Efficacy and Safety of Sarecycline in Patients With Acute Ischemic Stroke After Reperfusion Therapy

NCT05836753 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: KY2023-026-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke, Acute

Keywords

Ischemic Stroke, Sarecycline

Outcome Measures

Primary Outcomes (1)

• Changes of NIHSS score between baseline and at 7 days after randomization.

  National Institute of Health stroke scale (NIHSS 0-42 scores; higher scores mean a worse outcome）

  at 7 days after randomization

Secondary Outcomes (10)

• Changes of NIHSS score between baseline and within 2 hours after reperfusion.

  within 2 hours after reperfusion

• Changes of NIHSS score between baseline and 72 hours after randomization.

  at 72 hours after randomization

• Early neurological deterioration at 72 hours after randomization.

  at 72 hours after randomization.

• Early neurological deterioration at 7 days after randomization.

  at 7 days after randomization

• Changes of infarction volume between baseline and at 72 hours after randomization.

  at 72 hours after randomization

Other Outcomes (9)

• Venous thrombotic inflammation indicators compare with baseline.

  within 2 hours after reperfusion therapy.

• Venous thrombotic inflammation indicators compare with baseline.

  at 24±2 hours after randomization.

• Venous thrombotic inflammation indicators compare with baseline.

  at 10±1 days after randomization

Study Arms (2)

Sarecycline treatment group

ACTIVE COMPARATOR

The first dose should be given immediately after randomization (within 30 minutes); Take one tablet once a day for 7 days continuously (the patient with dysphagia will be administrated through a nasal feeding tube).

Drug: Sarecycline Tablet

Sarecycline placebo control group

PLACEBO COMPARATOR

The control group received Sarecycline placebo tablets (each containing Sarecycline 0 mg) in the same way as the experimental group.

Drug: Placebo tablets of Sarecycline tablets

Interventions

Sarecycline Tablet DRUG

Each tablet contained 100 mg of Sarecycline.

Sarecycline treatment group

Placebo tablets of Sarecycline tablets DRUG

Each tablet contained 0 mg of Sarecycline.

Sarecycline placebo control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≤Age≤80 years old;
• 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;
• ASPECTS≥6;
• ≤NIHSS≤25,and Ia≤1;
• 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);
• First stroke or complete self-care before the onset of current stroke (mRS 0-1);
• Patients or his/her legal representatives are able to understand and sign the informed consent.

You may not qualify if:

• History of pseudomembranous colitis or antibiotic-related colitis.
• Allergic to tetracycline antibiotics or any component of the investigational drug.
• Known to be resistant to other tetracyclines.
• History of intracranial hemorrhagic diseases within the previous 3 months, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc.
• Intracranial tumors, vascular malformations, and other intracranial space-occupying lesions.
• Bilateral or posterior circulation LVO.
• Rare or unknown etiology of LVO, such as dissection and vasculitis.
• 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).
• 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.
• Received any of the following treatments within the previous 3 months: systemic retinoic acid, androgen/antiandrogen therapy (e.g., anabolic steroids, andiolactone).
• Refractory hypertension that is difficult to control with medication (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg).
• History of intracranial or spinal surgery within the previous 3 months; History of therapeutical surgery or major physical trauma within the previous 1 month.
• Have other investigator-evaluated contraindications of reperfusion therapy.
• Women of childbearing age who do not use effective contraception and have no negative pregnancy test records; Women during lactation and pregnancy.
• Life expectancy of fewer than 6 months due to advanced stage of any comorbidity.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Neurodawn Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Beijing Tiantan Hospital

Beijing, 100050, China

RECRUITING

Related Publications (13)

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  PMID: 19834014 RESULT

• Hussein HM, Georgiadis AL, Vazquez G, Miley JT, Memon MZ, Mohammad YM, Christoforidis GA, Tariq N, Qureshi AI. Occurrence and predictors of futile recanalization following endovascular treatment among patients with acute ischemic stroke: a multicenter study. AJNR Am J Neuroradiol. 2010 Mar;31(3):454-8. doi: 10.3174/ajnr.A2006. Epub 2010 Jan 14.

