External Counterpulsation Therapy for Severe Steno-occlusive Intracranial Stenosis

Ischemic Stroke Clinical Trial

Official title:

External Counterpulsation Therapy for Symptomatic and Severe Steno-occlusive Disease of Intracranial Internal Carotid or Middle Cerebral Artery and Impaired Cerebral Vasodilatory Reserve

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03921827
• Other study ID #: NUSingapore_EECP
• Status: Recruiting
• Phase: N/A
• Start date: January 8, 2019
• Est. completion date: November 30, 2024

Study information

• Verified date: November 2023
• Source: National University of Singapore
• Contact: Lily YH Wong, RN
• Phone: +6567722517
• Email: lily_wong[@]nuhs.du.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Intracranial stenosis is prevalent among Asians and constitute a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in access of 10% per year, intracranial stenting was associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, being high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter-Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. The investigators hypothesize that EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA).

Description:

Among Asian patients, intracranial stenosis is more common and accounts for about 30-50% of all strokes. The risk of recurrent stroke or TIA in presence of intracranial stenosis of a major intracranial artery and recent TIA/ stroke is about 23% at 1 year despite treatment. Recurrence rate for stroke/TIA in intracranial atherosclerosis is dependent on degree of stenosis as well as presence of collaterals. In WASID study, patients with more than 70% stenosis had greater risk of recurrent event then those with 50-69%. Interestingly, patients with more than 70% intracranial stenosis with good collaterals demonstrated a lower risk for subsequent cerebral ischemic events. The two main mechanisms of ischemic stroke (IS) in these patients are thromboembolism and cerebral hemodynamic insufficiency. While Transcranial Doppler (TCD) monitoring can establish thrombo-embolic phenomenon and help in planning the appropriate antithrombotic treatment, assessment of dynamic cerebral hemodynamic insufficiency remains a complex issue, and may serve as a potential target for improving the outcomes (and reducing recurrent cerebral ischemia) in patients with severe intracranial stenoses. Treatment options for Intracranial stenosis: Anti-platelet agents are recommended for secondary prevention of IS. WASID trial compared warfarin with INR of 2-3 against aspirin, did not show any difference in outcome of stroke recurrence. Furthermore, aspirin was found to be safer as compared to warfarin. Use of short-term double antiplatelet therapy is shown to be effective in reducing stroke/TIA recurrence risk. In CLAIR study, patients with recent symptoms (70%) according to the velocity criteria and presence of 'blunted' flow spectra in the arterial segment distal to the stenosis. Therefore, tandem lesions in a single arterial tree (intracranial ICA and MCA, proximal MCA and distal MCA, extracranial ICA and ipsilateral intracranial ICA or extracranial ICA and ipsilateral MCA), if associated with blunted flow spectra in distal MCA would qualify the criteria for >70% stenosis. Importantly, the TCD diagnostic criteria for intracranial stenosis in our neurovascular laboratory have been validated against CT angiography. Patients would be randomized (1:1 by using drawing previously prepared chits in a bag) into either maximal medical management (plus sham EECP) or maximal medical management plus EECP. EECP sessions are planned 5 times/week for a total of 35 sessions. CVR would be measured at baseline as well as at 4 months of EECP treatment initiation. Improvement in CVR on symptomatic side would be measured by TCD-BHI as well as acetazolamide challenged HMPAO-SPECT and compared with patients in medical management (and sham EECP) arm for significant difference. Patients will also be followed up for recurrence of stroke/TIA during the study period. Maximal medical management would be same in both groups as per the current AHA/ASA guidelines. Briefly, all ischemic stroke cases with intracranial stenosis receive dual antiplatelet agents (aspirin and clopidogrel for 1 month followed by clopidogrel or aspirin long term). The investigators aim to keep HbA1c at 7% or less in all cases. Blood pressure target in the stroke patients eligible for this study (at least 1 month after acute stroke) is less than 140/90mmHg. For lipids, the target LDL is less than 2.6mmol/L.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: November 30, 2024
• Est. primary completion date: March 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. Patients with recent stroke/TIA and severe stenosis of intracranial ICA or MCA and impaired CVR within previous three months but not before 3 weeks after acute stroke. This is to differentiate between patients with a long-standing fixed-stenosis from patients with partially recanalized intracranial artery (masquerading as severe stenosis).

2. Age >21 years

Exclusion Criteria:

1. Patients with atrial fibrillation/ arrhythmias.

2. Within 2 weeks of cardiac catheterization or arterial puncture at femoral puncture site.

3. Decompensated heart failure , usually class 3 or 4

4. LV EF <30%

5. Moderate or severe AR

6. Persistent and uncontrolled hypertension (BP persistently >160/100 mmHg)

7. Bleeding diathesis

8. Active thrombophlebitis/ venous disease of lower limbs

9. Severe lower extremity vaso-occlusive disease

10. Presence of a documented aortic aneurysm/ dissection requiring surgical repair

11. Pregnancy

Related Conditions & MeSH terms

• Ischemic Stroke

Intervention

Device:
• Enhance External Counterpulsation Therapy
EECP therapy would be administered to this group for 1-hour a day for a total of 35 sessions

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
National University of Singapore	National University Health System, Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in cerebral vasodilatory reserve	To evaluate whether Enhanced External Counter-Pulsation (EECP) therapy would lead to a change in cerebral vasodilatory reserve (CVR) by at least 4% in patients with severe and recently symptomatic stenosis of intracranial carotid (ICA) or middle cerebral artery (MCA).	at baseline and after 2 months of the completion of EECP therapy
Secondary	Stroke TIA/recurrence	To evaluate the impact of EECP on recurrence of cerebral ischemic event in patients with severe and recently symptomatic stenosis of ICA or MCA.	at 6 months
Secondary	Impact of EECP on cognition	To evaluate the impact of EECP on change in neurocognitive performance by at least 2 points (60 minutes protocol suggested by NINDS harmonization workshop) in patients with severe and recently symptomatic stenosis of ICA or MCA.	at 6 months