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Trial registered on ANZCTR


Registration number
ACTRN12614000042640
Ethics application status
Approved
Date submitted
7/01/2014
Date registered
16/01/2014
Date last updated
5/11/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
PROTECT-ICD Trial: Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator (ICD) Implantation to Prevent Tachyarrhythmias following Acute Myocardial Infarction
Scientific title
PROTECT-ICD Trial: A study targeting prevention of sudden cardiac death in patients who have reduced cardiac function following a myocardial infarct by assessing whether electrophysiologic study to guide prophylactic implantation of an implantable cardioverter-defibrillator (ICD) early following myocardial infarction (first 40 days) will lead to a significant reduction in sudden cardiac death.
Secondary ID [1] 283602 0
None
Universal Trial Number (UTN)
U1111-1150-3865
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sudden cardiac death 290524 0
Condition category
Condition code
Cardiovascular 290914 290914 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention group all undergo electrophysiologic study early after myocardial infarction (within 40 days of MI). The electrophysiology study is done in a hospital laboratory by a specialist cardiologist under local anaesthetic and sedation given through a cannula. A sheath will be placed into the vein in the groin. The Cardiologist will then place 2 electrode catheters into the heart with the use of x-ray images to carefully guide the catheters into the proper areas. The electrode catheters will be used to stimulate the heart and record the electrical activity. This test will take approximately one hour. The patient will generally stay overnight in hospital and go home the next day.
If the study is positive (inducible monomorphic ventricular tachycardia of cycle length less than or equal to 200ms) participants have an ICD implanted. Participants with a negative study (no inducible arrhythmia or induced ventricular fibrillation/ ventricular flutter cycle length <200ms) are discharged without an ICD.
Implantation of an ICD device involves positioning leads in the heart and placing a box device under the skin, usually in the shoulder area. The procedure is done in a hospital laboratory by a specialist cardiologist under local anaesthetic and with sedation through an intravenous cannula. The leads are inserted through a small incision, usually near the collarbone. X-ray images are used to guide the lead/s into the heart. These leads are attached to the device box which is then placed just beneath the skin and the incision closed with stitches. The patient will often stay overnight in hospital and go home the next day. The device remains in situ for the remainder of the patient's life, barring any complications that would require it's removal.

At select centres a proportion of trial patients at >48 hours following revascularisation for myocardial infarction will also undergo cardiac magnetic resonance imaging (CMR). This is a non-invasive painless test which does not involve any radiation. A series of images will be taken of the heart while positioned on a moveable examination table. The test will take 30-45 minutes and in most cases will involve injection of a contrast material into an intravenous line.
Intervention code [1] 288290 0
Early detection / Screening
Intervention code [2] 288578 0
Prevention
Intervention code [3] 288579 0
Treatment: Devices
Comparator / control treatment
The control group receive ongoing standard care according to the practise of their institution. This includes discharge from hospital as per their treating physician and follow up as usual in the community. Participants in this group would be eligible to receive an ICD according to the standard practise of their cardiologist (guideline recommendations are after 40 days following myocardial infarction or 90 days following revascularisation only in patients with left ventricular ejection fraction less than or equal to 30% or less than or equal to 35% in the presence of heart failure).
Control group
Active

Outcomes
Primary outcome [1] 290902 0
The primary outcome will be a combined endpoint of non-fatal arrhythmia and sudden cardiac death. Non-fatal arrhythmia includes resuscitated cardiac arrest, sustained ventricular tachycardia and ventricular fibrillation in participants without an ICD.
Timepoint [1] 290902 0
At 2 years after randomisation.
Secondary outcome [1] 305570 0
All cause mortality. Assessed by patient follow up and review of clinical files and data. Adjudicated by an independent core lab/committee.
Timepoint [1] 305570 0
At 2 years after randomisation.
Secondary outcome [2] 306326 0
Non-sudden cardiovascular death. Assessed by patient follow up and review of clinical files and data. Adjudicated by an independent core lab/committee.
Timepoint [2] 306326 0
At 2 years after randomisation.
Secondary outcome [3] 306327 0
Non-fatal repeat MI. Assessed by patient follow up and review of clinical files and data.
Timepoint [3] 306327 0
At 2 years after randomisation.
Secondary outcome [4] 306328 0
Heart failure. Assessed by patient follow up and review of clinical files and data.
Timepoint [4] 306328 0
At 2 years after randomisation.
Secondary outcome [5] 306329 0
In patients with an ICD, secondary outcomes will include appropriate and inappropriate ICD activations. Assessed by patient follow up and review of clinical files and data. Adjudicated by an independent core lab/committee.
Timepoint [5] 306329 0
At 2 years after randomisation.
Secondary outcome [6] 306330 0
In patients with an ICD, secondary outcomes will include complications or re-hospitalisation associated with ICD implantation. Complications may include death related to implantation, pneumothorax following procedure, significant bleeding or hematoma related to procedure, lead or box infection, wound infection, lead revision or failure. Assessed by patient follow up and review of clinical files and data.
Timepoint [6] 306330 0
At 2 years after randomisation
Secondary outcome [7] 306332 0
CMR images will be reviewed and the infarct zone will be quantified for each patient and correlated with:
* Presence or absence of inducible ventricular tachycardia at electrophysiology study
* Combined endpoint of appropriate ICD activation or sudden cardiac death and non-fatal arrhythmia at follow up.
Assessed by patient follow up and review of clinical files and data. Adjudicated by an independent core lab/committee.
Timepoint [7] 306332 0
At 2 years after randomisation

Eligibility
Key inclusion criteria
Participants will be 2-40 days (inclusive) following a myocardial infarct, with impaired left ventricular systolic function (Left Ventricular Ejection Fraction <=40% or at least moderately impaired).
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnancy;
* Nursing home resident dependent on one or more activities of daily living;
* Significant non-cardiac co-morbidity with high likelihood of death within 1 year;
* Significant psychiatric illnesses that may be aggravated by device implantation or that may preclude regular follow up;
* Intravenous drug abuse (ongoing);
* Unresolved infection associated with risk for hematogenous seeding;
* Pre-existing implantable cardioverter-defibrillator (ICD);
* Secondary prevention indication for an ICD (i.e. sustained ventricular arrhythmias occurring more than 48 hours after qualifying myocardial infarction);
* On the heart transplant list;
* Recurrent unstable angina despite revascularisation (defined as ongoing chest pain or ischemic symptoms at rest or with minimal exertion despite adequate treatment with anti-anginal medications);
* Congestive heart failure New York Heart Association class IV, defined as shortness of breath at rest, which is refractory to medical treatment (not responding to treatment)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed at the time of enrolling a subject.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by the electronic data capture database
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
In the study cohort it is anticipated that early (first 40 days) sudden cardiac death / non-fatal arrhythmia occurs in 5.4% and late (40 days to 2 years) sudden deaths / non-fatal arrhythmia occur in 1.3% of surviving patients. It is also assumed that a proportion of events will not be prevented in the intervention arm due to 30% of sudden deaths being due to non-arrhythmic causes, and 13% occurring in EPS negative patients. It is anticipated that a 2 year primary event rate of 6.7% in the control arm will be reduced to 2.8% in the intervention arm. A two group chi-squared test with a 0.05 two-sided significance level will have 80% power to detect the difference between a Group 1 proportion of 0.028 experiencing the primary endpoint and a Group 2 proportion of 0.067 experiencing the primary endpoint when the sample size in each group is 470. Allowing 2% crossover and 10% loss to follow up the required sample size is 1,058 (529 patients per arm).

