Clinical trial NCT06551727: Antithrombotic Therapy With Regulation of Blood Pressure in Non-Cardioembolic Progressive Stroke
Official title: Antithrombotic Therapy With Regulation of Blood Pressure in Non-Cardioembolic Progressive Stroke
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Stroke, Ischemic
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2024-08-13
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Stroke has become the leading cause of death in China, with acute ischemic stroke still progressing within one week of onset, known as progressive ischemic stroke (PIS), which has a high rate of disability and mortality, accounting for 23-43% of the incidence of stroke. Non-cardioembolic PIS is one of the common types, and the current treatment mainly focuses on antithrombotic therapy, but the therapeutic effect is not satisfactory. More and more evidence suggests that hypotension is an unfavorable factor for PIS, so this study intends to explore the efficacy and safety of antithrombotic therapy with regulation of blood pressure in non-cardioembolic PIS.

Detailed description: This is a single-center randomized controlled study conducted to explore the efficacy and safety of antithrombotic therapy with regulation of blood pressure in non-cardioembolic PIS.

We plan to recruit 70 patients with non-cardioembolic PIS. All subjects are of Han ethnicity, aged 18 years or older. Gender and age will be statistical data after enrollment. Patients will participate in the study after informed consent.

Then patients who meet the inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to the control group (antithrombotic therapy) or the intervention group (antithrombotic + blood pressure control therapy). In addition to antithrombotic therapy, the intervention group will use medications such as dopamine, metaraminol, or midodrine to control systolic blood pressure within the range of 160-180 mmHg and maintain it for one week.

Patients will be followed up at 2 weeks for mRS (Modified Rankin Scale) and NIHSS (National Institutes of Health Stroke Scale) scores，and at one month for mRS scores, and at three months for mRS and BI (Barthel Index) scores.

Eligibility criteria: Inclusion Criteria:

1. Adults (aged ≥18 years) with an AIS who have been able to complete usual activities in daily life without support before the stroke;
2. One of the following PIS manifestations:

   1. Within 7 days of onset, when symptom worsens and there are new lesions or infarct growth on DWI within 24 hours of aggravation, the National Institutes of Health Stroke Scale (NIHSS) score increases by ≥ 2 points ;
   2. Within 24 hours after IVT, when symptom worsens and there are new lesions or infarct growth on DWI within 24 hours of aggravation, the NIHSS score increases by ≥ 4 points compared to the baseline;
3. Within 3h of stroke progression, ≥2 successive measurements of systolic blood pressure (SBP) \< 160 mm Hg for \>10 min.
4. Computed tomographic angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography (DSA) confirms patients without visible large or medium-sized intracranial vessel occlusion.

Exclusion Criteria:

1. After stroke progression, a head CT confirmed new cerebral hemorrhage or hemorrhagic transformation.
2. Endovascualr treatment had been performed before stroke progression (thrombectomy, stent placement, balloon dilatation) or if surgery or interventional treatment had been scheduled;
3. Current treatment with heparin therapy or oral anticoagulation (presumed cardiac source of embolus, such as atrial fibrillation, prosthetic cardiac valve, and known or suspected endocarditis);
4. Previous diseases of the brain that include intracranial hemorrhage or amyloid angiopathy; brain surgery or hemorrhagic stroke; stroke within the last three months;
5. Preexisting serious diseases: Cancer, AIDS, serious heart disease, dementia, liver diseases such as liver failure, cirrhosis, portal hypertension and active hepatitis, acute or chronic severe renal impairment (glomerular filtration rate \< 30 ml/min/1·73 m2 );
6. Contraindication to aspirin or clopidogrel;
7. Pregnant and lactating women.

Primary outcomes:
measure: percentage of patients with an excellent outcome（mRS score 0-1）at 90 days after randomization
timeFrame: at 90 days after randomization
Secondary outcomes:
measure: proportion of patients with outcome measured by the Barthel index (BI)
timeFrame: at 90 days after randomization
measure: proportion of patients with outcome measured by mRS
timeFrame: at 90 days after randomization
measure: proportion of patients with an excellent outcome
timeFrame: at 2 weeks after randomization and at day 30 after randomization
measure: proportion of patients with functional independence
timeFrame: at 2 weeks after randomization and at day 30 after randomization
measure: proportion of patients with outcome measured by NIHSS
timeFrame: at 2 weeks after randomization
measure: proportion of patients with severe or moderate bleeding
timeFrame: at 90 days after randomization
measure: proportion of patients with any bleeding
timeFrame: at 90 days after randomization
measure: proportion of patients with death
timeFrame: at 90 days after randomization
measure: proportion of patients with adverse events
timeFrame: at 90 days after randomization
measure: proportion of patients with severe adverse events
timeFrame: at 90 days after randomization
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin North Hospital of Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
References:
citation: Helleberg BH, Ellekjaer H, Indredavik B. Outcomes after Early Neurological Deterioration and Transitory Deterioration in Acute Ischemic Stroke Patients. Cerebrovasc Dis. 2016;42(5-6):378-386. doi: 10.1159/000447130. Epub 2016 Jun 29.
citation: Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Effect of blood pressure and diabetes on stroke in progression. Lancet. 1994 Jul 16;344(8916):156-9. doi: 10.1016/s0140-6736(94)92757-x.
citation: Yang P, Song L, Zhang Y, Zhang X, Chen X, Li Y, Sun L, Wan Y, Billot L, Li Q, Ren X, Shen H, Zhang L, Li Z, Xing P, Zhang Y, Zhang P, Hua W, Shen F, Zhou Y, Tian B, Chen W, Han H, Zhang L, Xu C, Li T, Peng Y, Yue X, Chen S, Wen C, Wan S, Yin C, Wei M, Shu H, Nan G, Liu S, Liu W, Cai Y, Sui Y, Chen M, Zhou Y, Zuo Q, Dai D, Zhao R, Li Q, Huang Q, Xu Y, Deng B, Wu T, Lu J, Wang X, Parsons MW, Butcher K, Campbell B, Robinson TG, Goyal M, Dippel D, Roos Y, Majoie C, Wang L, Wang Y, Liu J, Anderson CS; ENCHANTED2/MT Investigators. Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial. Lancet. 2022 Nov 5;400(10363):1585-1596. doi: 10.1016/S0140-6736(22)01882-7. Epub 2022 Oct 28.