Ignite Creation Date:
2024-05-06 @ 8:14 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06308952
Status:
RECRUITING
Last Update Posted:
2024-06-05
First Post:
2024-03-05
Brief Title:
Effectiveness of Atorvastatin in Preventing Cerebrovascular Events After Flow Diverter Implantation
Sponsor:
Zhujiang Hospital
Organization:
Zhujiang Hospital
Study Overview
Official Title:
To Evaluate the Efficacy of Atorvastatin in the Prevention of Cerebrovascular Events After Flow Diverter Implantation in Patients With Unruptured Intracranial Aneurysms
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
With the development of medical technology and materials and instruments flow diverter FD has gradually become the most important treatment method for the treatment of intracranial aneurysms IA At present FD has been used in more than 250000 cases worldwide and the overall 1-year complete occlusion rate of aneurysms can reach 75-855 However although the current imaging prognosis of FD is encouraging the perioperative complications of FD are as high as 129 including ischemic complications SAH and parenchymal hemorrhage in 73 20 and 20 respectively In addition an in-stent stenosis of more than 50 within one year has been reported in 102 to 150 of patients However in addition to conventional dual antiplatelet therapy there is no relevant guideline recommendation or clinical evidence on how to prevent complications after FD implantation in IA patients Atorvastatin is widely used in the primary and secondary prevention of cardiovascular and cerebrovascular diseases Its main effect is to improve the incidence of cardiovascular and cerebrovascular events by reducing blood lipids However there is no high-quality clinical evidence for the use of atorvastatin in intracranial aneurysm stent implantation Previous retrospective studies have shown that atorvastatin is the only protective factor for in-stent restenosis after flow diverter implantation in intracranial aneurysms Therefore this study planned to conduct a randomized controlled clinical trial to confirm the efficacy and safety of oral atorvastatin in the prevention of cerebrovascular adverse events after stent implantation in patients with unruptured intracranial aneurysms and to provide objective evidence for the treatment decision of patients with unruptured intracranial aneurysms to prevent cerebrovascular adverse events after flow diverter implantation
Detailed Description:
1 Objectives of the study 11 Primary objective To evaluate the efficacy of oral atorvastatin in preventing adverse cerebrovascular events within 1 year after flow diverter implantation in patients with intracranial aneurysms
12 Secondary Objectives
1 To evaluate the effectiveness of atorvastatin treatment in the prevention of adverse cerebrovascular events at 30 days and 180 days
2 To evaluate the safety of atorvastatin treatment in patients with unruptured IA within 1 year after flow diverter implantation
3 To evaluate the efficacy of atorvastatin in the prevention of in-stent stenosis events at 1 year after flow diverter implantation and to explore its intervention effect on the degree of in-stent stenosis
And 4 to evaluate whether there is a difference in the embolization rate of treated aneurysms between atorvastatin treatment and placebo at 1 year after flow diverter implantation
2 Research hypothesis Atorvastatin treatment can effectively prevent cerebrovascular adverse events in patients with unruptured intracranial aneurysms treated with flow diverter implantation
3 Study design This study was a multicenter randomized double-blind placebo-controlled superiority clinical trial to evaluate the efficacy and safety of oral atorvastatin in the prevention of postoperative cerebrovascular events in patients with unruptured intracranial aneurysms treated with flow diverters Subjects press 1 Patients were followed up at postoperative day discharge day 303 days 1807 days and 121 month Neurological examination and mRS Scores were evaluated by observers at each follow-up period According to the clinical symptoms and scores of the subjects the observer decided whether to conduct further CTCTA MRMRA and DSA to confirm whether there were cerebrovascular events
4 Study subjects Patients 18 to 75 years of age who had a diagnosed unruptured intracranial aneurysm and were intended to be treated with a flow diverter met all the inclusion criteria and none of the exclusion criteria According to the PLUS study the incidence of cerebrovascular events after the treatment of intracranial aneurysms with flow diverter device was 358 which was used as the reference level Combined with the retrospective analysis of our center the incidence of cerebrovascular events was expected to be less than 13 which was better than 10 of the control group When the power was 80 the sample size estimation formula for superiority design of qualitative variables was used and the dropout rate was estimated to be 15 193 patients were required to be recruited in each group and a total of 386 patients were enrolled in the two groups 41 Diagnostic Criteria Unruptured intracranial aneurysms were confirmed by CTA or MRA or DSA 42 Inclusion Criteria
1 male or non-pregnant women aged 18-75 years
2 Unruptured IA confirmed by CTA MRA or DSA
3 IA size ranged from 3 mm to 25mm
4 Patients andor their authorized persons can understand the purpose of the study voluntarily participate in and sign informed consent
