Heart Failure With Reduced Ejection FractionPhase 2EVO-HFNCT03791593
EVOlocumab in Stable Heart Failure With Reduced Ejection Fraction of Ischemic Etiology: EVO-HF Pilot
A Phase 2 study testing Evolocumab in people with Heart Failure With Reduced Ejection Fraction, run by Fundació Institut Germans Trias i Pujol at 3 sites in Spain.
Trial summary
Evolocumab has been able to reduce the incidence of cardiovascular events in patients that had at least one cardiovascular risk factor [28]. In patients with chronic HFrEF, as we mentioned before, treatment with statins is not recommended as it has not shown benefits in improving its prognosis. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction
- What is being tested?
- Evolocumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 3 sitesSpain
- Study dates
- 3 Dec 2018to 20 Jul 2022
- Phase
- Phase 2
- 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
- Signing of the informed consent
- Patient ≥18 years and ≤80 years of age
- LVEF <40%
- Ischemic etiology (evidence of at least one acute coronary event and/or CAD by coronary angiography or multi slice CT)
- New York Heart Association (NYHA) class II
- NT-proBNP ≥ 400 pg/mL
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- Hs-TnT >10 pg/mL
- LDL ≥ 70 mg/dL
- Stable CAD (last ACS before the last 3 months)
- GDMT according to 2016 ESC HF guidelines for at least the last 3 months.
- Statin treatment, whichever dose the patient receives at the time of enrolment, stable for at least 1 month, without need to statin uptitration.
Who cannot join
- Extracardiac disease with estimated life expectancy less than 1 year
- Contraindication to receiving evolocumab
- Hypersensitivity to the active substance or to any of the excipients
- Female subject who has not used an acceptable method of birth control for at least 1 month prior to screening and/or is not willing to inform her partner of her participation in this clinical trial and to use an acceptable method of effective birth control during treatment with evolocumab and for an additional 15 weeks after the end of treatment with evolocumab, unless the female subject is permanently sterilized or postmenopausal:
- A female is considered of childbearing potential unless permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal with menopause defined as:
- Age ≥55 years and ≥12 months of spontaneous and continuous amenorrhea, or
Show all 17Show fewer
- Age <55 years but no spontaneous menses for ≥2 years, or
- Age <55 years and spontaneous menses within the past 1 year, but currently amenorrheic, AND with follicle-stimulating hormone (FSH) levels >40 IU/L or estradiol levels <5 ng/dL or according to the definition of "postmenopausal range" for the laboratory involved.
- Patient <18 or ≥ 81 years
- Liver dysfunction (AST or ALT> 3 times the upper limit of normal value).
- Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73m²) or renal replacement therapy at screening (CKD-EPI equation).
- Coronary revascularization in the 3 months prior to randomization or pending coronary revascularization.
- Previous haemorrhagic stroke
- Uncontrolled hypertension (systolic blood pressure ≥ 140 or/and diastolic blood pressure ≥ 90 mmHg) either on or off therapy at screening or at baseline
- Uncontrolled hypothyroidism or hyperthyroidism
- Type 1 diabetes; newly diagnosed or poorly controlled type 2 diabetes (HbA1c > 8.5%)
- Uncontrolled cardiac arrhythmia
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Clínico de Valencia
Valencia, 46010
About this study
Evolocumab has been able to reduce the incidence of cardiovascular events in patients that had at least one cardiovascular risk factor [28]. In patients with chronic HFrEF, as we mentioned before, treatment with statins is not recommended as it has not shown benefits in improving its prognosis. However, CAD control stands as an approach that could improve the course of the disease by preventing microlesions that further weaken the heart. A recent multicenter study, the BIOSTAT-CHF [3436], was performed to determine whether the PCSK9-LDLR axis could predict risk in patients with HF. A multivariate analysis, which included BIOSTAT risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality and the composite endpoint (death or HF-related hospitalization). A similar analysis for LDLR revealed a negative association with mortality and the composite endpoint. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.
There is an unmet clinical need: blockade of the neurohormonal activation has provided advances in patients with HFrEF, yet mortality and morbidity remain unacceptably high. Approaching a strict control of lipid levels and CAD with evolocumab in stable HFrEF of ischemic ethology may represent a complementary pathophysiological pathway to reduce mortality and morbidity. The burden of CAD provides a solid rationale for testing the value of evolocumab in HF patients.
Read more
Therefore, a pilot trial is proposed to evaluate the beneficial effect of evolocumab by surrogate biological markers before considering an event analysis study.
