Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy

Dilated Cardiomyopathy Clinical Trial

— REMIT-DCM  

Official title:

The REMIT-DCM Study: Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04957147
• Other study ID #: 19IC5198
• Status: Completed
• Start date: August 1, 2019
• Est. completion date: May 1, 2023

Study information

• Verified date: December 2023
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: May 1, 2023
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy

Intervention

Other:
• 12 months of guideline-directed heart failure therapy
Standard guideline-directed heart failure drug +/- device therapy

Locations

Country	Name	City	State
United Kingdom	Imperial College	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Royal Brompton & Harefield NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical remission	If all 3 of the following criteria are met at 12-month assessment: i. Increase in left ventricular ejection fraction (LVEF) by = 10% to a value = 50% and decrease in indexed left ventricular end diastolic volume (LVEDV) to within normal range according to age-/sex-corrected normograms.; ii. NYHA class I.; iii. NT-Pro BNP <250 ng/L.	12-months
Secondary	Left ventricular reverse remodelling	Evaluated by changes in indexed left ventricular end systolic volume (LVESV), indexed LVEDV and LVEF between baseline and 12 months.	12-months
Secondary	Left ventricular reverse remodelling	Evaluated using a pre-specified threshold: patients with DCM will be divided into 2 groups at the 12-month timepoint: i. Left ventricular reverse remodelling: an increase in LVEF by = 10% to a value = 40%; and a decrease in indexed LVEDV by = 10%.; ii. No left ventricular reverse remodelling: no increase in LVEF by = 10% to a value = 40% and/or no decrease in indexed LVEDV by = 10%.	12-months
Secondary	Major adverse cardiovascular events	Composite of cardiovascular death, major heart failure or major arrhythmic events.	12-months
Secondary	Change in health status using Kansas City Cardiomyopathy questionnaire	Change in Kansas City Cardiomyopathy questionnaire scores from baseline to 12-months	12-months
Secondary	Change in health status using SF-12 questionnaire	Change in SF-12 questionnaire scores from baseline to 12-months	12-months
Secondary	Change in health status using EQ-5D questionnaire	Change in EQ-5D questionnaire scores from baseline to 12-months	12-months
Secondary	Sustained clinical remission at 24-48 months after enrolment	For those in clinical remission at 12-month timepoint, the proportion that have sustained clinical remission at 24-48 months after enrolment.	48 months