5 patients who could be treated with flow diverter implantation according to the evaluation of the investigator
6 patients who were willing to be followed up and evaluated according to the clinical research protocol
43 Exclusion Criteria
1 Patients with contraindications to atorvastatin treatment or patients with oral allergy to atorvastatin
2 female patients in preparation for pregnancy pregnancy or lactation
3 patients with other cardiovascular and cerebrovascular diseases except intracranial aneurysms
4 patients with long-term oral atorvastatin therapy before surgery continuous use of atorvastatin for more than 1 month
5 patients with ruptured IA or patients with previous surgical treatment for IA
6 taking transport protein inhibitors cyclosporine protease inhibitors other lipid-lowering products fibrates ezetimibe evolocumab antacids erythromycin cytochrome P450 enzymes colchicine and other concomitant drugs that interact with atorvastatin metabolism
7 patients with multiple intracranial aneurysms requiring treatment of 2 intracranial aneurysms within 1 year
8 patients with blood blister-like aneurysm fusiform aneurysm dissecting aneurysm pseudoaneurysm infectious aneurysm arteriovenous malformation related aneurysm moyamoya disease related aneurysm
9 known severe allergy to contrast media or to anticoagulant antiplatelet drugs anesthetic drugs Nitinol alloy Patients with established allergies or contraindications
10 patients who were not suitable for intravenous anesthesia or tracheal intubation general anesthesia according to the evaluation of anesthesiologists
11 patients who did not understand or were unwilling to undergo follow-up evaluation as required by the clinical research protocol
12 life expectancy 3 years
13 patients who were participating in clinical trials of other drugs or medical devices
5Blind method The trial drug atorvastatin calcium tablets 20mg was white oval film coated tablets tasteless In the control group starch mimic tablet 20mg was used as a white oval film coated tablet The outer packaging of the drug was aluminum blister eye packaging
In order to ensure the blinding of the investigators and subjects during the execution of the trial the unblinded personnel responsible for the administration and configuration of the trial drug will sign a confidentiality agreement The investigators other blinded investigators subjects and the sponsor will not have access to any information about the group assignment and related documents of the trial drug
6Endpoints
Primary outcome measures
61Efficacy endpoint no new cerebrovascular adverse events within 1 year
Including new cases caused by various reasons
① hemorrhagic stroke New cerebral hemorrhage confirmed by head CT
② ischemic stroke Neurological impairment more than 24 hours after onset or new acute cerebral infarction lesion confirmed by imaging
③ Angiographic follow-up at 121 month degree of in-stent stenosis 50 measured by WASID method
Secondary end points
62 Safety endpoint no new moderate or serious adverse events within 1 year
Meet one of the following conditions
① Muscle-related adverse events sports trauma and other injuries were excluded ② new-onset diabetes ③ Dyspepsia or abdominal pain unexplained for other reasons ④ gallbladder-related adverse events ⑤ Heavy bleeding ⑥ all other patients who met the definition of moderate or serious adverse events ⑦ Diagnosis of new cancers 8 new-onset neurocognitive disorders ⑨ Cataract
1 All-cause mortality events within 1 year
2 Incident ischemic stroke events within 1 year
3 New hemorrhagic stroke events within 1 year
4 New stent thrombosis events within 1 year
5 New symptomatic stenosis events within 1 year
6 In-stent stenosis stenosis 50 by WASID method occurred at the 12th 1 month of angiographic follow-up
7 Degree of in-stent stenosis as measured by WASID method at the 12th 1 month annual angiographic follow-up Target aneurysm embolization rate at 121 month annual angiographic follow-up Raymond and OKM classification
12 Secondary Objectives
1 To evaluate the effectiveness of atorvastatin treatment in the prevention of adverse cerebrovascular events at 30 days and 180 days
2 To evaluate the safety of atorvastatin treatment in patients with unruptured IA within 1 year after flow diverter implantation
3 To evaluate the efficacy of atorvastatin in the prevention of in-stent stenosis events at 1 year after flow diverter implantation and to explore its intervention effect on the degree of in-stent stenosis
And 4 to evaluate whether there is a difference in the embolization rate of treated aneurysms between atorvastatin treatment and placebo at 1 year after flow diverter implantation
2 Research hypothesis Atorvastatin treatment can effectively prevent cerebrovascular adverse events in patients with unruptured intracranial aneurysms treated with flow diverter implantation
3 Study design This study was a multicenter randomized double-blind placebo-controlled superiority clinical trial to evaluate the efficacy and safety of oral atorvastatin in the prevention of postoperative cerebrovascular events in patients with unruptured intracranial aneurysms treated with flow diverters Subjects press 1 Patients were followed up at postoperative day discharge day 303 days 1807 days and 121 month Neurological examination and mRS Scores were evaluated by observers at each follow-up period According to the clinical symptoms and scores of the subjects the observer decided whether to conduct further CTCTA MRMRA and DSA to confirm whether there were cerebrovascular events
