  1. Maximal coronary flow velocity changes from baseline to 12 weeks [ Time Frame: Measured at baseline and after 12 weeks of therapy ]
    Measured invasively using a doppler sensor tipped wire


Secondary Outcome Measures :
  1. Coronary Flow Reserve (CFR), measured invasively [ Time Frame: Measured at baseline and after 12 weeks of therapy ]
  2. Hyperaemic Microvascular Resistance, measured invasively [ Time Frame: Measured at baseline and after 12 weeks of therapy ]
  3. Maximal coronary flow (non-invasive) measured non-invasively using ultrasound (echo) [ Time Frame: Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks ]
  4. Coronary Flow Reserve (CFR) (Non-invasive) measured non-invasively using ultrasound (echo) [ Time Frame: Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks ]

Other Outcome Measures:
  1. Coronary wave intensity analysis derived from invasive pressure and flow measurements [ Time Frame: Measured at baseline and after 12 weeks of therapy ]
    Exploratory outcome

  2. Exercise coronary flow reserve (CFR) (Non-invasive) measured non-invasively using ultrasound (echo). [ Time Frame: Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks ]
    Exploratory outcome



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04073134


Contacts
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Contact: Ricardo Petraco, PhD 020 7594 5735 imperial.choralstudy@nhs.net
Contact: Henry Seligman, MBBS 020 7594 5735 h.seligman@nhs.net

Locations
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United Kingdom
Imperial College NHS Foundation Trust
London, United Kingdom, W12 0HS
Sponsors and Collaborators
Imperial College London
Investigators
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Principal Investigator: Ricardo Petraco, PhD Imperial College London
Study Director: Henry Seligman, MBBS Imperial College London

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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT04073134     History of Changes
Other Study ID Numbers: 18HH4626
2018-002483-11 ( EudraCT Number )
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Imperial College London:
Coronary Artery Disease
Atherosclerosis
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Atherosclerosis
Hyperlipidemias
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Evolocumab
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs