Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06156670 |
| Other study ID # |
27112023 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2023 |
| Est. completion date |
March 2025 |
Study information
| Verified date |
November 2023 |
| Source |
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The study will include all patients over 18 years of age who underwent endovascular closure
of patent foramen ovale in medical centers in the Russian Federation, who gave written
informed consent to the closure and provided personal data as part of inpatient medical care.
The project participants will be 29 medical centers in the Russian Federation, where
endovascular closure of patent foramen ovale is performed.
Description:
Ischemic stroke is the fifth most common cause of death and the leading cause of disability
among adult patients worldwide. Cryptogenic stroke is a very broad term that applies in cases
of incomplete evaluation, with multiple "competing" causes, and in situations where the cause
could not be identified during evaluation. This type of stroke has been termed embolic stroke
from an undetermined source, or ESUS (Embolic Stroke of Undetermined Source). Possible causes
of ESUS include cardiopathies, including isolated atrial myocardial damage, atherosclerotic
lesions of the extra- and intracranial arteries and aortic arch (these 3 causes are the most
common), as well as patent foramen ovale (PFO), heart defects, oncology, and concealed atrial
fibrillation. According to a 2015 observational study by LiL. et al. approximately one third
of all ischemic strokes are considered cryptogenic. An important contribution to the
development of cryptogenic stroke according to the data of a number of authors is made by an
unenlarged patent foramen ovale (PFO). Once the relationship between the development of
cryptogenic stroke and the PFO is established, the stroke is considered to be PFO-associated.
According to the literature, the incidence of a PFO in adult patients ranges from 20% to 35%.
The distinguishing feature of a PFO from an interatrial septal defect is impaired fusion of
the primary and secondary septum, rather than a deficiency.
There are various theories for the development of cryptogenic stroke in patients with a PFO.
The most popular is the presence and migration of thrombus from the inferior vena cava
system: predominantly the veins of the lower extremities, but also the pelvic veins. It is
also possible to develop thrombus in the PFO channel due to the change from laminar to
turbulent blood flow directly in the tunnel of the unclosed PFO. This mechanism of
cryptogenic stroke development is more theoretical and is not currently confirmed by the
literature.
In addition to the development of cryptogenic strokes in patients with a PFO there is a risk
of thromboembolism of other organs and systems. According to the literature, thrombus
migration through the PFO may be the cause of occlusion of arteries of the intestine, lower
and upper extremities. Clinical cases of thrombus migration through PFO have been described,
which led to occlusion of coronary arteries and development of acute myocardial infarction
with ST-segment elevation.
In the presence of cryptogenic stroke or other thromboembolism in patients with an unclosed
PFO, the contribution of the PFO to the development of vascular catastrophe is evaluated. The
Risk of Paradoxal Embolism (RoPE) scale was created. A high total score on the scale
indicates a high probability of a relationship between PFO and cryptogenic stroke. The scale
is a simple tool for clinicians, but in the European Society of Cardiology consensus document
on the treatment of patients with PFO, even a low score on this scale is not a
contraindication for endovascular treatment of patients with PFO.
Examination of patients with cryptogenic stroke or any other thromboembolism and the presence
of a PFO consists of transthoracic echocardiography (TTE), transcranial Dopplerography (TCD)
and transesophageal echocardiography (TSE). All studies are supplemented with the
administration of agitated saline solution (bubble test). Preparation of the agitated
solution consists of rapid mixing between two syringes of 1.0 mL of air and 10.0 mL of saline
solution. The mixing results in a solution with finely dispersed bubbles 40-80 microns in
size. The agitated solution is administered intravenously bolus, followed by a Valsalva test.
According to the study of Zhao E. et al. the most sensitive method of assessment of
right-to-left shunt is transcranial Doppler (TCD).
To date, a large evidence base has been accumulated for secondary prevention of cryptogenic
stroke in patients with PFO. In the large randomized international trials RESPECT, REDUCE,
CLOSE, and DEFENCE-PFO, the benefit of endovascular isolation of PFO compared with drug
therapy in patients with previous cryptogenic stroke has been shown.
In addition to RoPE risk assessment, the morphologic characteristics of a PFO, interatrial
septum, and the results of the bubble test should also be considered when selecting patients
for secondary prevention of cryptogenic stroke. Thus, in the study of S. Homma et al. showed
that the size of a PFO was significantly larger in patients with cryptogenic stroke compared
with patients with an identified cause of stroke (2.1 ± 1.7 mm versus 0.57 ± 0.78 mm; P <
0.01). In an observational study by Jong-Young Lee et al, the association of PFO with
cryptogenic stroke was exhibited in 184 patients out of 1014 patients with ischemic stroke
referred for transesophageal echocardiographic examination. During follow-up (median 3.5
years), 14 patients (7.7%) experienced stroke recurrence. Multivariate analysis demonstrated
that atrial septal aneurysm or atrial septal hypermobility (hazard ratio 6.04, 95% CI 1.84 to
19.86, p = 0.003) and PFO size (hazard ratio 3.00, 95% CI 1.96 to 4.60, p < 0.0001) were
independent predictors of recurrent stroke. The threshold value of PFO to predict recurrent
stroke within 3 years was 3.0 mm (95% confidence interval 2.1 to 3.7 mm, area under the curve
0.889, p < 0.001) with sensitivity and specificity of 90.0% and 79.4%, respectively. The
number of microbubbles in the bubble test was also greater in patients with cryptogenic
stroke compared with patients with an identifiable cause of stroke (13.9 ± 10.7 vs. 1.6 ± 0.8
[mean ± SD]; P < 0.0005).
