Heart Failure With Preserved Ejection FractionNCT05826821
Biomarkers in HF: Circulating Biomarkers of Fibrosis and Cardiovascular Disease
An observational study of Heart Failure With Preserved Ejection Fraction, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Heart failure with preserved ejection fraction (HFpEF) represents one of the largest unmet needs in cardiovascular medicine. Heart muscle scarring (myocardial fibrosis) is a key HFpEF disease mechanism and represents an important therapeutic target. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Pirfenidone
- Type of treatment
- Pill or oral medicine
- How many people
- 107 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Mar 2017to 29 Apr 2020
- Phase
- Observational
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with heart failure with preserved ejection fraction and myocardial fibrosis
Who may be able to join
- Written informed consent.
- Male or female; aged 40 years or older.
- HF, defined as one symptom present at the time of screening, and one sign present at the time of screening or in the previous 12 months. Symptoms and signs are defined as:
- Symptoms: dyspnoea on exertion, orthopnoea or paroxysmal nocturnal dyspnoea Signs: peripheral oedema, crackles on chest auscultation post-cough, raised jugular venous pressure or chest x-ray demonstrating pleural effusion, pulmonary congestion, or cardiomegaly
- Left Ventricular Ejection Fraction (LVEF) > 45% at Visit 0, (any local LVEF measurement made using echocardiography or CMR).
- BNP ≥ 100 pg/ml or NTproBNP ≥ 300 pg/ml recorded at Visit 0. For patients in atrial fibrillation on Visit 0 ECG, BNP > 300pg/ml or NTproBNP > 900 pg/ml at Visit 0.
- Myocardial fibrosis, defined as Extracellular Matrix (ECM) volume > 27% by CMR at Visit 0.
Who cannot join
- Myocardial infarction, coronary artery bypass graft surgery or percutaneous coronary intervention within the previous 6 months.
- Probable alternative cause of patient's HF symptoms that in the opinion of the investigator primarily accounts for patient's dyspnoea such as significant pulmonary disease, anaemia or obesity. Specifically, patients with the below are excluded:
- Severe chronic obstructive pulmonary disease (COPD) (i.e., requiring home oxygen, chronic nebuliser therapy, or chronic oral steroid therapy), or Haemoglobin < 9 g/dl, or Body mass index (BMI) > 55 kg/m2. Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy.
- Clinically significant congenital heart disease. Presence of severe valvular heart disease. Atrial fibrillation or flutter with a resting ventricular rate > 100 bpm. Any medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
- Severe renal dysfunction at Visit 0, defined as estimated Glomerular Filtration Rate (eGFR) <30 mL/min (using Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI) calculation), or end-stage renal disease requiring dialysis.
- History of severe hepatic impairment or liver dysfunction at Visit 0, defined as total bilirubin above the upper limit of normal (ULN) (excluding patients with Gilbert's syndrome), aspartate aminotransferase (AST) or alanine transaminase (ALT) >3 times the ULN or alkaline phosphatase >2.5 times the ULN.
Show all 12Show fewer
- Prolonged corrected QT interval, defined as a corrected QT interval >500 msec on ECG using Bazett formula.
- Known hypersensitivity to any of the components of the investigational medicinal product (IMP).
- Use of other investigational drugs at the time of enrolment, or within 30 days or 5 half-lives of enrolment, whichever is longer.
- Fluvoxamine use within 28 days of Visit 0.
- Contraindication to MRI scanning or gadolinium-based contrast agent
- Pregnancy, lactation or planning pregnancy. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment, must agree to pregnancy tests at study visits as defined in the Section 7.2.5 and must agree to maintain highly effective contraception during the study and for 3 months thereafter. Similarly male participants with female partners of childbearing potential must agree to maintain highly effective contraception during the study and for 3 months thereafter.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Manchester University NHS Foundation Trust
Manchester
About this study
Official title: Circulating Biomarkers of Fibrosis and Cardiovascular Disease in Patients With Heart Failure With Preserved Ejection Fraction - Analysis of Samples Collected as Part of the PIROUETTE Trial
Heart failure with preserved ejection fraction (HFpEF) represents one of the largest unmet needs in cardiovascular medicine. Heart muscle scarring (myocardial fibrosis) is a key HFpEF disease mechanism and represents an important therapeutic target.
Myocardial fibrosis can be measured non-invasively using the cardiovascular magnetic resonance imaging (MRI) extracellular volume (ECV) technique. However, some patients cannot undergo MRI scanning, and it is expensive. Circulating biomarkers in the blood that are sensitive to changes in myocardial fibrosis would represent an attractive cheaper and accessible alternative.
This study aims to assess baseline levels of, and longitudinal change in, circulating biomarkers relating to fibrosis and cardiovascular disease in gifted samples from PIROUETTE trial participants, and evaluate the relationship between the biomarkers, anti-fibrotic treatment response and other study measurements.
Read the detailed description
Myocardial fibrosis, is a key HFpEF disease mechanism and represents an important therapeutic target.
Myocardial fibrosis is caused by excess secretion of collagen and other large molecules within the heart. Several of these molecules can be detected and measure in blood serum, thereby acting as non-invasive markers of myocardial fibrosis. Examples include, but are not limited to, precursors of type I and type 3 collagen.
In addition, gut microorganisms produce imidazole propionate (ImP), which can be detected in blood samples. This molecule has previously been associated with cardiovascular disease and heart failure and the investigators hypothesise that it may also be associated with myocardial fibrosis.
These circulating biomarkers of fibrosis are a cheaper and more accessible alternative for measurement of cardiac fibrosis compared to cardiovascular MRI ECV technique.
This study will investigate the association between circulating biomarkers of fibrosis, gut microbiome function and cardiovascular disease in samples from PIROUETTE.
- Being tested
- Pirfenidone
- Keywords
- Heart Failure, Heart Failure with Preserved Ejection Fraction, Myocardial Fibrosis, Myocardial Extracellular Volume, Pirfenidone
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PirfenidoneDrug
Intervention drug
| Study group | Role | What they receive |
|---|---|---|
| Pirfenidone | Pirfenidone 801mg capsule by mouth, three times a day (target dose) for 12 months Receives: Drug: Pirfenidone | |
| Placebo | Placebo capsule by mouth, three times a day (target dose) for 12 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
Circulating biomarkers of myocardial fibrosis
Examples include procollagen type I C-terminal propeptide (PICP) and collagen type I C-terminal telopeptide (CITP) in micrograms per litre
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2023
- Study start2 Mar 2017
- Primary completion29 Nov 2019
- Study completion29 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05826821
- Sponsor's protocol ID
- B01793
- Other IDs
- 320856
- Status last verified
- Apr 2023
- First submitted
- 6 Apr 2023
- Last updated
- 24 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating Biomarkers of Fibrosis and Cardiovascular Disease in Patients With Heart Failure With Preserved Ejection Fraction - Analysis of Samples Collected as Part of the PIROUETTE Trial
- ClinicalTrials.gov ID
- NCT05826821
- Acronym / sponsor ID
- B01793
- Keywords
- Heart Failure, Heart Failure with Preserved Ejection Fraction, Myocardial Fibrosis, Myocardial Extracellular Volume, Pirfenidone
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Study start
- 2 Mar 2017 (actual)
- Primary completion
- 29 Nov 2019 (actual)
- Study completion
- 29 Apr 2020 (actual)
- First posted
- 24 Apr 2023 (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.
Heart failure with preserved ejection fraction (HFpEF) represents one of the largest unmet needs in cardiovascular medicine. Heart muscle scarring (myocardial fibrosis) is a key HFpEF disease mechanism and represents an important therapeutic target.
Myocardial fibrosis can be measured non-invasively using the cardiovascular magnetic resonance imaging (MRI) extracellular volume (ECV) technique. However, some patients cannot undergo MRI scanning, and it is expensive. Circulating biomarkers in the blood that are sensitive to changes in myocardial fibrosis would represent an attractive cheaper and accessible alternative.