Evolocumab reduces the risk of cardiovascular events in patients with established atherosclerotic disease, so this drug could play a role in HFrEF of ischemic etiology, by limiting macro- and micro-vascular coronary disease progression. In HFrEF patients due to ischemic etiology, there is a continuous troponin release due to persistent myocyte injury, which has been associated with adverse outcomes. Our hypothesis is that evolocumab may have the potential to reduce circulating hs-TnT levels, as a surrogate of myocyte injury due to atheroma progression in HFrEF. A positive result in this EVO-HF Pilot study may lead to the set-up of a large-scale multicenter prospective and randomized events study analyzing the role of lipid-lowering treatment by means of evolocumab in HFrEF of ischemic etiology
Read the detailed description
Evolocumab has been able to reduce the incidence of cardiovascular events in patients that had at least one cardiovascular risk factor [28]. In patients with chronic HFrEF, as we mentioned before, treatment with statins is not recommended as it has not shown benefits in improving its prognosis. However, CAD control stands as an approach that could improve the course of the disease by preventing microlesions that further weaken the heart. A recent multicenter study, the BIOSTAT-CHF [3436], was performed to determine whether the PCSK9-LDLR axis could predict risk in patients with HF. A multivariate analysis, which included BIOSTAT risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality and the composite endpoint (death or HF-related hospitalization). A similar analysis for LDLR revealed a negative association with mortality and the composite endpoint. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.
There is an unmet clinical need: blockade of the neurohormonal activation has provided advances in patients with HFrEF, yet mortality and morbidity remain unacceptably high. Approaching a strict control of lipid levels and CAD with evolocumab in stable HFrEF of ischemic ethology may represent a complementary pathophysiological pathway to reduce mortality and morbidity. The burden of CAD provides a solid rationale for testing the value of evolocumab in HF patients.
Evolocumab reduces the risk of cardiovascular events in patients with established atherosclerotic disease, so this drug could play a role in HFrEF of ischemic etiology, by limiting macro- and micro-vascular coronary disease progression. In HFrEF patients due to ischemic etiology, there is a continuous troponin release due to persistent myocyte injury, which has been associated with adverse outcomes. Our hypothesis is that evolocumab may have the potential to reduce circulating hs-TnT levels, as a surrogate of myocyte injury due to atheroma progression in HFrEF. A positive result in this EVO-HF Pilot study may lead to the set-up of a large-scale multicenter prospective and randomized events study analyzing the role of lipid-lowering treatment by means of evolocumab in HFrEF of ischemic etiology.
Therefore, a pilot trial is proposed to evaluate the beneficial effect of evolocumab by surrogate biological markers before considering an event analysis study.
- Being tested
- Evolocumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
Also called Repatha
Evolocumab is a human IgG2 monoclonal antibody, it will add to patient treatment during 12 months.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | The patient will receive evolocumab 420 mg/month on top of guideline-driven medical treatment Receives: Drug: Evolocumab |
| Control group | No intervention | The patient will continue guideline-driven medical treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in hs-TnT levels at 1 year
Change of high-sensitivity troponin T (hs-TnT) levels from baseline to 1 year.
Measured: at 12 months of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2019
- Study start3 Dec 2018
- Primary completion30 Jun 2021
- Study completion20 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundació Institut Germans Trias i Pujol
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antoni Bayes-Genís, MD,PhD,FESC, Principal investigator, HUGTIP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03791593
- Sponsor's protocol ID
- ICOR-2016-05
- Other IDs
- 2017-004656-30, 2017
- Acronym
- EVO-HF
- Status last verified
- Feb 2023
- First submitted
- 30 Dec 2018
- Last updated
- 15 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EVOlocumab in Stable Heart Failure With Reduced Ejection Fraction of Ischemic Etiology: EVO-HF Pilot
- ClinicalTrials.gov ID
- NCT03791593
- Acronym / sponsor ID
- EVO-HF / ICOR-2016-05
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Fundació Institut Germans Trias i PujolUniversity, hospital or other
- Study start
- 3 Dec 2018 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 20 Jul 2022 (actual)
- First posted
- 2 Jan 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.
Evolocumab has been able to reduce the incidence of cardiovascular events in patients that had at least one cardiovascular risk factor [28]. In patients with chronic HFrEF, as we mentioned before, treatment with statins is not recommended as it has not shown benefits in improving its prognosis. However, CAD control stands as an approach that could improve the course of the disease by preventing microlesions that further weaken the heart. A recent multicenter study, the BIOSTAT-CHF [3436], was performed to determine whether the PCSK9-LDLR axis could predict risk in patients with HF. A multivariate analysis, which included BIOSTAT risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality and the composite endpoint (death or HF-related hospitalization). A similar analysis for LDLR revealed a negative association with mortality and the composite endpoint. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.
There is an unmet clinical need: blockade of the neurohormonal activation has provided advances in patients with HFrEF, yet mortality and morbidity remain unacceptably high. Approaching a strict control of lipid levels and CAD with evolocumab in stable HFrEF of ischemic ethology may represent a complementary pathophysiological pathway to reduce mortality and morbidity. The burden of CAD provides a solid rationale for testing the value of evolocumab in HF patients.
Therefore, a pilot trial is proposed to evaluate the beneficial effect of evolocumab by surrogate biological markers before considering an event analysis study.
Evolocumab reduces the risk of cardiovascular events in patients with established atherosclerotic disease, so this drug could play a role in HFrEF of ischemic etiology, by limiting macro- and micro-vascular coronary disease progression. In HFrEF patients due to ischemic etiology, there is a continuous troponin release due to persistent myocyte injury, which has been associated with adverse outcomes. Our hypothesis is that evolocumab may have the potential to reduce circulating hs-TnT levels, as a surrogate of myocyte injury due to atheroma progression in HFrEF. A positive result in this EVO-HF Pilot study may lead to the set-up of a large-scale multicenter prospective and randomized events study analyzing the role of lipid-lowering treatment by means of evolocumab in HFrEF of ischemic etiology
Detailed description
Evolocumab has been able to reduce the incidence of cardiovascular events in patients that had at least one cardiovascular risk factor [28]. In patients with chronic HFrEF, as we mentioned before, treatment with statins is not recommended as it has not shown benefits in improving its prognosis. However, CAD control stands as an approach that could improve the course of the disease by preventing microlesions that further weaken the heart. A recent multicenter study, the BIOSTAT-CHF [3436], was performed to determine whether the PCSK9-LDLR axis could predict risk in patients with HF. A multivariate analysis, which included BIOSTAT risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality and the composite endpoint (death or HF-related hospitalization). A similar analysis for LDLR revealed a negative association with mortality and the composite endpoint. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.
There is an unmet clinical need: blockade of the neurohormonal activation has provided advances in patients with HFrEF, yet mortality and morbidity remain unacceptably high. Approaching a strict control of lipid levels and CAD with evolocumab in stable HFrEF of ischemic ethology may represent a complementary pathophysiological pathway to reduce mortality and morbidity. The burden of CAD provides a solid rationale for testing the value of evolocumab in HF patients.
Evolocumab reduces the risk of cardiovascular events in patients with established atherosclerotic disease, so this drug could play a role in HFrEF of ischemic etiology, by limiting macro- and micro-vascular coronary disease progression. In HFrEF patients due to ischemic etiology, there is a continuous troponin release due to persistent myocyte injury, which has been associated with adverse outcomes. Our hypothesis is that evolocumab may have the potential to reduce circulating hs-TnT levels, as a surrogate of myocyte injury due to atheroma progression in HFrEF. A positive result in this EVO-HF Pilot study may lead to the set-up of a large-scale multicenter prospective and randomized events study analyzing the role of lipid-lowering treatment by means of evolocumab in HFrEF of ischemic etiology.
Therefore, a pilot trial is proposed to evaluate the beneficial effect of evolocumab by surrogate biological markers before considering an event analysis study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: EvolocumabThe patient will receive evolocumab 420 mg/month on top of guideline-driven medical treatment |
| Control group | No intervention | –The patient will continue guideline-driven medical treatment |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signing of the informed consent
- Patient ≥18 years and ≤80 years of age
- LVEF <40%
- Ischemic etiology (evidence of at least one acute coronary event and/or CAD by coronary angiography or multi slice CT)
- New York Heart Association (NYHA) class II
Key exclusion criteria (17 listed)
- Extracardiac disease with estimated life expectancy less than 1 year
- Contraindication to receiving evolocumab
- Hypersensitivity to the active substance or to any of the excipients
- Female subject who has not used an acceptable method of birth control for at least 1 month prior to screening and/or is not willing to inform her partner of her participation in this clinical trial and to use an acceptable method of effective birth control during treatment with evolocumab and for an additional 15 weeks after the end of treatment with evolocumab, unless the female subject is permanently sterilized or postmenopausal:
- A female is considered of childbearing potential unless permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal with menopause defined as:
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: RepathaEvolocumab is a human IgG2 monoclonal antibody, it will add to patient treatment during 12 months. | Drug | Experimental group |
Primary outcome
Change in hs-TnT levels at 1 year
Time frame: at 12 months of follow-up
Change of high-sensitivity troponin T (hs-TnT) levels from baseline to 1 year.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
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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.
Antoni Bayes-Genís, MD,PhD,FESC principal investigator
HUGTIP
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Evolocumab in people with Heart Failure With Reduced Ejection Fraction, run by Fundació Institut Germans Trias i Pujol at 3 sites in Spain.
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 11 inclusion and 17 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: finished, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in hs-TnT levels at 1 year (time frame: at 12 months of follow-up). 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 15 Feb 2023.