The establishment of registries is an important part of the research armamentarium along with
interventional studies. A registry was established in the UK where data from patients with
cryptogenic stroke with indications for PFO closure were collected over a 2-year period.
Outcomes of interest included procedural success, health-related quality of life, and the
incidence of long-term death and neurologic complications. A total of 973 PFO closure
procedures in 971 patients were included in the analysis. Successful device implantation was
achieved in 99.4% [95% CI 98.6 to 99.8%] of procedures, with one patient dying in the
hospital. During a median follow-up period of 758 days (Q1:Q3 527:968), 33 patients had a
subsequent neurologic event, 76% of which were of ischemic origin. The incidence of
neurologic complications was 2.7% [95% CI 1.6 to 3.9%] at 1 year (n = 751) and 4.1% [95% CI
2.6 to 5.5%] at 2 years (n = 463) using Kaplan-Meier analysis. Improvements in patient
quality of life (utility and visual analog scale) were observed after 6 weeks and 6 months of
follow-up. In other studies, patient recruitment was more often from ischemic stroke
registries.
In Russia, studies on the efficacy and safety of endovascular PFO closure for the prevention
of cryptogenic stroke began to be conducted in 2018, but they are presented in sporadic
numbers and on a minimal sample of patients. To obtain data on procedural success rate,
incidence of distant adverse events, and efficacy of performed operations on the Russian
Federation patient population, conducting a registry study in accordance with the protocol,
GCP, and regulatory requirements with inclusion of all centers in the Russian Federation
performing endovascular PFO closure is maximally relevant.
Purpose of the study
The primary objectives of the study are:
1. To describe the baseline clinical and demographic characteristics of patients with PFO
who underwent its closure in Russia
2. To evaluate the efficacy and safety of endovascular closure of a PFO in Russia,
Secondary aim of the study:
1. To evaluate the procedural success rate of endovascular closure of PFO and the incidence
of adverse events;
2. To compare the technical features of implantation of different types of occluders in
endovascular closure of a PFO.
3. To establish the relationship between clinical characteristics of patients and long-term
prognosis of surgical treatment.
The study to evaluate the efficacy and safety of endovascular closure of a PFO in the Russian
Federation is planned on the basis of a telephone survey 1 year after the surgical
intervention.
Patient inclusion criteria
1. Patients with an ischemic event (cryptogenic ischemic stroke, transient ischemic attack,
embolism of other organs and systems) associated with a PFO;
2. Presence of an open oval confirmed by ultrasound diagnostic methods;
3. Age of patients from 18 years;
4. Life expectancy of at least 1 year;
5. Signed informed consent for endovascular closure of a PFO. Criteria for non-inclusion of
patients
1. Inability to receive antiplatelet therapy; 2. Presence of acute inflammatory diseases; 3.
Acute stage of cerebral circulatory failure (30 days); 4. Myocardial infarction or
aortocoronary bypass surgery within the previous 30 days; 5. Carotid or vertebral artery
dissection; 6. Severe cardiac valve pathology; 7. Presence of blood clots in the cardiac
cavities; 8. Refusal of the patient to participate in the study. Study design Patients
entering the study will have their attending physicians complete a "Patient Baseline Data"
card for the time of hospitalization. The card will be provided electronically to all
participating medical centers.
Data will be collected from patients in the study sample enrolled in the Registry by
telephone interview 12 months after the surgical intervention. The patient or his/her
relatives will be asked for the data necessary to fill in the registration card. The
registration card is available in paper and electronic version.
Therapeutic measures The operation of endovascular closure of PFO is performed on X-ray
angiographic devices with digital processing of X-ray images. Endovascular closure of a PFO
will be performed by femoral venous access using the following instruments: diagnostic
catheter, diagnostic guidewire, high-stiffness guidewire for delivery system, interatrial
septum occluders of PFO, UNI, ASD types.
Preoperative preparation and control of device implantation will be performed using modern
echocardiographic equipment.
Patients who are included in the Registry do not receive special surgical treatment.
Inclusion of the patient in the Registry does not affect the course of his surgery for
endovascular closure of a PFO.
Performance Evaluation
1. Immediate success of the operation.
2. Absence of complications after surgery.
3. Absence of recurrent stroke.
4. Absence of neurologic symptom development.
5. Absence of thromboembolic manifestations. The method of evaluation will be statistical
analysis of the collection of data reflected in the registration card, collected by
telephone interview.
Safety Assessment This study is safe for patients as it is a prospective observational
registry study. Patients who are enrolled in the Registry do not receive any specific
treatment or examination. Inclusion of a patient in the Registry does not affect the
patient's treatment. No treatment or diagnostic procedures are given to a patient because of
the patient's participation in the Registry. This Registry is a surveillance program.