This study aims to assess baseline levels of, and longitudinal change in, circulating biomarkers relating to fibrosis and cardiovascular disease in gifted samples from PIROUETTE trial participants, and evaluate the relationship between the biomarkers, anti-fibrotic treatment response and other study measurements.
Detailed description
Myocardial fibrosis, is a key HFpEF disease mechanism and represents an important therapeutic target.
Myocardial fibrosis is caused by excess secretion of collagen and other large molecules within the heart. Several of these molecules can be detected and measure in blood serum, thereby acting as non-invasive markers of myocardial fibrosis. Examples include, but are not limited to, precursors of type I and type 3 collagen.
In addition, gut microorganisms produce imidazole propionate (ImP), which can be detected in blood samples. This molecule has previously been associated with cardiovascular disease and heart failure and the investigators hypothesise that it may also be associated with myocardial fibrosis.
These circulating biomarkers of fibrosis are a cheaper and more accessible alternative for measurement of cardiac fibrosis compared to cardiovascular MRI ECV technique.
This study will investigate the association between circulating biomarkers of fibrosis, gut microbiome function and cardiovascular disease in samples from PIROUETTE.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pirfenidone | – | Drug: PirfenidonePirfenidone 801mg capsule by mouth, three times a day (target dose) for 12 months |
| Placebo | – | –Placebo capsule by mouth, three times a day (target dose) for 12 months |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with heart failure with preserved ejection fraction and myocardial fibrosis
Key inclusion criteria (7 listed)
- Written informed consent.
- Male or female; aged 40 years or older.
- HF, defined as one symptom present at the time of screening, and one sign present at the time of screening or in the previous 12 months. Symptoms and signs are defined as:
- Symptoms: dyspnoea on exertion, orthopnoea or paroxysmal nocturnal dyspnoea Signs: peripheral oedema, crackles on chest auscultation post-cough, raised jugular venous pressure or chest x-ray demonstrating pleural effusion, pulmonary congestion, or cardiomegaly
- Left Ventricular Ejection Fraction (LVEF) > 45% at Visit 0, (any local LVEF measurement made using echocardiography or CMR).
Key exclusion criteria (12 listed)
- Myocardial infarction, coronary artery bypass graft surgery or percutaneous coronary intervention within the previous 6 months.
- Probable alternative cause of patient's HF symptoms that in the opinion of the investigator primarily accounts for patient's dyspnoea such as significant pulmonary disease, anaemia or obesity. Specifically, patients with the below are excluded:
- Severe chronic obstructive pulmonary disease (COPD) (i.e., requiring home oxygen, chronic nebuliser therapy, or chronic oral steroid therapy), or Haemoglobin < 9 g/dl, or Body mass index (BMI) > 55 kg/m2. Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy.
- Clinically significant congenital heart disease. Presence of severe valvular heart disease. Atrial fibrillation or flutter with a resting ventricular rate > 100 bpm. Any medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
- Severe renal dysfunction at Visit 0, defined as estimated Glomerular Filtration Rate (eGFR) <30 mL/min (using Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI) calculation), or end-stage renal disease requiring dialysis.
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 |
|---|---|---|
| PirfenidoneIntervention drug | Drug | Pirfenidone |
Primary outcome
Circulating biomarkers of myocardial fibrosis
Time frame: 12 months
Examples include procollagen type I C-terminal propeptide (PICP) and collagen type I C-terminal telopeptide (CITP) in micrograms per litre
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 24 Apr 2023.
- Individual participant dataSharing planned: Undecided
Related trials for Heart Failure With Preserved Ejection Fraction
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
RecruitingObservational study
Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
Inflammation Biomarkers, Heart Failure
Recruiting
Remote Rehabilitation in Patients With HFpEF (PATRON-HF)
Heart Failure With Preserved Ejection Fraction
Recruiting
ELEVATE-HFpEF Clinical Study
Heart Failure With Preserved Ejection Fraction (HFpEF)
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure With Preserved Ejection Fraction, run by Manchester University NHS Foundation Trust 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 7 inclusion and 12 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 24 Apr 2023. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Circulating biomarkers of myocardial fibrosis (time frame: 12 months). 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 24 Apr 2023.