Testing Recombinant human tissue kallikrein against a placebo for acute stroke

Exclusion

• −Participant had a pre-morbid mRS score of 0 to 1 (mRS score prior to AIS) as stated by participant or participant's representative.
• −Participant has large core of established infarction defined as ASPECTS 0-5.
• −Participant has a history of clinically significant allergic reactions such as angioedema or anaphylaxis requiring hospitalization.
• −, including repeat brain imaging to rule out hemorrhagic transformation.
• −If participant has received fibrinolytic treatment for AIS within 4.5 hours of last know normal/AIS stoke onset and at least 6 hours after completing fibrinolytic treatment, and the participant meets all of the following criteria:
• −Participant's initial NIHSS score prior to fibrinolytics was ≤15; and
• −At least six hours after fibrinolytics, the participant has NIHSS score of ≥5 and ≤15 with a persistent deficit; and
• −The participant's NIHSS score showed less than a 4-point improvement, or worsened, after receiving fibrinolytics; and
• −Participant meets all other inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → and exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → including repeat brain imaging to rule out hemorrhagic transformation.
• −Participant and/or legally authorized representative is able to provide informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →.
• −Participant is willing and able to comply with the study protocolProtocolThe detailed plan a study must follow.Read more →, in the InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →'s judgment.
• −Exclusion Criteria:
• −At screeningScreeningThe checks done before joining, to see whether a study fits.Read more →, or with repeat imaging (see Inclusion 4 and 6), participant has imaging confirmed hemorrhage stroke.
• −Participant has image findings with symptomatic large vessel occlusion at one or more of the following locations: Intracranial carotid I/T/L or M1 segment MCA, vertebral or basilar artery (BA).
• −Participant has or will receive MT for their current AIS.
• −Participant has suspected or confirmed extracranial arterial dissection.
• −Participant has imaging findings and/or symptoms consistent with a brain stem or cerebellar stroke. Posterior cerebral artery strokes without any associated brain stem or cerebellar involvement are allowable.
• −Participant has any recorded SBP \<100 mmHg or MAP \<65 mmHg; MAP = DBP + \[1/3 (SBP - DBP)\] (measured with noninvasive BP cuff type monitor) after stroke symptom onset and prior to randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →.
• −Participant is currently prescribed angiotensin-converting enzyme inhibitor (ACEi) and is unable or unwilling to convert to another antihypertensive pharmacological treatment through Day 29 ±1 day (8 days after last treatment).
• −Participant is currently prescribed an ACEi, and the last dose of the ACE inhibitor medication is reported to have been taken \< 24 hours before start of IV study drug infusion as stated by participant or participant's representative.
• −Participant has a diagnosis or suspected diagnosis of hereditary angioedema (HAE) or is taking or prescribed medications commonly used as prophylaxis/treatment of HAE, such as C1-esterase inhibitors (Cinryze, Berinert, Ruconest, Haegarda), Danazol, kallikrein inhibitors (Ecallantide, Berotralstat, Lanadelumab), Bradykinin B2 Receptor Antagonists (Icatibant), or other medication designed to influence the kallikrein-kinin system.
• −Life expectancy estimated at ≤1 year prior to enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →.
• −Participant has clinical evidence of an active infection at the time of enrollment requiring parenteral treatment or hospitalization to monitor or manage the infection.
• −NOTE: Treatment of uncomplicated infections with oral antibiotics would not be an exclusion (for example, the treatment of uncomplicated urinary tract infections or sinus infections with oral antibiotics would not be exclusionary).
• −Participant has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency).
• −Participants participating in sexual activity must agree to use, or for their partner to use highly effective birth controlControl groupThe group a new treatment is measured against.Read more → methods (those with a failure rate of less than 1% per year when used consistently and correctly) until they have completed the study (after the Day 90 visit). Such methods include:
• −Intrauterine device (IUD)
• −Intrauterine hormone-releasing system (IUS)
• −Bilateral tubal occlusion
• −Vasectomized partner
• −Participant is currently participating in or has participated in a study using an investigational device or drug or received an investigational drug or investigational use of a licensed drug within 30 days prior to screening.
• −Participant does not have sufficient venous access for infusion of study treatment or blood sampling.
• −Participant is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-upFollow-upContinued check-ins after the treatment part is finished.Read more → visits.
• −Participant has any other medical condition which in the opinion of the Investigator will make participation medically unsafe or interfere with the study results.
• −Participant is pregnant or nursing. NOTE: Participants who agree to stop nursing may be considered for inclusion at the discretion of the Investigator.
• −Participants of child-bearing potential must agree to use medically acceptable contraceptive measures to prevent pregnancy. All participants of childbearing potential (defined as sexually mature participants who have had menses within the preceding 24 months and have not undergone permanent sterilization methods such as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, etc.) must have a negative serum pregnancy test performed locally at screening. Participants of childbearing potential must agree not to attempt to become pregnant or undergo in vitro fertilization. If participating in sexual activity that could lead to pregnancy, participants must use 2 reliable methods (1 per partner is acceptable) of contraception simultaneously while receiving protocol-specified medication and during the study follow-up period.
• −Combined (estrogen and progesterone containing) hormonal oral, intravaginal, or transdermal contraception associated with the inhibition of ovulation
• −Progesterone-only oral, injectable, or implantable hormonal contraception associated with the inhibition of ovulation
• −Sexual abstinence Participants who are not of reproductive potential (who have been postmenopausal for more than 24 consecutive months or have undergone hysterectomy, bilateral oophorectomy, bilateral salpingectomy, etc.) are not required to use contraception.
• −Participants are prohibited from sperm donation. NOTE: A negative serum pregnancy test will be documented during screening if a participant is of child-bearing potential.