The CHORAL Flow Study (CHORAL)

August 5, 2024 updated by: Imperial College London

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
      • London, United Kingdom, W12 0HS
        • Imperial College NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Measured at baseline and after 12 weeks of therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Coronary Flow Reserve (CFR), measured invasively
Time Frame: Measured at baseline and after 12 weeks of therapy
Measured at baseline and after 12 weeks of therapy
Hyperaemic Microvascular Resistance, measured invasively
Time Frame: Measured at baseline and after 12 weeks of therapy
Measured at baseline and after 12 weeks of therapy
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
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)
Time Frame: Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks
Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Coronary wave intensity analysis derived from invasive pressure and flow measurements
Time Frame: Measured at baseline and after 12 weeks of therapy
Exploratory outcome
Measured at baseline and after 12 weeks of therapy
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
Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Imperial College London

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ricardo Petraco, PhD, Imperial College London
  • Study Director: Henry Seligman, MBBS, Imperial College London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 11, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 27, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 27, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 27, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 29, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 18HH4626
  • 2018-002483-11 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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