Clinical trial NCT04957147: Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy
Official title: The REMIT-DCM Study: Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Dilated Cardiomyopathy
Keywords: Dilated cardiomyopathy
Left ventricular reverse remodelling
Heart failure
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Royal Brompton & Harefield NHS Foundation Trust
First posted: 2021-07-12
Enrollment: 103
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Group A: There are 3 routes via which patients with DCM may be recruited:

1. Patients from the Royal Brompton \& Harefield NHS Trust clinical service (inpatients, patients from clinics and patients referred for a CMR).
2. Patients with DCM may also be recruited from collaborating district general hospitals, defined as Patient Identification Centres (PICs). Clinicians at these sites have agreed to identify suitable patients encountered within their routine practice.
3. Patients will be able to self-refer via The Heart Hive for consideration by the study team. The Heart Hive (https://www.thehearthive.org/) is an online platform that offers patients with cardiomyopathy and healthy volunteers the opportunity to connect with researchers regarding participation in research studies.

Brief summary: Approximately 30-40% of patients with non-ischaemic dilated cardiomyopathy (DCM) undergo significant left ventricular reverse remodelling in response to guideline-directed therapies. This is characterised by improvement in systolic dysfunction and regression of left ventricular dilatation. In some patients, extensive left ventricular reverse remodelling is accompanied by resolution of symptoms and normalisation of cardiac biomarkers, resulting in a state of clinical remission.

The mechanistic drivers behind left ventricular reverse remodelling and clinical remission are poorly understood. Current techniques to predict ventricular remodelling trajectory and clinical remission in patients with recent-onset DCM are limited.

The purpose of this study is to characterise predictors and markers of left ventricular reverse remodelling and clinical remission in patients with recent-onset DCM using molecular markers, genetics and advanced CMR imaging.

Detailed description: The REMIT-DCM study is a single-centre pilot observational cohort study. 70 patients with recent-onset DCM (Group A) and up to 40 healthy volunteers (Group B) will be recruited. Patients with DCM will be recruited over a 2-year period and will be followed up for 12 months. Subjects in Group A may be offered an optional further study visit at 24-48 months after enrolment in order to assess whether cardiac remodelling and clinical remission are sustained over the intermediate-term.

Patients with DCM (Group A) will attend 3 study visits at The Royal Brompton Hospital (baseline, 2-3 months and 12 months). Each study visit will involve a clinical consultation, blood sample collection (including routine clinical blood tests and sample storage for exploratory biomarkers), urine sample collection, 12-lead ECG, health questionnaire completion and a cardiovascular magnetic resonance scan (CMR). If patients are unable to have a CMR, 3D transthoracic echocardiography will be performed.

Healthy volunteers will attend a single study visit at The Royal Brompton Hospital. This will involve a clinical consultation, blood sample collection (including routine clinical blood tests and sample storage for exploratory biomarkers), urine sample collection, 12-lead ECG, health questionnaire completion and a CMR.

Eligibility criteria: For DCM cohort (Group A):

Inclusion Criteria:

* Age ≥16.
* Able to give informed consent.
* Confirmed DCM with symptom-onset within the last 6 months and LVEF ≤ 45%. The diagnosis of DCM will be confirmed using the European Society of Cardiology definition, based on reduced LVEF and elevated LV end-diastolic volume indexed to body surface area, compared to published age- and sex-specific reference values

Exclusion Criteria:

* Significant coronary artery heart disease, defined as a stenosis of \>50% of an epicardial coronary artery affecting the proximal or mid-portion of the vessel on invasive angiography or computed tomography coronary angiography (CTCA), previous percutaneous coronary intervention, CMR late gadolinium enhancement pattern suggestive of previous myocardial infarction of ≥ 2 segments of ≥ 50% transmural infarction of the LV wall.
* High suspicion of concomitant hypertrophic cardiomyopathy, amyloidosis, Fabry disease, sarcoidosis, active myocarditis, Chagas disease or hemochromatosis.
* History of primary valvular heart disease or congenital heart disease.
* Severe, untreated or untreatable hypertension (systolic blood pressures routinely \>180 mm Hg and/or diastolic blood pressures \>120 mm Hg)
* Pregnancy and/or breastfeeding.
* Severe renal disease (GFR \<15 mls/min).

For healthy volunteer cohort (Group B):

Inclusion Criteria:

* Age ≥16.
* Able to give informed consent.

Exclusion criteria:

* Participants with any clinically significant cardiovascular or metabolic disease.
* Participants taking prescription medicines for significant cardiovascular or metabolic disease.
* Female subjects if they are pregnant or breastfeeding at the time of recruitment.

Primary outcomes:
measure: Clinical remission
timeFrame: 12-months
Secondary outcomes:
measure: Left ventricular reverse remodelling
timeFrame: 12-months
measure: Left ventricular reverse remodelling
timeFrame: 12-months
measure: Major adverse cardiovascular events
timeFrame: 12-months
measure: Change in health status using Kansas City Cardiomyopathy questionnaire
timeFrame: 12-months
measure: Change in health status using SF-12 questionnaire
timeFrame: 12-months
measure: Change in health status using EQ-5D questionnaire
timeFrame: 12-months
measure: Sustained clinical remission at 24-48 months after enrolment
timeFrame: 48 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College
Study officials:
affiliation: Imperial College London
name: Sanjay K Prasad
role: PRINCIPAL_INVESTIGATOR
References: