Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001176954
Ethics application status
Approved
Date submitted
2/09/2020
Date registered
9/11/2020
Date last updated
9/11/2020
Date data sharing statement initially provided
9/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Code STORM: STandard care Or a Rapid early invasive Management approach to patients with life threatening heart rhythm disorders
Scientific title
Efficacy and Feasibility of Early Intervention with Catheter Ablation (CA) compared to anti-arrhythmic drugs (AADs) alone for Management of Ventricular Tachycardia (VT) storm
Secondary ID [1] 301114 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Code STORM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ventricular Tachycardia Storm 317208 0
Condition category
Condition code
Cardiovascular 315345 315345 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be expected to have a catheter ablation during their index hospital admission (preferably within 96 hours of presentation)

Medical therapy can be used as a temporising measure before catheter ablation, as is standard of care. If there is breakthrough VT during the period before the catheter ablation procedure, standard practice will be followed in stabilising the ventricular tachycardia (VT) including intravenous short acting anti-arrhythmic drugs (AADs) and internal or external cardioversion.

Catheter ablation procedures will be performed in the standard fashion, as described in the international guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death from the American Heart Association/American College of Cardiology/ Heart Rhythm Society and the expert consensus statement on Catheter Ablation of Ventricular Arrhythmias from Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society/Latin-America Heart Rhythm Society. Procedures will be performed under conscious sedation or general anaesthesia by a cardiologist trained in electrophysiology procedures and cardiac arrhythmia ablation. Ablation will be guided by a combination of mapping techniques, as per standard practice, and described in the guidelines for catheter ablation for VT. Mapping techniques will incorporate electro-anatomic substrate mapping, pace mapping, entrainment mapping and activation mapping where haemodynamically tolerated. The expected procedure duration will be between 3-6hrs. The procedural endpoints will be elimination of all clinical and inducible ventricular arrhythmias, as is standard practice, published in the aforementioned international guidelines. Repeat ablation procedures, if necessary, are permitted during the 48 hour blanking period after initiation of therapy.

Post procedure, AAD is stopped if the patient was drug naïve before randomisation. The baseline type and dose of AAD pre-randomisation is continued if the patient was on an AAD pre-randomisation.
Intervention code [1] 317426 0
Treatment: Other
Comparator / control treatment
Patients managed with anti-arrhythmic drugs (AADs) alone will follow a protocol aligned with standard clinical care/current clinical guidelines, the objective being that the control arm replicates what would constitute standard of care for patients with ventricular tachycardia storm managed with a non-interventional approach.

For participants randomised to the control group, their clinician will be referred to current protocols of care and published guidelines for acute management of VT storm. A specific protocol for AAD will not be mandated. In general, however, this includes emergent treatment with intravenous amiodarone, with intravenous beta-blockade and intravenous lignocaine for additional control followed by transition to oral AADs as tolerated. Doses of all treating medications (including amiodarone) prescribed will be left to the treating clinician's discretion. If all of the above do not control VT, the AAD drug treatment is generally deemed to have failed.

Clinicians may consider alternative antiarrhythmic if there is a contraindication. For example, patients intolerant of beta-blockers may be commenced on a dihydropyridine calcium channel blocker such as verapamil or diltiazem. Antiarrhythmic dosing can be up titrated to the maximal tolerated amount as decided by the treating clinician.

Similar to the intervention arm, there will be a 48 hour blanking period after initiation of therapy to allow sufficient time for AAD therapy in the control arm to be established.

If their treating clinician during the time-course of the trial decides to do a catheter ablation for VT storm, the occurrence and time point of this cross-over will be recorded. Cross-over is estimated to be <2% as per the Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease (VANISH) trial.
Control group
Active

Outcomes
Primary outcome [1] 323603 0
VT recurrence ascertained by either an implanted cardioverter defibrillator (ICD) which most patients will have prior to hospital discharge. In patients in whom an ICD implant is not indicated due to the absence of structural heart disease, periodic multi-day Holter monitoring or loop recorder implant (5-7 days) will be used at pre-defined time points.

