Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02493075 |
| Other study ID # |
IIs-304 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 1/Phase 2
|
| First received |
June 25, 2015 |
| Last updated |
July 8, 2015 |
| Start date |
March 2015 |
| Est. completion date |
June 2018 |
Study information
| Verified date |
July 2015 |
| Source |
Sir Run Run Shaw Hospital |
| Contact |
Chenyang Jiang, MD |
| Phone |
+86 13857190051 |
| Email |
jiangchenyang[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
China: Health and Family Planning Commission of Zhejiang Province |
| Study type |
Interventional
|
Clinical Trial Summary
The objective of the study is:Phase I: To validate or otherwise determine the
Chinese-specific appropriate contact force during PVI in PAF.Phase II: To evaluate the
effectiveness and safety of ablation guided by the appropriate contact force.
Description:
Background： Atrial fibrillation (AF) is a major cause of substantial mortality and morbidity
from thromboembolism, heart failure (HF), and cognitive dysfunction. With the aging of the
population and improved survival after myocardial infarction and HF, AF is emerging as a
major public health concern.
Recently, significant progress has been made in treatment of AF with catheter ablation,
emerging as an increasingly important technique. According to the current guidelines,
catheter ablation can be considered as the first-line treatment of choice for patients with
drug refractory paroxysmal AF (PAF). Circumferential PV isolation (CPVI) is a widely
accepted cornerstone of this procedure, but limited by an unacceptable recurrence rate,
mainly due to recovery of pulmonary vein (PV) conduction.
Durable, continuous, transmural isolation of PV is one of the most important goals of
radiofrequency catheter ablation (RFCA) for PAF. The contact force (CF) between the ablation
catheter and target tissue was considered closely related to the ablation effectiveness.
Appropriate CF should be able to generate enough tissue lesions, and avoid the
complications, such as cardiac perforation, atrial-esophageal fistula. Nowadays, irrigated
ablation catheters are widely used, but the CF is mostly dependent on operators' experience
and feeling, unable to be precisely measured. The tissue lesion produced would be variable
in different operators, and the learning curve would be time consuming.
The newly approved CF catheter enables measurement of catheter tip contact force and force
vector, providing the real-time CF during ablation. It would be helpful, not only for
effective lesions formation, but also for the prevention from complications.
Studies from Western-population indicated that higher long-term successful rate could be
achieved by using CF catheter, and CF between 10 to 20g was adopted in most centers. It
would be important to find the appropriate range of CF for Chinese populations, because of
various factors including for instance thinner and smaller atrial chambers among Chinese.
Objectives Phase I: To validate or otherwise determine the Chinese-specific appropriate CF
during PVI in PAF.
Phase II: To evaluate the effectiveness and safety of ablation guided by the appropriate CF
Trial design and Treatment of Subjects Phase I Instrument: CARTO™, Biosense Webster,
Electrophysiology（EP）recording system, Thermocool® SmartTouch™ Catheter，Lasso/Navi-Lasso
catheter, etc.
NO. of cases: 20 Study duration: 2 months Strategy：Circumferential pulmonary vein isolation
Procedure： Local anaesthesia, Sedation Catheters are advanced through the right/left femoral
vein. After double transseptal punctures, 8F or 8.5F SL1 Swartz sheath and Steerable sheath
(e.g. Agilis, St Jude) will be placed in left atrium (LA), followed by PVs' venography
Establishment of the anatomical model of LA and all PVs: Respiratory gating, Point-by-Point
or Fast Anatomical Mapping (FAM). When using Point-by-Point, CF would be controlled between
5 to 10g. When using FAM, the model around PVs would be adjusted by SmartTouch catheter with
CF 5-10g.
Parameter setting: Power-anterior wall 35W, posterior wall 30W; Irrigated flow rate =
17-30ml/min；Impendence - up to 170Ω； Operator: Dr. Chenyang Jiang Ablation catheter could be
moved if, electrical activity amplitude decrease >80%, impedance decrease >10Ω, or ablation
time more than 20s.
Endpoint: Bi-directional block between left atrial and pulmonary vein (LA-PV), and no
capture along CPVI line.
The operator will be blinded to CF data, which would be monitored by the assistant. When the
CF is higher than 40g, the operator will be warned.
Parameters: total procedure time, model reconstruction time, power, ablation time,
impedance, CF, force-time integral (FTI).
Introduction for PV ablation:
Perform circumferential PV ablation in the order.
1. When PV is isolated after circular linear ablation without touch-up ablation, 30min
waiting time + isoproterenol（ISP）/adenosine triphosphate（ATP） induction would be
performed to detect the acute reconnection. If there's no reconnection, each segment
will be identified as "isolated segment", and the ablation CF, time, FTI, and the power
of each segment will be recorded.
2. When PV isolated initially, but reconnected by 30min+ISP/ATP observation, re-isolation
would be performed, and the segment with conduction gaps(GAP) will be identified as
"acute reconnected segment(s)".
3. If PV isolation not achieved by initial circumferential ablation, additional ablation
along the circular lesion will be performed until PV isolated, and the segment(s)
re-ablated will be identified as "unisolated segment(s)", record the parameters.
30min+ISP/ATP detection will be performed after isolation, "isolated segment(s)" and
"acute reconnected segment(s)" will be identified, as described above in a. and b. If
the "acute reconnected segment(s)" is the same segment(s) as "unisolated segment(s)",
classify to the latter group.
Analysis for appropriate CF For each segment, single variable and multiple regression
analysis will be performed between the three groups ("isolated segment"," acute reconnected
segment ", and "unisolated segment"), to define an "appropriate CF". The sensitivity and
specificity of the "appropriate CF" will be analyzed.
Phase II:
Instrument: CARTO™, Biosense Webster, EP recording system, Thermocool® SmartTouch™
Catheter，Lasso/Navi-Lasso catheter, etc.
NO. of cases: 120 Study duration: enrollment - 12 months, follow-up - 12 months, Data
analysis and papers preparation - 3 months.
Strategy：Circumferential pulmonary vein isolation Patients will be randomized with 1:1 ratio
into one of the two following groups: "CF guided group" and "usual ablation group".
Procedure： The preparation, including anaesthesia, sedation, vascular access, transseptal
puncture, is the same as described in phase I.
CF guided group:
After the establishment of the anatomical model of LA and all PVs (the same as phase I),
ablation will be performed with the guidance of real-time CF, ablation time, FTI, etc. CF
will be controlled in the range of "appropriate CF", which has been defined in phase I.
Circumferential PV ablation will be performed orderly, "isolated segment"," acute
reconnected segment ", and "unisolated segment" will be also identified as described in
phase I.
Endpoint: bi-directional block between LA-PV, and no capture along CPVI line. Parameters
recording: total procedure time, model reconstruction time, power, ablation time, impedance,
CF, FTI.
Usual ablation group:
Operator will be blinded to CF data, the procedure performance is the same as described in
phase I.
Follow-up Warfarin or new oral anticoagulants will be administered to all patients for at
least 3months after the procedure. The international normalized ratio will be controlled
between 2.0 and 3.0 if warfarin prescribed.
After discharge, patients will be followed up at 1, 3, 6, 9, 12months post ablation.
Patients' experiences, 12-lead electrocardiograms (ECGs) and Holter monitoring (non-required
at 1, 9 months) will be recorded to evaluate recurrence at each appointment (not including 1
and 3 month visit post procedure) and any visits when the patient experience symptoms that
suggestive of arrhythmia. The first 3 months is considered as a blanking period.
Recurrence is defined as AF/flutter/tachycardia, lasting longer than 30s, that documented by
an ECG or Holter recording, or highly suggestive symptoms, after 3 months post-procedure.
Primary end point: Freedom from AF recurrence on the ECGs and Holter monitoring at each
visit during the period from 3 months to 1 years after procedure, independent of
antiarrhythmic drug(AAD) therapy.
Secondary end points: (1) Freedom from AF recurrence, dependent of AAD therapy; (2)Freedom
of arrhythmia-related symptoms; (3)Safety Outcomes, contain mortality (death overall and
procedure-related), vascular access complications (bleeding, hematoma, pseudoaneurysm,
arteriovenous fistula), periprocedural events (stroke, transient ischemic attack, cardiac
tamponade, pulmonary embolism, deep vein thrombosis, other embolism, LA-esophageal fistula,
Other fistula, pericardial effusion, PV stenosis, atrioventricular block, heart failure
exacerbation, need for a pacemaker, phrenic nerve injury, acute coronary artery occlusion,
valve injury).
Follow-up will terminate after a maximum follow-up period of 12 months. Data Management
Requirements for investigators on data entry The investigator ensures that data are entered
into the medical records and the Case Report Forms (CRFs) truthfully, precisely, completely,
timely and legally.
Information on all patients who signed the Informed Consent Form and enter the trial when
considered eligible through screening should be closely observed and recorded in the CRFs
without any field left blank or missing.
All data on the CRFs should be checked against the source records for consistency.
As source documents, the CRFs should be revised only by drawing a single line with the
investigator's signature and date of revision added.
Source laboratory test reports (or their copies) should be adhered to the field for adhering
laboratory test reports in the medical records.
Data that are significantly high or low or outside the clinically acceptable range should be
carefully verified and reviewed, and necessary explanations should be given by the
investigator.
Requirements for monitors on data monitoring The monitors should pay regular visits to the
sites to examine the status of signing of informed consent, screening and enrollment.
Ensure that all the CRFs are correctly filled out and are consistent with the source data.
Ensure that all the errors or missing data have been corrected or explained, and have been
signed and dated by the investigator.
Changes in treatment, concomitant medications, intercurrent conditions and ECG recording
should be confirmed and recorded for each subject.
Discontinuations and loss-to-follow-ups of each subject should be indicated in the CRFs.
Confirm that all the adverse events (AEs) have been filed. Establishment of database and
data entry Establishment of database：A study-specific database system will be established as
per the items on the CRF.
Data entry: Data will be entered concurrently by data managers through double entry.
Data review: Each data item should be verified and the discrepancies be reported. The source
forms should be verified on an item-by-item basis and the errors be corrected.
In case of any doubt during data entry, the data manager may fill out a Data Query Form
which will be returned to the monitor. When the investigator has resolved in writing the
queries in the query form and signed, the form will be sent back to the data managers. Data
Query Forms should be appropriately stored.Selection and withdrawal of subjects
Statistical analysis Phase I For each segment, single variable and multiple regression
analysis will be performed between the three groups ("isolated segment"," acute reconnected
segment ", and "unisolated segment"), to define an "appropriate CF". The sensitivity and
specificity of the "appropriate CF" will be analyzed.
Phase II Log-rank test will be used for inter-group comparison of recurrence. Kaplan-Meier
method will be used for the estimation of currency curves for all points. When considering
the central effects and the important prognostic factors, Cox proportional risk model will
be used to estimate the risks compared with blank with the confidence intervals.
More data for "initially-isolated segment", "initially- nonisolated segment", and
"additionally-isolated segment" will be collected, and the "appropriated CF" will be
re-analyzed.
