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Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy (REMIT-DCM)

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ClinicalTrials.gov Identifier: NCT04957147
Recruitment Status : Recruiting
First Posted : July 12, 2021
Last Update Posted : July 12, 2021
Sponsor:
Collaborator:
Royal Brompton & Harefield NHS Foundation Trust
Information provided by (Responsible Party):
Imperial College London

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.


Condition or disease Intervention/treatment
Dilated Cardiomyopathy Other: 12 months of guideline-directed heart failure therapy

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.

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Study Type : Observational
Estimated Enrollment : 110 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The REMIT-DCM Study: Reverse Remodelling and Remission Markers in the Serial Evaluation of Recent-onset Dilated Cardiomyopathy
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : September 28, 2022
Estimated Study Completion Date : September 28, 2022


Group/Cohort Intervention/treatment
Group A: patients with dilated cardiomyopathy
Patients with recent-onset dilated cardiomyopathy
Other: 12 months of guideline-directed heart failure therapy
Standard guideline-directed heart failure drug +/- device therapy

Group B: healthy volunteers
Healthy volunteers with no known heart disease



Primary Outcome Measures :
  1. Clinical remission [ Time Frame: 12-months ]

    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.



Secondary Outcome Measures :
  1. Left ventricular reverse remodelling [ Time Frame: 12-months ]
    Evaluated by changes in indexed left ventricular end systolic volume (LVESV), indexed LVEDV and LVEF between baseline and 12 months.

  2. Left ventricular reverse remodelling [ Time Frame: 12-months ]

    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%.


  3. Major adverse cardiovascular events [ Time Frame: 12-months ]
    Composite of cardiovascular death, major heart failure or major arrhythmic events.

  4. Change in health status using Kansas City Cardiomyopathy questionnaire [ Time Frame: 12-months ]
    Change in Kansas City Cardiomyopathy questionnaire scores from baseline to 12-months

  5. Change in health status using SF-12 questionnaire [ Time Frame: 12-months ]
    Change in SF-12 questionnaire scores from baseline to 12-months

  6. Change in health status using EQ-5D questionnaire [ Time Frame: 12-months ]
    Change in EQ-5D questionnaire scores from baseline to 12-months

  7. Sustained clinical remission at 24-48 months after enrolment [ Time Frame: 48 months ]
    For those in clinical remission at 12-month timepoint, the proportion that have sustained clinical remission at 24-48 months after enrolment.


Biospecimen Retention:   Samples With DNA
Blood and urine samples


Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04957147


Contacts
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Contact: Daniel J Hammersley, MBBS 020 7352 8121 ext 88814 d.hammersley@nhs.net

Locations
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United Kingdom
Imperial College Recruiting
London, United Kingdom, SW3 6LY
Contact: Daniel J Hammersley, MBBS    020 7352 8121 ext 88814    d.hammersley@nhs.net   
Sponsors and Collaborators
Imperial College London
Royal Brompton & Harefield NHS Foundation Trust
Investigators
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Principal Investigator: Sanjay K Prasad Imperial College London
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT04957147    
Other Study ID Numbers: 19IC5198
First Posted: July 12, 2021    Key Record Dates
Last Update Posted: July 12, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
Dilated cardiomyopathy
Left ventricular reverse remodelling
Heart failure
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Cardiomegaly