Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001254280
Ethics application status
Approved
Date submitted
20/07/2018
Date registered
25/07/2018
Date last updated
22/06/2025
Date data sharing statement initially provided
11/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
REsolution of LEft VENTtricular thrombus (RELEVENT)
Scientific title
A Prospective Randomized Open, Blinded End-point controlled study evaluating the resolution and recurrence of left ventricular thrombus with different anti coagulation strategies
Secondary ID [1] 295613 0
Nil
Universal Trial Number (UTN)
U1111-1216-0447
Trial acronym
RELEVENT study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
left ventricular thrombus 308938 0
Condition category
Condition code
Cardiovascular 307839 307839 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised 1:1 to either warfarin or a Direct Oral Anti-Coagulant (DOAC).

Participants randomised to a DOAC can be treated with either a factor Xa inhibitor (apixaban or rivaroxaban) or a direct thrombin inhibitor (dabigatran). The choice of DOAC is made according to local availability and clinical judgment and preference.

The dose of DOAC will be the same as recommended by the manufacturer for stroke prevention in atrial fibrillation, with appropriate adjustment for age, body weight, creatinine clearance and bleeding risk. Recommended doses for DOACs for stroke prevention in atrial fibrillation are:

DOAC
Apixaban: Standard Dose 5 mg twice daily, Reduced Dose 2.5 mg twice daily
Rivaroxaban: Standard Dose 20 mg once daily, Reduced Dose 15 mg once daily
Dabigatran: Standard Dose 150 mg twice daily, Reduced Dose 110 mg twice daily

Treatment will be continued for 3 months.
Intervention code [1] 301919 0
Treatment: Drugs
Comparator / control treatment
Warfarin oral tablets for 3 months. Participants may be heparinized with low molecular weight heparin or unfractionated heparin until therapeutic INR is >2.0. Subsequent dosing of warfarin is determined by the INR which will be maintained in the range of 2.0 - 3.0. Upon discharge from hospital, INRs and warfarin dosing will be managed by general practitioners (GP).
Control group
Active

Outcomes
Primary outcome [1] 306814 0
Resolution of LV thrombus, with no CV death, stroke, systemic embolism or major bleeding at 3 months post randomisation. The imaging modality used to detect LV thrombus can be any of echocardiogram with or without contrast agent, cardiac CT, or cardiac MRI scan. The primary outcome will be assessed blind to treatment group in the following ways: • Presence of LV thrombus on imaging will be assessed by a core lab blinded to randomised treatment allocation. • Occurrence of CV death, stroke, systemic embolism or major bleeding events will be adjudicated by blinded review of relevant medical information provided to a clinical outcome adjudication committee.
Timepoint [1] 306814 0
Primary endpoint assessed 3-months post randomisation
Secondary outcome [1] 349835 0
Individual components of the primary outcome: Resolution of LV thrombus, absence of CV death, stroke, systemic embolism or major bleeding (defined as BARC Type 3 bleeding or above) within 3-month treatment period, as determined by independent review of images and independent adjudication of reported clinical events.
Timepoint [1] 349835 0
3 months post randomisation
Secondary outcome [2] 349836 0
Days alive and out of hospital within 3 months as determined through self-report and review of medical records.
Timepoint [2] 349836 0
3 months post randomisation
Secondary outcome [3] 411422 0
Quality of Life as determined by the EQ-5D-5L questionnaire.
Timepoint [3] 411422 0
3 months post randomisation
Secondary outcome [4] 411423 0
Participant reported health and disability as determined through the WHODAS 2.0 12-scale questionnaire.
Timepoint [4] 411423 0
3 months post randomisation
Secondary outcome [5] 411424 0
Change in LV thrombus volume/diameter between imaging performed at baseline and at the 3-month follow-up timepoint as determined by blinded review of images by a core laboratory. The imaging modality used to detect LV thrombus can be any of echocardiogram with or without contrast agent, cardiac CT, or cardiac MRI scan.
Timepoint [5] 411424 0
Changes from baseline determined at the 3 months post randomisation.
Secondary outcome [6] 448917 0
Clinically significant bleeding defined as presence of Bleeding Academic Research Consortium (BARC) type 2 bleeding or above
Timepoint [6] 448917 0
3 months post randomisation.
Secondary outcome [7] 448918 0
Health care resource use and cost-effectiveness, as determined through analyses of re-hospitalisations and other follow-up data collected during the 3-month treatment period.
Timepoint [7] 448918 0
3 months post randomisation.
Secondary outcome [8] 448919 0
Days from randomisation to hospital discharge for index admission as ascertained from hospital medical records.
Timepoint [8] 448919 0
3 months post randomisation.
Secondary outcome [9] 448920 0
Re-hospitalisations within 3 months (cardiovascular and non-cardiovascular, number of days in hospital)
Timepoint [9] 448920 0
3 months post randomisation.

