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Routine vs Selective Cardiac Magnetic Resonance in Non-Ischemic Heart Failure (OUTSMART)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Ottawa Heart Institute Research Corporation
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
The Finnish Funding Agency for Technology and Innovation (TEKES)
Information provided by (Responsible Party):
Rob Beanlands, University of Ottawa Heart Institute
ClinicalTrials.gov Identifier:
NCT01281384
First received: January 20, 2011
Last updated: August 29, 2014
Last verified: August 2014

January 20, 2011
August 29, 2014
January 2011
September 2015   (final data collection date for primary outcome measure)
Frequency of definitive diagnoses [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Following the completion of all baseline testing (including echo) in the selective arm and baseline testing + CMR in the routine arm, the treating physician will assign a diagnosis on a standardized template using all available information. The diagnosis of non-ischemic cardiomyopathies will be based upon recent Canadian Consensus Statement.

Expected Result - The routine CMR group will have a significantly higher rate of specific diagnoses for (a) heart failure with preserved systolic function (HFPSF) and (b) dilated cardiomyopathy (DCM) diagnoses (i.e. fewer idiopathic DCM) than the selective CMR group.

Frequency of definitive diagnoses [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Following the completion of all baseline testing (including echo) in the selective arm and baseline testing + CMR in the routine arm, the treating physician will assign a diagnosis on a standardized template using all available information. The diagnosis of non-ischemic cardiomyopathies will be based upon recent Canadian Consensus Statement.

Expected Result - The routine CMR group will have a significantly higher rate of specific diagnoses for(a) HFPSF and (b) dilated cardiomyopathy (DCM) diagnoses (i.e. fewer idiopathic DCM) than the selective CMR group.

Complete list of historical versions of study NCT01281384 on ClinicalTrials.gov Archive Site
  • Treatment effects [ Time Frame: 3 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    Telephone follow up will be conducted. The presence of each HF medication class will be re-assessed in addition to the overall number of cardiac medications. The presence of advanced HF therapies will additionally be recorded at each follow-up visit including: implantable device, electrophysiologic study/ablation, cardiac surgery/transplantation, and disease specific therapies (eg. phlebotomy for hemochromatosis; steroids for sarcoidosis). The HF specialist supervising the follow-up visits will also be asked to reassess the HF etiology during each encounter.
  • Clinical Endpoints [ Time Frame: 3 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    CCE (Death, Cardiovascular (CV) death, HF admission), left ventricular (LV) Function, QoL, Referral to HF clinic, Costs and Safety) will be assessed.
  • Resource utilization and costs [ Time Frame: 3 months, 1,2 and 3 years ] [ Designated as safety issue: No ]
    Regression methods will be used to assess the incremental costs associated with the routine use of CMR.
  • HF Diagnosis Variability: [ Time Frame: 3 months, 1,2 and 3 years ] [ Designated as safety issue: No ]
    A local independent blinded heart failure expert will also be asked to diagnose the HF etiology in a subset of 100 patients (~10%) in order to determine inter-observer variability in each of the CMR selective and standard arms.
  • Echo/CMR variability: [ Time Frame: baseline ] [ Designated as safety issue: No ]
    An anonymized copy of each CMR and each available echo will be sent to a core lab. A second interpretation will occur at the core lab in 10% of cases in order to assess reproducibility and quality assurance of the results.
  • Treatment effects [ Time Frame: 3 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    Telephone follow up will be conducted. The presence of each HF medication class will be re-assessed in addition to the overall number of cardiac medications. The presence of advanced HF therapies will additionally be recorded at each follow-up visit including: implantable device, electrophysiologic study/ablation, cardiac surgery/transplantation, and disease specific therapies (eg. phlebotomy for hemochromatosis; steroids for sarcoidosis). The HF specialist supervising the follow-up visits will also be asked to reassess the HF etiology during each encounter.
  • Clinical Endpoints [ Time Frame: 3 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    CCE (Death, CV death, HF admission), LV Function, QoL, Referral to HF clinic, Costs and Safety) will be assessed.
  • Resource utilization and costs [ Time Frame: 3 months, 1,2 and 3 years ] [ Designated as safety issue: No ]
    Regression methods will be used to assess the incremental costs associated with the routine use of CMR.
  • HF Diagnosis Variability: [ Time Frame: 3 months, 1,2 and 3 years ] [ Designated as safety issue: No ]
    A local independent blinded heart failure expert will also be asked to diagnose the HF etiology in a subset of 100 patients (~10%) in order to determine inter-observer variability in each of the CMR selective and standard arms.
  • Echo/CMR variability: [ Time Frame: baseline ] [ Designated as safety issue: No ]
    An anonymized copy of each CMR and each available echo will be sent to a core lab. A second interpretation will occur at the core lab in 10% of cases in order to assess reproducibility and quality assurance of the results.
Not Provided
Not Provided
 
Routine vs Selective Cardiac Magnetic Resonance in Non-Ischemic Heart Failure
Routine vs Selective Cardiac Magnetic Resonance in Non-Ischemic Heart Failure (OUTSMART-HF) Project I-B of Imaging Modalities to Assist With Guiding Therapy and the Evaluation of Patients With Heart Failure (IMAGE-HF)

Uncovering the underlying cause of heart failure can be quite challenging and doctors often rely on imaging tests such as echo (heart ultrasound) to provide the answers. Cardiac MRI is emerging as another promising test because it gives very precise information on heart function and the amount of scarring in the muscle. Heart failure patients are increasingly being sent for cardiac MRI but the potential advantage that this test offers over others such as echo has not been fully explored.

The purpose of this study is to determine if cardiac MRI provides more information on the cause of heart failure than traditional tests such as echo. In addition, if the information provided by this test always leads to an overall improvement in a patient's heart condition over time.

This is a randomized study where subjects referred for clinically indicated heart failure workup to determine the best clinical management will undergo standard heart failure testing (including echo) OR standard testing PLUS cardiac MRI.

Primary objective: Compare the diagnostic yield of routine cardiac magnetic resonance versus standard care (i.e. echocardiography with only selective use of CMR) in patients with non-ischemic heart failure. The diagnostic categories of HF to be considered in this study include: idiopathic dilated cardiomyopathy, infiltrative cardiomyopathy, inflammatory cardiomyopathy, hypertrophic cardiomyopathy, heart failure with preserved ejection fraction (HFPEF), ischemic cardiomyopathy, mixed etiology and other (e.g. pericardial, congenital, non-compaction, right ventricular failure).

Secondary objectives: Determine the effects that routine use of CMR in non-ischemic HF has on therapeutic decisions, on the Composite Clinical Endpoint (CCE), cardiac function, symptoms, quality of life (QoL), and costs. Ancillary measurements will include the safety of imaging tests and adverse reactions to gadolinium contrast agent.

Hypotheses:

Primary hypothesis: Routine use of CMR (vs. selective use) will lead to a more specific diagnostic characterization of the underlying etiology of non-ischemic heart failure. This will lead to a reduction in the non-specific diagnoses of idiopathic dilated cardiomyopathy and HFPEF.

Secondary hypotheses: Routine use of CMR will have a significant impact on treatment decisions, (1) lead to more disease specific therapies and/or (2) cause a significant change in the number and class of HF meds, during follow-up. The routine CMR group will also have improved clinical outcomes (CCE), symptoms and QoL and decreased costs to the standard of care group during follow-up.

Design

Randomized controlled trial comparing i) routine CMR vs. ii) echocardiography with selective CMR in patient with HF due to a non-ischemic cardiomyopathy (NICM) and/or heart failure with preserved ejection fraction (HFPEF).

Among patients enrolled in Level I of IMAGE-HF, it is expected that 504 will have known NICM (or strongly suspected based on young age, absent risk factors and presenting history) and/or HFPEF. (Figure 1).