VT recurrence is defined as VT identified and treated by the ICD with anti-tachycardia pacing (ATP) and/or internal ICD delivered shock or >=30 seconds of VT if untreated by ICD. If VT events occur prior to ICD implantation, 24-hour continuous telemetry monitoring will be used to confirm events.
Timepoint [1] 323603 0
The primary endpoint is assessed by ICD transmission by remote monitoring and/or scheduled ICD interrogations or multi-day Holter monitor during follow-up.
Follow-ups will occur at pre-defined time points of 6 weeks, then 3, 6, 12, 18, 24, 30 and 36 months post randomisation (Median 18 months)
Secondary outcome [1] 382333 0
All cause Mortality as a composite of
a. Cardiac death
b. Non-cardiac death

Data collected from medical records and during patient follow up over trial period
Timepoint [1] 382333 0
Follow-ups will occur at pre-defined time points of 6 weeks, then 3, 6, 12, 18, 24, 30 and 36 months post randomisation (Median 18 months)
Secondary outcome [2] 382334 0
Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI) as a composite of
a. AESI related to effects of catheter ablation - any adverse event that, in the investigator’s and cardiologist opinion, is a complication of the catheter ablation procedure and occurs within 48 hours of catheter insertion while the patient is in hospital. This will be decided through clinical assessment by the treating cardiologist.
b. AESI related to medical anti-arrhythmic drug therapy - symptoms reported via the patient via phone or in-clinic. Drug toxicity noted via biomarkers using serum assay of liver function test and thyroid function test. Renal function will also be measured.
Timepoint [2] 382334 0
Follow-ups will occur at pre-defined time points of 6 weeks, then 3, 6, 12, 18, 24, 30 and 36 months post randomisation (Median 18 months)
Secondary outcome [3] 382340 0
VT storm (three or more documented episodes of ventricular tachycardia within 24 hours or incessant VT); assessed through home monitoring (online transmissions via implanted device), medical records, hospital admissions and other records linked into the hospital system, patient reporting of symptoms and therefore being brought in for follow-up of their device.
Timepoint [3] 382340 0
Follow-ups will occur at pre-defined time points of 6 weeks, then 3, 6, 12, 18, 24, 30 and 36 months post randomisation (Median 18 months)
Secondary outcome [4] 382341 0
VT burden (number of episodes of VT in the preceding 6 months compared to the 6 months after randomisation and therapy); measured by home monitoring device recording transmissions from a patients implanted defibrillator.
For patients without a defibrillator, VT burden will be ascertained by periodic multi-day Holter monitor at pre-defined timepoints.
Timepoint [4] 382341 0
Follow-ups will occur at pre-defined time points of 6 weeks, then 3, 6, 12, 18, 24, 30 and 36 months post randomisation (Median 18 months)
Secondary outcome [5] 382342 0
Length of hospital stay (Days in hospital from index admission for VT storm). This information will be extracted from the patient's medical records.
Timepoint [5] 382342 0
At time of discharge following index hospital admission
Secondary outcome [6] 382343 0
Cardiovascular hospitalisation (all cause, including stroke, syncope, heart failure and hospitalisation for arrhythmia), monitored via hospital admissions and/or medical records
Timepoint [6] 382343 0
Follow-ups will occur at pre-defined time points of 6 weeks, then 3, 6, 12, 18, 24, 30 and 36 months post randomisation (Median 18 months)
Secondary outcome [7] 382348 0
Cost effectiveness of catheter ablation compared to medical care (measures include costs of inpatient hospital treatment during the index admission, outpatient clinic and emergency department visits during the follow up period, disposal equipment used (including catheters), total costs of catheter ablation (equipment and personnel), recurrent hospitalisations due to VT, cost of anti-arrhythmic medications).
Data linkage of participants via the NSW Centre for Health Record Linkage (CHeReL) and PBS/MBS data through Australian Institute of Health and Welfare (AIHW), will be used to estimate the resource use associated with treating this patient cohort.
Timepoint [7] 382348 0
Follow-ups will occur at pre-defined time points of 6 weeks, then 3, 6, 12, 18, 24, 30 and 36 months post randomisation (Median 18 months)

Eligibility
Key inclusion criteria
Patients will be eligible for inclusion if they have/are:
1. Age greater than or equal to 18 years;
2. VT storm due to sustained monomorphic VT (MMVT), confirmed on 12-lead ECG or implanted cardiac device which may include an implanted cardioverter defibrillator (ICD), cardiac pacemaker, loop recorder, cardiac resynchronisation therapy device or detected on a Holter monitor or during an exercise stress test;
3. Patients with VT storm defined as incessant VT or 3 or more isolated episodes of VT appropriately treated by their ICD or VT requiring external or pharmacological attempts at reversion to the patient’s baseline rhythm;
4. Informed consent able to be provided to be in the trial
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they have/are:
1. Concomitant illness, physical impairment or mental condition which in the opinion of the study team/primary care physician could interfere with the conduct of the study including outcome assessments;
2. Pregnant and/or breastfeeding
3. Unable or unwilling to provide informed consent
4. Unable or unwilling to complete study procedures or attend clinic follow up