4 Study subjects Patients 18 to 75 years of age who had a diagnosed unruptured intracranial aneurysm and were intended to be treated with a flow diverter met all the inclusion criteria and none of the exclusion criteria According to the PLUS study the incidence of cerebrovascular events after the treatment of intracranial aneurysms with flow diverter device was 358 which was used as the reference level Combined with the retrospective analysis of our center the incidence of cerebrovascular events was expected to be less than 13 which was better than 10 of the control group When the power was 80 the sample size estimation formula for superiority design of qualitative variables was used and the dropout rate was estimated to be 15 193 patients were required to be recruited in each group and a total of 386 patients were enrolled in the two groups 41 Diagnostic Criteria Unruptured intracranial aneurysms were confirmed by CTA or MRA or DSA 42 Inclusion Criteria
1 male or non-pregnant women aged 18-75 years
2 Unruptured IA confirmed by CTA MRA or DSA
3 IA size ranged from 3 mm to 25mm
4 Patients andor their authorized persons can understand the purpose of the study voluntarily participate in and sign informed consent
5 patients who could be treated with flow diverter implantation according to the evaluation of the investigator
6 patients who were willing to be followed up and evaluated according to the clinical research protocol
43 Exclusion Criteria
1 Patients with contraindications to atorvastatin treatment or patients with oral allergy to atorvastatin
2 female patients in preparation for pregnancy pregnancy or lactation
3 patients with other cardiovascular and cerebrovascular diseases except intracranial aneurysms
4 patients with long-term oral atorvastatin therapy before surgery continuous use of atorvastatin for more than 1 month
5 patients with ruptured IA or patients with previous surgical treatment for IA
6 taking transport protein inhibitors cyclosporine protease inhibitors other lipid-lowering products fibrates ezetimibe evolocumab antacids erythromycin cytochrome P450 enzymes colchicine and other concomitant drugs that interact with atorvastatin metabolism
7 patients with multiple intracranial aneurysms requiring treatment of 2 intracranial aneurysms within 1 year
8 patients with blood blister-like aneurysm fusiform aneurysm dissecting aneurysm pseudoaneurysm infectious aneurysm arteriovenous malformation related aneurysm moyamoya disease related aneurysm
9 known severe allergy to contrast media or to anticoagulant antiplatelet drugs anesthetic drugs Nitinol alloy Patients with established allergies or contraindications
10 patients who were not suitable for intravenous anesthesia or tracheal intubation general anesthesia according to the evaluation of anesthesiologists
11 patients who did not understand or were unwilling to undergo follow-up evaluation as required by the clinical research protocol
12 life expectancy 3 years
13 patients who were participating in clinical trials of other drugs or medical devices
5Blind method The trial drug atorvastatin calcium tablets 20mg was white oval film coated tablets tasteless In the control group starch mimic tablet 20mg was used as a white oval film coated tablet The outer packaging of the drug was aluminum blister eye packaging
In order to ensure the blinding of the investigators and subjects during the execution of the trial the unblinded personnel responsible for the administration and configuration of the trial drug will sign a confidentiality agreement The investigators other blinded investigators subjects and the sponsor will not have access to any information about the group assignment and related documents of the trial drug
6Endpoints
Primary outcome measures
61Efficacy endpoint no new cerebrovascular adverse events within 1 year
Including new cases caused by various reasons
① hemorrhagic stroke New cerebral hemorrhage confirmed by head CT
② ischemic stroke Neurological impairment more than 24 hours after onset or new acute cerebral infarction lesion confirmed by imaging
③ Angiographic follow-up at 121 month degree of in-stent stenosis 50 measured by WASID method
Secondary end points
62 Safety endpoint no new moderate or serious adverse events within 1 year
Meet one of the following conditions
① Muscle-related adverse events sports trauma and other injuries were excluded ② new-onset diabetes ③ Dyspepsia or abdominal pain unexplained for other reasons ④ gallbladder-related adverse events ⑤ Heavy bleeding ⑥ all other patients who met the definition of moderate or serious adverse events ⑦ Diagnosis of new cancers 8 new-onset neurocognitive disorders ⑨ Cataract
1 All-cause mortality events within 1 year
2 Incident ischemic stroke events within 1 year
3 New hemorrhagic stroke events within 1 year
4 New stent thrombosis events within 1 year
5 New symptomatic stenosis events within 1 year
6 In-stent stenosis stenosis 50 by WASID method occurred at the 12th 1 month of angiographic follow-up
7 Degree of in-stent stenosis as measured by WASID method at the 12th 1 month annual angiographic follow-up Target aneurysm embolization rate at 121 month annual angiographic follow-up Raymond and OKM classification
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None