Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03094143
Previous Study | Return to List | Next Study

Early Valve Replacement Guided by Biomarkers of LV Decompensation in Asymptomatic Patients With Severe AS (EVoLVeD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03094143
Recruitment Status : Recruiting
First Posted : March 29, 2017
Last Update Posted : October 11, 2018
Sponsor:
Collaborator:
Sir Jules Thorn Charitable Trust
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:

Aortic stenosis is the most common valvular disease in the Western world. It is caused by progressive narrowing of the aortic valve leading to increased strain on the heart muscle which has to work increasingly hard to pump blood through the narrowed valve. Over time the heart muscle thickens to generate more force, but eventually the heart fails leading to death if the valve is not replaced with an operation. No medical treatments exist to stop or reverse the heart valve narrowing. Current clinical guidelines suggest that an operation should be performed only when symptoms develop or the heart muscle is visibly weak on cardiac ultrasound scanning. However, symptoms can be difficult to interpret and in many patients the heart muscle has become irreversibly damaged and the heart fails to recover following surgery.

Using MRI scans of the heart, the investigators have identified heart scarring which seems to develop as the heart muscle thickens. Several studies now show that people who have developed this scarring are more likely to suffer poor outcomes including death. The investigators have also identified clinical risks that predict the presence of scarring.

The investigators propose a study where patients with severe aortic stenosis but no indications for valve replacement as per current guidelines are assessed for those clinical risks. If a participant's risk of having scarring is higher they will undergo a cardiac MRI scan. If scarring is present participants will be randomised to routine clinical care, or referral for valve replacement surgery. Participants with no evidence of scarring will be randomised routine care with study follow or not. The investigators of this study hypothesize that early surgery will lead to fewer complications and reduced risk of death compared to standard care.


Condition or disease Intervention/treatment Phase
Aortic Valve Stenosis Hypertrophy, Left Ventricular Procedure: Aortic valve intervention Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants are randomised based on the result of the cardiac MRI. Participants who have mid wall fibrosis (heart scarring) are randomised to receive either early surgical intervention (group A) or routine care (group B). Participants who have no mid wall fibrosis are randomised to routine care with study follow up (group C) or without study follow up (group D).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The result of the cardiac MRI will be blinded to care provider, participant and investigator. Group A will be unblinded, as participants can only enter group A if mid-wall fibrosis is present. Groups B and C will appear identical and the groups combined so the presence of mid-wall fibrosis will be blinded. Group D will be unblinded, as participants can only enter group D if mid-wall fibrosis is not present.

Outcome assessors will be blinded to allocation in all groups where outcome is adjudicated (groups A, B and C)

Primary Purpose: Treatment
Official Title: Early Valve Replacement Guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients With Severe Aortic Stenosis
Actual Study Start Date : July 21, 2017
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A: Early intervention
Patients will be referred immediately for aortic valve intervention.
Procedure: Aortic valve intervention
The choice of either surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI) will be made by the local clinical team according to local policies. In patients undergoing surgical replacement the choice of surgical technique and type of valve replacement used will be at the discretion of the operating surgeon. Patients found to have significant coronary artery disease requiring concomitant coronary artery bypass surgery will not be excluded. Similarly the choice of TAVI valve and need for percutaneous coronary intervention will be made by the TAVI heart team. The procedure should be performed as soon as possible and ideally within four months of randomisation and allocation to group A.

No Intervention: Group B: Routine care
Patients will be invited back for clinical follow up according to local policy. Decision making regarding future aortic valve intervention will be taken by the participant's clinical team (cardiologist and cardiac surgeon).
No Intervention: Group C: Routine care
Patients will be invited back for clinical follow up according to local policy. Decision making regarding future aortic valve intervention will be taken by the patient's clinical team (cardiologist and cardiac surgeon). Group C will appear identical to Group B
No Intervention: Group D: No further study follow up
Patients will be invited back for clinical follow up according to local policy. Decision making regarding future aortic valve intervention will be taken by the patient's clinical team (cardiologist and cardiac surgeon). No further study follow up will take place but personal data will be retained for future data linkage.



Primary Outcome Measures :
  1. Composite of all-cause mortality or unplanned aortic stenosis-related hospitalisation [ Time Frame: Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years) ]

    The first event of all-cause mortality or unplanned aortic stenosis-related hospitalisation

    Unplanned aortic stenosis-related hospitalisation is defined as an unplanned admission with syncope, heart failure, chest pain or arrhythmia (ventricular arrhythmia or second or third degree heart block) attributed to aortic stenosis. This endpoint will be adjudicated by two independent investigators blinded to the details of randomisation following review of the case notes and hospital records.



Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: Randomisation through to study completion, an average of 2.75 years ]
  2. Cardiovascular death [ Time Frame: Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years) ]
  3. AS-related death [ Time Frame: Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years) ]
    AS-related death is a death where aortic stenosis has been listed as a contributory cause by the clinical care team on the patient's official death certificate.

  4. Sudden cardiac death [ Time Frame: Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years) ]
  5. Unplanned aortic-stenosis related hospitalisation [ Time Frame: Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years) ]
    Unplanned aortic stenosis-related hospitalisation is defined as an unplanned admission with syncope, heart failure, chest pain or arrhythmia (ventricular arrhythmia or second or third degree heart block) attributed to aortic stenosis.

  6. WHODAS 2.0 (12 item) [ Time Frame: At study completion (mean follow up is expected to be an average of 2.75 years) ]
    The World Health Organization Disability Assessment Schedule (WHODAS 2.0) is a generic assessment instrument developed by WHO to provide a standardized method for measuring health and disability across cultures.

  7. LV systolic function [ Time Frame: Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years) ]
    The development of LV systolic dysfunction (EF <50% quantitatively or at least mild LV dysfunction qualitatively)

  8. NYHA status [ Time Frame: At study completion (mean follow up is expected to be an average of 2.75 years) ]
    Self reported patient symptoms on a scale of I-IV (I = No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, IV = Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.)

  9. Permanent pacemaker insertion, cardiac resynchronisation therapy or automated implantable cardioverter defibrillator [ Time Frame: Randomisation to through to study completion (mean follow up is expected to be an average of 2.75 years) ]
    To compare between study arms the number of participants who have had a permanent pacemaker insertion, cardiac resynchronisation therapy or automated implantable cardioverter defibrillator

  10. Stroke [ Time Frame: Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years) ]
  11. Endocarditis [ Time Frame: Randomisation to through to study completion (mean follow up is expected to be an average of 2.75 years) ]
    To compare between study arms the number of participants who have endocarditis

  12. Post-operative complications following aortic valve intervention [ Time Frame: 30 days post aortic valve intervention ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Severe aortic stenosis (aortic valve jet velocity ≥4.0 m/s, or aortic valve area indexed to body surface area <0.6cm2/m2 with aortic jet velocity ≥3.5m/s)
  2. Age over 18 years
  3. No symptoms attributable to aortic stenosis that require aortic valve replacement

Exclusion Criteria:

  1. Deemed lower risk for mid-wall fibrosis on screening
  2. Planned cardiac surgery
  3. Previous valve replacement
  4. Severe hypertension (systolic >180 or diastolic >110 mmHg)
  5. Acute pulmonary oedema or cardiogenic shock
  6. Left ventricular ejection fraction <50% on cardiac MRI
  7. Significant abnormalities on cardiac MRI that would prevent enrolment
  8. Coexistent severe aortic regurgitation or mitral regurgitation
  9. Coexistent mitral stenosis greater than mild in severity
  10. Coexistent hypertrophic cardiomyopathy or cardiac amyloidosis
  11. Any contraindication to MRI scanning (such as permanent pacemaker)
  12. Advanced renal impairment (glomerular filtration rate <30 mL/min/1.73 m2)
  13. Pregnancy or breast feeding
  14. Patient judged to be unfit to be considered for aortic valve replacement or transcatheter aortic valve implantation
  15. Patient declines to consider undergoing valve replacement surgery or transcatheter aortic valve implantation
  16. Inability to give informed consent
  17. Previous randomisation into this study

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): NCT03094143


Contacts
Layout table for location contacts
Contact: EVoLVeD Trial Manager evolved.trial@ed.ac.uk

Locations
Layout table for location information
United Kingdom
NHS Lothian Recruiting
Edinburgh, United Kingdom
Sponsors and Collaborators
University of Edinburgh
Sir Jules Thorn Charitable Trust
Investigators
Layout table for investigator information
Principal Investigator: Marc Dweck University of Edinburgh

Layout table for additonal information
Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT03094143     History of Changes
Other Study ID Numbers: 15/JTA
First Posted: March 29, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: It is planned that an anonymised raw dataset will be shared under a controlled access model. It will be available following primary publication. Requests will be made in accordance with Edinburgh Clinical Trials Unit policy at the time of release.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Constriction, Pathologic
Hypertrophy
Aortic Valve Stenosis
Hypertrophy, Left Ventricular
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Cardiomegaly