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)
There will be allocation concealment.
Each participant will be assigned with a randomisation number generated from a central, secure, password-protected web portal (Redcap). The trial investigator enrolling participants into the study will not know in advance which treatment the participant will be randomised to.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of eligible participants will be 1:1 to intervention and control arms, and will be performed using a secure, password-protected web portal (Redcap) that can perform computerised sequence generation.

The randomisation allocation will be open to all participants, study team members, and the primary study statistician.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features

Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size calculations
Published data on VT storm recurrence with anti-arrhythmic drug (AAD) use alone is between 50-81% at 1 year; in the absence of specific data on recurrence of any VT after an episode of VT storm, we anticipated that recurrence of any VT would be higher than the rate of recurrence of VT storm. Hence, we used a conservative estimate of 60% VT recurrence at ~18 months for the control arm. In a meta-analysis of all published studies on efficacy of ablation for the treatment of VT storm, the recurrence of VT storm after ablation is estimated to be 6% at ~1 year. Assuming a VT storm recurrence rate of 60% with AAD at 18 months, and a relative risk reduction of 40% (RR 0.6) with intervention compared with usual care (both being conservative estimates of endpoints), with power 80%, 2-sided significance, P<0.05 and ~10% dropout, we estimate that 150 patients (75 in each arm) will be required.

Statistical data analysis
All data analysis will be performed by a statistician independent of the study investigators. Analyses of study outcomes will be conducted according to the principle of intention-to-treat. The primary and secondary outcomes will be summarised with the use of Kaplan-Meier estimates and compared with the use of nonparametric log-rank tests. Cox-proportional hazards models will be calculated and used to test for interactions in subgroups. For reporting of baseline characteristics continuous variables will be reported as means and standard deviations, or medians and interquartile ranges and tested with the use of the t-test, or the Wilcoxon-Mann-Whitney tests, as appropriate; categorical variables will be compared using the Fisher’s exact test. All data will be entered into a pre-designed database in consultation with a statistician and enabling statistical monitoring. Patient reported outcomes will be compared between treatment groups using analysis of covariance where the baseline level will be included in linear or logistic regression models as relevant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2020
Actual
Date of last participant enrolment
Anticipated
30/11/2023
Actual
Date of last data collection
Anticipated
30/11/2026
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 16558 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 30121 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 305558 0
Other
Name [1] 305558 0
Perpetual Ramaciotti Health Investment Grant
Country [1] 305558 0
Australia
Funding source category [2] 305565 0
Government body
Name [2] 305565 0
NSW Health Cardiovascular Research Capacity Program Grant
Country [2] 305565 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
Westmead Public Hospital,
Cnr Darcy and Hawkesbury Roads,
Westmead, NSW, 2145
Country
Australia
Secondary sponsor category [1] 305971 0
None
Name [1] 305971 0
Address [1] 305971 0
Country [1] 305971 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305864 0
Western Sydney Local Health District (WSLHD) HREC
Ethics committee address [1] 305864 0
Ethics committee country [1] 305864 0
Australia
Date submitted for ethics approval [1] 305864 0
11/03/2020
Approval date [1] 305864 0
13/07/2020
Ethics approval number [1] 305864 0

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

Contacts
Principal investigator
Name 101854 0
A/Prof Saurabh Kumar
Address 101854 0
Westmead Hospital
Hawkesbury and Darcy Roads
Westmead NSW 2145
Country 101854 0
Australia
Phone 101854 0
+61 2 8890 8140
Fax 101854 0
Email 101854 0
[email protected]
Contact person for public queries
Name 101855 0
Saurabh Kumar
Address 101855 0
Westmead Hospital
Hawkesbury and Darcy Roads
Westmead NSW 2145
Country 101855 0
Australia
Phone 101855 0
+61 2 8890 8140
Fax 101855 0
Email 101855 0
[email protected]
Contact person for scientific queries
Name 101856 0
Saurabh Kumar
Address 101856 0
Westmead Hospital
Hawkesbury and Darcy Roads
Westmead NSW 2145
Country 101856 0
Australia
Phone 101856 0
+61 2 8890 8140
Fax 101856 0
Email 101856 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.