Coronary Artery DiseasePhase 4CHORALNCT04073134
The CHORAL Flow Study
A Phase 4 study testing Evolocumab in people with Coronary Artery Disease and Atherosclerosis, run by Imperial College London at 1 site in United Kingdom.
Trial summary
CHORAL Flow is a randomised, double blinded, placebo-controlled trial of the effects of evolocumab on coronary flow at 12 weeks. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Disease, Atherosclerosis, Hyperlipidemias
- What is being tested?
- Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Sep 2019to 27 May 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College NHS Foundation Trust
London, W12 0HS
About this study
Official title: 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.
Read the 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.
- Conditions
- Coronary Artery Disease, Atherosclerosis, Hyperlipidemias
- Being tested
- Evolocumab, Placebo
- Keywords
- Coronary Artery Disease, Atherosclerosis
- Medical subject headings
- Coronary Artery Disease, Atherosclerosis, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabBiological
Also called Repatha, AMG 145
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
PlaceboDrug
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab | Active comparator | Participants will receive evolocumab 140 mg subcutaneous injections once every 2 weeks. Receives: Biological: Evolocumab |
| Placebo | Placebo comparator | Participants will receive placebo subcutaneous injections once every 2 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal coronary flow velocity changes from baseline to 12 weeks
Measured invasively using a doppler sensor tipped wire
Measured: Measured at baseline and after 12 weeks of therapy
Secondary outcomes (4)
Coronary Flow Reserve (CFR), measured invasively
Measured: Measured at baseline and after 12 weeks of therapy
Hyperaemic Microvascular Resistance, measured invasively
Measured: Measured at baseline and after 12 weeks of therapy
Maximal coronary flow (non-invasive) measured non-invasively using ultrasound (echo)
Measured: 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: Measured at baseline and after 12 weeks of therapy and in single-blinded extended treatment arm at 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2019
- Study start11 Sep 2019
- Primary completion27 Mar 2022
- Study completion27 May 2022
Why it stopped: Funding withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised control Trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ricardo Petraco, PhD, Principal investigator, Imperial College LondonHenry Seligman, MBBS, Study director, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04073134
- Sponsor's protocol ID
- 18HH4626
- Other IDs
- 2018-002483-11, 2018
- Acronym
- CHORAL
- Status last verified
- Aug 2024
- First submitted
- 27 Aug 2019
- Last updated
- 6 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholesterol Reduction With Evolocumab and Coronary MicrovascuLar Function and Coronary Flow: The CHORAL Flow Study
- ClinicalTrials.gov ID
- NCT04073134
- Acronym / sponsor ID
- CHORAL / 18HH4626
- Conditions
- Coronary Artery Disease, Atherosclerosis, Hyperlipidemias
- Keywords
- Coronary Artery Disease, Atherosclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding withdrawn
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 11 Sep 2019 (actual)
- Primary completion
- 27 Mar 2022 (actual)
- Study completion
- 27 May 2022 (actual)
- First posted
- 29 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
CHORAL Flow is a randomised, double blinded, placebo-controlled trial of the effects of evolocumab on coronary flow at 12 weeks.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised control Trial
| Arm | Type | Receives |
|---|---|---|
| Evolocumab | Active comparator | Biological: EvolocumabParticipants will receive evolocumab 140 mg subcutaneous injections once every 2 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo subcutaneous injections once every 2 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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%;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvolocumabAlso: Repatha, AMG 145Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen. | Biological | Evolocumab |
| PlaceboAdministered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen. | Drug | Placebo |
Primary outcome
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
4 secondary outcomes
Coronary Flow Reserve (CFR), measured invasively
Time frame: 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
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
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
Results and safety
The study was stopped early (reason given: Funding withdrawn). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ricardo Petraco, PhD principal investigator
Imperial College London
Henry Seligman, MBBS study director
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Evolocumab in people with Coronary Artery Disease and Atherosclerosis, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Funding withdrawn). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal coronary flow velocity changes from baseline to 12 weeks (time frame: Measured at baseline and after 12 weeks of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024; AzTrials last refreshed its copy on 2 Nov 2026.