The primary endpoint will be analysed using the Kaplan-Meier estimator with log-rank tests used to compare the occurrence of the primary outcome between the intervention and control groups.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 1720 0
Westmead Hospital - Westmead
Recruitment hospital [2] 1721 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 1722 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 1723 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [5] 1724 0
Nepean Hospital - Kingswood
Recruitment hospital [6] 1725 0
St George Hospital - Kogarah
Recruitment hospital [7] 1726 0
Gosford Hospital - Gosford
Recruitment hospital [8] 1727 0
Eastern Heart Clinic - Randwick
Recruitment hospital [9] 1728 0
Wollongong Hospital - Wollongong
Recruitment hospital [10] 1729 0
Blacktown Hospital - Blacktown
Recruitment hospital [11] 1730 0
The Prince Charles Hospital - Chermside
Recruitment hospital [12] 1731 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [13] 1732 0
Gold Coast Hospital - Southport
Recruitment hospital [14] 1733 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [15] 1734 0
John Flynn - Gold Coast Private Hospital - Tugun
Recruitment hospital [16] 1735 0
The Townsville Hospital - Douglas
Recruitment hospital [17] 1736 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [18] 1737 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [19] 1738 0
The Northern Hospital - Epping
Recruitment hospital [20] 1739 0
The Alfred - Prahran
Recruitment hospital [21] 1740 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [22] 1741 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [23] 1742 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [24] 1743 0
Royal Perth Hospital - Perth
Recruitment hospital [25] 1744 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [26] 1745 0
Fremantle Hospital and Health Service - Fremantle
Recruitment hospital [27] 1746 0
The Canberra Hospital - Garran
Recruitment outside Australia
Country [1] 5630 0
New Zealand
State/province [1] 5630 0
Wellington
Country [2] 5631 0
New Zealand
State/province [2] 5631 0
Hamilton
Country [3] 5632 0
New Zealand
State/province [3] 5632 0
Christchurch
Country [4] 5634 0
New Zealand
State/province [4] 5634 0
Auckland

Funding & Sponsors
Funding source category [1] 288282 0
Commercial sector/Industry
Name [1] 288282 0
BIOTRONIK Australia
Address [1] 288282 0
Suite 2, Level 4, Building 2
20 Bridge Street,
Pymble NSW 2073
Country [1] 288282 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Western Sydney Local Health District
Address
Western Sydney Local Health District
Cnr Darcy and Hawkesbury Rd
Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 287000 0
None
Name [1] 287000 0
Address [1] 287000 0
Country [1] 287000 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290178 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 290178 0
Research Office
Room 1072, Level 1, Education Block
Westmead Hospital, Hawkesbury and Darcy Roads
Westmead NSW 2145
Ethics committee country [1] 290178 0
Australia
Date submitted for ethics approval [1] 290178 0
28/06/2012
Approval date [1] 290178 0
12/11/2012
Ethics approval number [1] 290178 0
HREC2012/8/4.5(3572) AU RED HREC/12/WMEAD/277

Summary
Brief summary
The PROTECT-ICD study is a multi-centre randomised controlled trial targeting prevention of sudden cardiac death in patients who have reduced cardiac function following a myocardial infarct. The primary objective of the trial is to assess whether electrophysiologic study to guide prophylactic implantation of an implantable cardioverter-defibrillator early following MI (first 40 days) will lead to a significant reduction in sudden cardiac death. The secondary objective is to assess the utility of cardiac magnetic resonance imaging in assessing early myocardial viability, and its predictive value for both inducible and spontaneous ventricular tachyarrhythmias post-myocardial infarction.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44366 0
A/Prof Pramesh Kovoor
Address 44366 0
Cardiology Department
Level 2, Westmead Hospital
Cnr Darcy and Hawkesbury Rd
Westmead NSW 2145
Country 44366 0
Australia
Phone 44366 0
+61 2 9845 6030
Fax 44366 0
Email 44366 0
pramesh.kovoor@sydney.edu.au
Contact person for public queries
Name 44367 0
Mrs Jackie Hoynes
Address 44367 0
Cardiology Department
Level 2, Westmead Hospital
Cnr Darcy and Hawkesbury Rd
Westmead NSW 2145
Country 44367 0
Australia
Phone 44367 0
+61 2 9845 8509
Fax 44367 0
Email 44367 0
jhoynes@georgeinstitute.org.au
Contact person for scientific queries
Name 44368 0
A/Prof Pramesh Kovoor
Address 44368 0
Cardiology Department
Level 2, Westmead Hospital
Cnr Darcy and Hawkesbury Rd
Westmead NSW 2145
Country 44368 0
Australia
Phone 44368 0
+61 2 9845 6030
Fax 44368 0
Email 44368 0
pramesh.kovoor@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
No Results