Eligibility
Key inclusion criteria
Patients with a new diagnosis of left ventricular (LV) thrombus on any imaging modality within the previous 10 days. Patients can be included if diagnosed with LV mural thrombus after acute MI, with ischemic cardiomyopathy or cardiomyopathy from other causes.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Conditions where either warfarin or a DOAC or both are contraindicated or a specific anticoagulant type is strongly recommended (for example, a mechanical heart valve, atrial fibrillation with moderate or severe mitral stenosis, severe renal dysfunction [Cockcroft-Gault creatinine clearance <30mL/min or end- stage renal disease], severe hepatic dysfunction [Child-Pugh Grade C], clinically significant active bleeding or intra-cranial haemorrhage in the prior 6 months)

In addition, pregnant or lactating women or women of childbearing potential, those with Takotsubo cardiomyopathy or those deemed likely to be non-adherent to the study medication or protocol will be excluded.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Treatment allocation is concealed by randomisation by a computer database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation). Randomisation is stratified by cardiac diagnosis (acute myocardial infarction within past 4 weeks versus no acute MI in past 4 weeks).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Reported rates of LV thrombus resolution range from approximately 50% to 90% of patients following acute MI, with the majority resolving within the first few weeks. In a meta-analysis of recent studies that have compared echocardiography with CMR, resolution rates at 3-6 months were 88%. Clinical events (cardiovascular death, stroke and systemic embolism) are key indicators of efficacy and important components of the composite primary endpoint. They are, however, relatively rare among contemporary patients receiving OAC therapy (~5-10% at 3 months), and are likely to occur more often in patients with persisting thrombus. Likewise, although clinically relevant bleeding events are reported to be approximately 20% lower in patients receiving DOACs, compared to those treated with warfarin, the absolute incidence over 3 months is expected to be low. Thus, if we assume a 76% “success rate” (i.e 76% of participants do not die from cardiovascular causes and have resolution of LV thrombus with no stroke, systemic embolization or clinically significant bleeding) in warfarin treated patients and 82% in those randomised to a DOAC then 204 participants are required to be 80% sure that the upper limit of a one-sided 97.5% confidence interval (or equivalently a 95% two-sided confidence interval [CI])) will exclude a difference in favour of the standard group (warfarin) of more than 10%. Assuming a loss to follow-up of 5%, 216 patients will be recruited into the trial.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/09/2018
Actual
25/10/2018
Date of last participant enrolment
Anticipated
30/06/2026
Actual
Date of last data collection
Anticipated
30/06/2029
Actual
Sample size
Target
216
Accrual to date
152
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 22658 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 22659 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 22660 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 22661 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 26764 0
The Northern Hospital - Epping
Recruitment hospital [6] 26765 0
Wollongong Hospital - Wollongong
Recruitment hospital [7] 26766 0
Westmead Hospital - Westmead
Recruitment hospital [8] 26767 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [9] 28131 0
Gosford Hospital - Gosford
Recruitment hospital [10] 28132 0
Prince of Wales Hospital - Randwick
Recruitment hospital [11] 28133 0
Ipswich Hospital - Ipswich
Recruitment postcode(s) [1] 37935 0
6000 - Perth
Recruitment postcode(s) [2] 37936 0
2139 - Concord
Recruitment postcode(s) [3] 37937 0
2170 - Liverpool
Recruitment postcode(s) [4] 37938 0
5042 - Bedford Park
Recruitment postcode(s) [5] 42814 0
3076 - Epping
Recruitment postcode(s) [6] 42815 0
2500 - Wollongong
Recruitment postcode(s) [7] 42816 0
2145 - Westmead
Recruitment postcode(s) [8] 42817 0
6150 - Murdoch
Recruitment postcode(s) [9] 44337 0
2250 - Gosford
Recruitment postcode(s) [10] 44338 0
2031 - Randwick
Recruitment postcode(s) [11] 44339 0
4305 - Ipswich
Recruitment outside Australia
Country [1] 10673 0
New Zealand
State/province [1] 10673 0
Auckland (Auckland Region); Waikato (Waikato Region); Christchurch (Canterbury Region); Whangarei (Northland Region); Dunedin (Otago Region)

Funding & Sponsors
Funding source category [1] 300190 0
Charities/Societies/Foundations
Name [1] 300190 0
Greenlane Research and Education Fund
Country [1] 300190 0
New Zealand
Funding source category [2] 311745 0
Charities/Societies/Foundations
Name [2] 311745 0
Heart Foundation (Australia)
Country [2] 311745 0
Australia
Primary sponsor type
Hospital
Name
Auckland District Health Board
Address
Park Rd,Grafton
Auckland, 1030
Country
New Zealand
Secondary sponsor category [1] 313205 0
University
Name [1] 313205 0
The University of Western Australia
Address [1] 313205 0
35 Stirling Highway, Crawley WA 6009
Country [1] 313205 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301021 0
Southern health and disability ethics committee
Ethics committee address [1] 301021 0
Ethics committee country [1] 301021 0
New Zealand
Date submitted for ethics approval [1] 301021 0
03/08/2018
Approval date [1] 301021 0
02/10/2018
Ethics approval number [1] 301021 0
Ethics committee name [2] 311189 0
WA Health Central HREC
Ethics committee address [2] 311189 0
Ethics committee country [2] 311189 0
Australia
Date submitted for ethics approval [2] 311189 0
05/04/2021
Approval date [2] 311189 0
07/07/2021
Ethics approval number [2] 311189 0
RGS0000004705

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85618 0
Prof Ralph Stewart
Address 85618 0
Cardiology Department Level 3 Auckland City Hospital Park Rd Grafton Auckland 1030
Country 85618 0
New Zealand
Phone 85618 0
+64 21 2287458
Fax 85618 0
Email 85618 0
[email protected]
Contact person for public queries
Name 85619 0
Ralph Stewart
Address 85619 0
Cardiology Department Level 3 Auckland City Hospital Park Rd Grafton Auckland 1030
Country 85619 0
New Zealand
Phone 85619 0
+64 21 2287458
Fax 85619 0
Email 85619 0
[email protected]
Contact person for scientific queries
Name 85620 0
Ralph Stewart
Address 85620 0
Cardiology Department Level 3 Auckland City Hospital Park Rd Grafton Auckland 1030
Country 85620 0
New Zealand
Phone 85620 0
+64 21 2287458
Fax 85620 0
Email 85620 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: this is not stipulated in consent form



What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.