  PMID: 20075087 RESULT

• Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18.

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• van Horn N, Kniep H, Leischner H, McDonough R, Deb-Chatterji M, Broocks G, Thomalla G, Brekenfeld C, Fiehler J, Hanning U, Flottmann F. Predictors of poor clinical outcome despite complete reperfusion in acute ischemic stroke patients. J Neurointerv Surg. 2021 Jan;13(1):14-18. doi: 10.1136/neurintsurg-2020-015889. Epub 2020 May 15.

  PMID: 32414889 RESULT

• Casetta I, Fainardi E, Saia V, Pracucci G, Padroni M, Renieri L, Nencini P, Inzitari D, Morosetti D, Sallustio F, Vallone S, Bigliardi G, Zini A, Longo M, Francalanza I, Bracco S, Vallone IM, Tassi R, Bergui M, Naldi A, Saletti A, De Vito A, Gasparotti R, Magoni M, Castellan L, Serrati C, Menozzi R, Scoditti U, Causin F, Pieroni A, Puglielli E, Casalena A, Sanna A, Ruggiero M, Cordici F, Di Maggio L, Duc E, Cosottini M, Giannini N, Sanfilippo G, Zappoli F, Cavallini A, Cavasin N, Critelli A, Ciceri E, Plebani M, Cappellari M, Chiumarulo L, Petruzzellis M, Terrana A, Cariddi LP, Burdi N, Tinelli A, Auteri W, Silvagni U, Biraschi F, Nicolini E, Padolecchia R, Tassinari T, Filauri P, Sacco S, Pavia M, Invernizzi P, Nuzzi NP, Marcheselli S, Amista P, Russo M, Gallesio I, Craparo G, Mannino M, Mangiafico S, Toni D; Italian Registry of Endovascular Treatment in Acute Stroke. Endovascular Thrombectomy for Acute Ischemic Stroke Beyond 6 Hours From Onset: A Real-World Experience. Stroke. 2020 Jul;51(7):2051-2057. doi: 10.1161/STROKEAHA.119.027974. Epub 2020 Jun 17.

  PMID: 32568647 RESULT

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• GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1545-1602. doi: 10.1016/S0140-6736(16)31678-6.

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• El Amki M, Wegener S. Improving Cerebral Blood Flow after Arterial Recanalization: A Novel Therapeutic Strategy in Stroke. Int J Mol Sci. 2017 Dec 9;18(12):2669. doi: 10.3390/ijms18122669.

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• Bustamante A, Ning M, Garcia-Berrocoso T, Penalba A, Boada C, Simats A, Pagola J, Ribo M, Molina C, Lo E, Montaner J. Usefulness of ADAMTS13 to predict response to recanalization therapies in acute ischemic stroke. Neurology. 2018 Mar 20;90(12):e995-e1004. doi: 10.1212/WNL.0000000000005162. Epub 2018 Feb 14.

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  PMID: 31296369 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

sarecycline

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Yilong Wang, PhD，MD

  Beijing Tiantan Hospital, Capital Medical University, Beijing, , China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yilong Wang, PhD，MD

CONTACT

0086-010-67092222; yilong528@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Sarecycline drug used in the study is indistinguishable from the Sarecycline placebo (the shape, color, and appearance are identical). In addition, to ensure the blind method, the drug packaging and batch numbers of the two groups are identical, and the packaging batch numbers are uniformly marked. During the implementation of the study, except for the authorized personnel of the company's supply chain, research management department, and subject security department, members of each research execution group, research center personnel, and CRO data processing personnel cannot view the randomization scheme. The blind method was also used to evaluate the outcome. The subjects were randomly divided into groups and blinded to the members of the adjudication committee.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Model Details: 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.

Study Record Dates

• First Submitted: April 19, 2023
• First Posted: May 1, 2023
• Study Start: May 7, 2023
• Primary Completion: November 1, 2023
• Study Completion: December 1, 2023
• Last Updated: July 20, 2023

Record last verified: 2023-07

Locations

CN (1)