Tertiary care sites (in Canada and Finland) with dedicated HF programs will participate in the study. Consecutive patients will be enrolled at sites with dedicated CMR programs (defined as minimum 200 cases/year and maximum 2 weeks waiting time in the majority of patients) and randomized to routine CMR or selective CMR. Non-ischemic HF patients from sites without dedicated CMR programs will be included in a registry of patients undergoing routine HF care (i.e. selective use of CMR). Participants in the selective CMR arm may ONLY undergo CMR for a suspicion of: 1) infiltrative myocardial disease, 2) arrhythmogenic right ventricular cardiomyopathy, 3) adult congenital heart disease or 4) pericardial disease following standard HF care including echocardiography. Other tertiary sites may be added in year 2-3 depending on recruitment needs and registry sites may become randomization sites if the experience and wait-time criteria are met.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Heart Failure
  • Other: Advanced Imaging
    Other Name: Cardiac Magnetic Resonance Imaging (CMR)
  • Other: Standard Imaging
    Other Name: Echocardiography
  • Active Comparator: Standard imaging (echocardiography)
    Subjects will undergo their clinically indicated echocardiogram as ordered by their attending physician.
    Intervention: Other: Standard Imaging
  • Active Comparator: Advanced Imaging (Cardiac MRI)
    Subjects will undergo their clinically indicated echo as ordered by their attending physician, plus a cardiac MRI, which will be scheduled within 14 days of the echo.
    Intervention: Other: Advanced Imaging
Paterson I, Wells GA, Ezekowitz JA, White JA, Friedrich MG, Mielniczuk LM, O'Meara E, Chow B, DeKemp RA, Klein R, Dennie C, Dick A, Coyle D, Dwivedi G, Rajda M, Wright GA, Laine M, Hanninen H, Larose E, Connelly KA, Leong-Poi H, Howarth AG, Davies RA, Duchesne L, Yla-Herttuala S, Saraste A, Farand P, Garrard L, Tardif JC, Arnold M, Knuuti J, Beanlands R, Chan KL. Routine versus selective cardiac magnetic resonance in non-ischemic heart failure - OUTSMART-HF: study protocol for a randomized controlled trial (IMAGE-HF (heart failure) project 1-B). Trials. 2013 Oct 12;14:332. doi: 10.1186/1745-6215-14-332.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
504
June 2016
September 2015   (final data collection date for primary outcome measure)

Inclusion Criteria: Patients with new or worsening HF as above AND

  1. age > 18
  2. working clinical diagnosis (known or highly suspected) of non-ischemic cardiomyopathy (NICM) (ie. no significant obstructive CAD; no prior myocardial infarction (MI); negative non-invasive tests; and/or clinical scenario strongly suspicious for NICM) OR clinical diagnosis of HFPSF (Signs or symptoms of heart failure with a left ventricular ejection fraction (LVEF) ≥ 40%)
  3. Class II-IV New York Heart Association (NYHA) HF symptoms

Exclusion Criteria:

  1. Prior CMR and no major change in clinical condition
  2. well-documented specific etiology (eg known amyloidosis or hemochromatosis)
  3. documented obstructive CAD (at least one stenosis >50% in major epicardial vessels)
  4. documented previous MI
  5. severe medical conditions that significantly affect the patient's outcome (eg. active malignancy)
  6. ongoing need for advanced cardiac life support (eg IABP)
  7. severe valvular heart disease requiring surgery within the next 6 months
  8. contraindications to CMR (e.g. certain metallic implants, severe claustrophobia)
  9. contraindications to gadolinium contrast agent (GFR < 30ml/min/1,72m2, pregnancy)
  10. inability to give informed consent
Both
18 Years and older
No
Contact: Linda M Garrard, RN, BScN 613-761-4192 lgarrard@ottawaheart.ca
Contact: Cathy Kelly, RN 613-761-4809 ckelly@ottawaheart.ca
Canada,   Finland
 
NCT01281384
Project I-B, CIF-99470
Yes
Rob Beanlands, University of Ottawa Heart Institute
Ottawa Heart Institute Research Corporation
  • Canadian Institutes of Health Research (CIHR)
  • The Finnish Funding Agency for Technology and Innovation (TEKES)
Study Director: Rob SB Beanlands, MD, FRCP C Universityof Ottawa Heart Institute
Principal Investigator: Ian Paterson, MD University of Alberta
Ottawa Heart Institute Research Corporation
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP