Clinical trial NCT05836753: Efficacy and Safety of Sarecycline in Patients With Acute Ischemic Stroke After Reperfusion Therapy
Official title: Efficacy and Safety of Sarecycline in Patients With Acute Ischemic Stroke After Reperfusion Therapy: A Phase II, Randomized, Multicenter, Double-blind, Single Dose, Placebo-controlled Parallel Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ischemic Stroke, Acute
Keywords: Ischemic Stroke, Sarecycline
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Neurodawn Pharmaceutical Co., Ltd.
First posted: 2023-05-01
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial was a prospective, randomized, multicenter, double-blind, placebo-controlled parallel trial. Subjects were randomly assigned according to the ratio of the experimental group: control group =2:1.
Primary purpose: TREATMENT

Brief summary: The aim of this study was to evaluate the efficacy and safety of Sarecycline versus placebo in the treatment of microcirculation dysfunction after reperfusion therapy in patients with large vessel occlusion stroke.

Detailed description: This study evaluated the efficacy and safety of 7-day Sarecycline versus placebo in patients with large vessel occlusion stroke who received reperfusion therapy within 24 hours of onset. In addition, we will explore the effect of Sarecycline versus placebo on indicators of venous thrombotic inflammation at different time points in patients with acute ischemic stroke with large vessel occlusion.

This trial was a prospective, randomized, multicenter, double-blind, placebo-controlled parallel trial. Patients with acute large vessel occlusion stroke who received reperfusion therapy within 24 hours of onset were randomly assigned according to the ratio of the experimental group: control group =2:1.

The trial was divided into three phases: screening/baseline period, treatment period, and follow-up period. The primary research objective is to evaluate the effect of Sarecycline in improving neurological deficits at 7 days in patients with acute large vessel occlusion stroke who received reperfusion therapy within 24 hours of onset.

Eligibility criteria: Inclusion criteria:

1. 18≤Age≤80 years old;
2. Acute large vessel occlusion (LVO) confirmed by imaging (CT+CTA+CTP/MRI+MRA), including the responsible vessel was located in the intracranial internal carotid artery, the T-shaped branch, the M1/M2 segment of the middle cerebral artery, or the A1/A2 segment of the anterior cerebral artery;
3. ASPECTS≥6;
4. 7≤NIHSS≤25,and Ia≤1;
5. Scheduled for reperfusion therapy within 24 hours of onset (including intravenous rt-PA or TNK-tPA thrombolysis (within 4.5 hours), mechanical thrombectomy, and bridging therapy);
6. First stroke or complete self-care before the onset of current stroke (mRS 0-1);
7. Patients or his/her legal representatives are able to understand and sign the informed consent.

Exclusion criteria:

1. History of pseudomembranous colitis or antibiotic-related colitis.
2. Allergic to tetracycline antibiotics or any component of the investigational drug.
3. Known to be resistant to other tetracyclines.
4. History of intracranial hemorrhagic diseases within the previous 3 months, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc.
5. Intracranial tumors, vascular malformations, and other intracranial space-occupying lesions.
6. Bilateral or posterior circulation LVO.
7. Rare or unknown etiology of LVO, such as dissection and vasculitis.
8. Severe hepatic or renal insufficiency and various reasons for receiving dialysis before randomization (Severe hepatic insufficiency was defined as ALT \>3 times the upper limit of normal value or AST \>3 times the upper limit of normal value; Severe renal insufficiency refers to serum creatinine \>3.0 mg/dl (265.2 μmol/L) or glomerular filtration rate\<30 ml/min).
9. Bleeding tendency (including but not limited to): platelet count \<100×109/L; Oral warfarin, INR \> 2; Received heparin within previous 48 hours, APTT≥35s; Hereditary hemorrhagic diseases, such as hemophilia.
10. Received any of the following treatments within the previous 3 months: systemic retinoic acid, androgen/antiandrogen therapy (e.g., anabolic steroids, andiolactone).
11. Refractory hypertension that is difficult to control with medication (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg).
12. History of intracranial or spinal surgery within the previous 3 months; History of therapeutical surgery or major physical trauma within the previous 1 month.
13. Have other investigator-evaluated contraindications of reperfusion therapy.
14. Women of childbearing age who do not use effective contraception and have no negative pregnancy test records; Women during lactation and pregnancy.
15. Life expectancy of fewer than 6 months due to advanced stage of any comorbidity.
16. Participated in other interventional clinical trials within the previous 3 months.
17. Other conditions that are not suitable for participating in this clinical trial, such as inability to understand and/or follow the research procedures due to mental, cognitive, emotional, or physical disorders, etc.

Primary outcomes:
measure: Changes of NIHSS score between baseline and at 7 days after randomization.
timeFrame: at 7 days after randomization
Secondary outcomes:
measure: Changes of NIHSS score between baseline and within 2 hours after reperfusion.
timeFrame: within 2 hours after reperfusion
measure: Changes of NIHSS score between baseline and 72 hours after randomization.
timeFrame: at 72 hours after randomization
measure: Early neurological deterioration at 72 hours after randomization.
timeFrame: at 72 hours after randomization.
measure: Early neurological deterioration at 7 days after randomization.
timeFrame: at 7 days after randomization
measure: Changes of infarction volume between baseline and at 72 hours after randomization.
timeFrame: at 72 hours after randomization
measure: Changes of cerebral blood perfusion between baseline and at 72 hours after randomization.
timeFrame: at 72 hours after randomization
measure: Changes of collateral circulation compensation between baseline and at 72 hours after randomization.
timeFrame: at 72 hours after randomization
measure: Modified Rankin Scale (mRS) score at 90 days after randomization.
timeFrame: at 90 days after randomization
measure: Quality of life (EQ-5D) score at 90 days after randomization.
timeFrame: at 90 days after randomization
measure: The proportion of combined vascular events (recurrent stroke, myocardial infarction, and vasogenic death) at 90 days after randomization.
timeFrame: at 90 days after randomization
Other outcomes:
measure: Venous thrombotic inflammation indicators compare with baseline.
timeFrame: within 2 hours after reperfusion therapy.
measure: Venous thrombotic inflammation indicators compare with baseline.
timeFrame: at 24±2 hours after randomization.
measure: Venous thrombotic inflammation indicators compare with baseline.
timeFrame: at 10±1 days after randomization
measure: Symptomatic intracranial hemorrhage.
timeFrame: at 24±2 hours after randomization
measure: Symptomatic intracranial hemorrhage.
timeFrame: at 10±1 day after randomization
measure: Any bleeding event.
timeFrame: at 90±7 days after randomization.
measure: Vascular death.
timeFrame: At 90±7 days after randomization.
measure: Overall mortality.
timeFrame: At 90±7 days after randomization.
measure: Investigator-reported adverse events/serious adverse events.
timeFrame: At 90±7 days of randomization.
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
Study officials:
affiliation: Beijing Tiantan Hospital, Capital Medical University, Beijing, , China
name: Yilong Wang, PhD，MD
role: PRINCIPAL_INVESTIGATOR
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