Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02513030 |
| Other study ID # |
SHEBA-15-2033-MG-CTIL |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
March 5, 2015 |
| Last updated |
October 18, 2017 |
| Start date |
August 2015 |
| Est. completion date |
October 2018 |
Study information
| Verified date |
October 2017 |
| Source |
Sheba Medical Center |
| Contact |
Michael Glikson, MD |
| Phone |
972-3-530-5330 |
| Email |
michael.glikson[@]sheba.health.gov.il |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The SIMPLE study was a large one, and lasted quite a few years due to its design as a
randomized controlled trial and the follow up needed to reach an endpoint. The investigators
aim to conduct an observational pilot study looking at frequency of positive findings during
VF testing . The comparator will be the rate of findings during testing in the Simple trial.
If the investigators will find an increased rate of findings (significantly higher than in
the Simple trial ) it may set the stage for a randomized controlled trial of replacements ,
along the line of the Simple trial , or to a recommendation to continue VF testing in all ICD
replacements.
Description:
Background: The need for intraoperative defibrillation testing (DT) during implant and/ or
replacement of implantable cardioverter-defibrillators (ICDs) is still in debate. The primary
assumption of intra-operative DT is that successful defibrillation at the time of implant
will predict successful treatment of clinical ventricular arrhythmias. However, the utility
of this long standing practice in an era of modern very efficient ICD systems has recently
been questioned. DT has not been proven to improve clinical outcomes, the relevance of test
shocks to clinical shocks was questioned, and the probabilistic nature of successful shocks
emphasized. Furthermore, testing may increase the risk, complexity and cost of ICD implants.
This issue was addressed by the recent Shockless IMPLant Evaluation (SIMPLE) study. The trial
demonstrated that routine defibrillation testing at the time of ICD implant was safe, but did
not improve shock efficacy or reduce mortality compared to the no-testing strategy. It is
therefore expected that the results of the SIMPLE trial will lead to a significant reduction
or abandonment of the practice of VF testing at the time of initial ICD implant.
Nevertheless induction of VF for testing purposes (VFT) may still have an important role in
selective populations that are at risk for defibrillation failure , who were not included in
the SIMPLE study . One such population is of those who undergo device replacements. Whereas
testing during replacement is seldom done , it is conceivable that this testing is going to
have a much higher yield that during initial implantations . In fact, results from the
Canadian ICD registry demonstrate a high rate of findings (up to 30%) when VF was induced
during device replacements. However, it is conceivable that since most patients did not
undergo testing, those were actually tested comprised a selected population with high
likelihood of failure .
Testing at time of replacement has the potential to uncover lead problems specifically but
not only in high voltage leads. Lovelock et al. have found that ICD generator replacement
dramatically increased the risk of subsequent Fidelis lead failure and that the majority of
these failures occurred within a matter of months after the procedure. Failure rates after
generator replacement of other recalled or non- recalled leads are not known. It is possible
that manipulation of the proximal portion of the lead during replacement or maybe clinically
silent lead defects that were present prior to the generator exchange and that surgical
manipulation accelerated the deterioration. Moreover, high energy shocks have been described
to expose insulation defects not previously discovered by low energy shocks and noninvasive
measurements.
Safety of DFT has also been a concern. The primary complications related to DT include:
systemic embolism from intra-cardiac thrombus, prolonged post-DT hypotension and
electro-mechanical dissociation, myocardial infarction, heart failure, cerebral anoxia, need
for intubation, prolonged anesthesia, chest compressions and complications from anesthesia.
The only large study to date which specifically evaluated this concern is the SIMPLE study.
The primary safety endpoint, comprised of complications within 30 days of the implant, was
also similar between the two patient groups (5.4 per cent )in the no-DT group vs. 6.5 per
cent in the routine DT group, p=0.25). Thus, despite questions regarding the need for routine
defibrillation testing, it is at least generally safe and may still be suitable for certain
patients at the physician's discretion.
The SIMPLE study was a large one, and lasted quite a few years due to its design as a
randomized controlled trial and the follow up needed to reach an endpoint. The investigators
aim to conduct an observational pilot study looking at frequency of positive findings during
VF testing . The comparator will be the rate of findings during testing in the Simple trial.
If the investigators will find an increased rate of findings (significantly higher than in
the Simple trial ) it may set the stage for a randomized controlled trial of replacements ,
along the line of the Simple trial , or to a recommendation to continue VF testing in all ICD
replacements.
Study Objective:
The investigators plan to evaluate the rates of the following outcomes in subjects undergoing
device replacement:
1. Failed DT
2. System malfunctions requiring intervention
3. Complications associated with DT during pocket generator change Secondary goals will
include assessment of device longevity, specific ICD lead model performance ,
defibrillation efficacy, complications, association between replacement surgical
techniques (i.e capsulectomy, electrosurgery settings and etc.) , data on lead
management if failure was identified (adding a new lead, extraction and etc.) and rate
of infection (i.e. association with type of antibiotics, IV vs PO, use of same pouch and
etc.) The primary endpoint of this sub-study is a composite of procedure related
complications including: 30-day procedure related infection, major bleeding ( (i.e
prolonging hospital stay, reguiring intervention or PC units) new electrode dysfunction.
Study design:
This will be a prospective observational multi-center study of DF testing in all patients
undergoing device replacement in the participating centers. All centers will follow the same
DF testing protocol whereas management of positive findings will be at the discretion of the
treating physicians, as will be the programming of devices following testing.
Primary Endpoint:
Demonstrate that the event rate of the primary outcome (defined as failure of DT at a single
shock at 10 J below maximal capacity of the device
Secondary Endpoints:
The investigators plan to assess the following outcomes and determine independent predictors
for their occurrence:
1. Rate of system malfunction requiring intervention
2. Complications associated with DT during pocket generator change.
3. Device longevity and specific ICD lead model performance
4. Lead management decisions in cases where lead failure is identified (adding a new lead,
extraction and etc.)
5. Procedure related infections and opted management (i.e. association with type of
antibiotics, IV vs. PO, use of same pouch and etc.)
6. Association between surgical replacement techniques (i.e capsulectomy, electrosurgery
settings and etc.) and pre-specified complication rate
Patients will undergo generator replacement according to local procedure standards of
practice. A minimum standard for VF evaluation will be a single shock at 10 J below maximal
capacity of the device. If unsuccessful investigators are encouraged to use any appropriate
method or testing to attain successful defibrillation. More extensive testing is permitted,
if investigators deem it necessary. Investigators are free to use any method of anesthesia
and patient monitoring that they feel is appropriate. All details of the operative procedure
including if total or partial capsulectomy was done, DT conducted, intra-operative
complications and device details will be captured at the time of implantation. The
investigators will also collect data on longevity of device (time from implantation to
replacement), use of antibiotics (IV and/or local, capsulectomy and use of plasma knife).
Operators are encouraged to a high-voltage impedance test within the normal range of the
device, to confirm the integrity of the high-voltage circuit in all patients. HV lead
impedance will be documented. In cases of SJM Riata leads fluoroscopy of the lead will be
done in LAO 30 and RAO 20 and documented.
VF testing : Patients will undergo induction of ventricular fibrillation (preferably Shock on
T but will be left to operator discretion)during the implant procedure. For this study, a one
shock at 10J below maximal device capacity will be programmed. If successful defibrillation
is not achieved , it is recommended that all reasonable efforts should be made to achieve
these criteria (i.e. addition of new lead/removal of coils or arrays, polarity reversal at
operator discretion) followed by repeat intra-operative testing. Testing shall be stopped
when the investigator deems that the likelihood of improving DFT by continued testing is
outweighed by the risks. A reason for stopping shall be documented. Test shock will be done
with new pocket generator and not old one.
Follow up: 6-monthly Follow-up visits: will include documentation of any peri-operative
complications. Patients will be also followed for clinical endpoints (occurrence of
appropriate shock, inappropriate shocks, lead failure, need for re- intervention and
infection). Study visits will coincide as much as possible with routine clinical visits,
allowing a flexibility of ± 1 month.
Patients will be followed at 6 monthly intervals until the last patient randomized has
received 6 months of follow up.
Contact information (family physician, next of kin) will be obtained at baseline, and these
individuals may be contacted during follow-up to ensure completeness of follow-up.
Sample Size Calculation: This is an observational study but in order to prove that
replacements carry a higher risk of significant findings compared to primary implantations
(as in the SIMPLE trial), the investigators will need 140 patients in order to detect an
absolute difference of 7% in the rate of the primary endpoint (failure to terminated induced
arrhythmia due to lead failure) with a power of 90% and 2-tailed alpha of 0.05 . This
calculation is based on the estimation of 10% primary endpoint event rate in this study
population that will be reported with a precision of ± 5%. Sample size calculation accounted
for 10% overall attrition rate.
Budget was calculated by assumption of 500$ per patient fee for the participating centers
plus study coordination and management costs.
The study will be managed by the Israeli Association for Cardiovascular Trials (IACT).
