Search Results Within Category "Neurology"
10results
Computerized Registry of Patients With Venous Thromboembolism (RIETE) (RIETE)
clinicaltrials@northshore.org
ALL
Not specified
NCT02832245
Inclusion Criteria:
* Confirmed VTE (acute deep-vein thrombosis, pulmonary embolism and/or superficial venous thrombosis) by objective tests.
* Informed consent to the participation in the study, according to the requirements of the ethics committee within each hospital.
Exclusion Criteria:
* Participation in a therapeutic clinical trial with an unknown drug.
* Inability to the 3 month follow-up Venous Thromboembolism
Stroke Thrombectomy and Aneurysm Registry (STAR)
clinicaltrials@northshore.org
ALL
1 year to 120 years old
NCT04994756
Inclusion Criteria:
* Undergoing surgical intervention for central nervous system vascular lesion
* Between 1 and 120 years of age
Exclusion Criteria:
* No exclusion criteria PROCEDURE: Stroke/Thrombectomy/Aneurysm-specific surgical procedures
Stroke, Thromboses, Intracranial, Aneurysm, Brain
Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (ReMEDy2)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE2
NCT05065216
Inclusion Criteria:
• Participant is ≥18 years of age.
• Participant weight is 50 kg to 160 kg inclusive.
• Participant to be randomized and treatment initiated within 24 hours of last known normal/AIS stroke onset.
• Participant has NIHSS ≥5 and ≤ 15 at approximately the time of randomization.
• 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 and/or legally authorized representative is able to provide informed consent.
• Participant is willing and able to comply with the study protocol, in the Investigator's judgment.
Exclusion Criteria:
• Participant has any evidence of intracranial hemorrhage.
• Participant has received or will receive fibrinolytics for their current AIS.
• Participant has image findings with symptomatic large vessel occlusion at one or more of the following locations: Intracranial carotid I/T/L, M1 or M2 segment MCA, vertebral or basilar artery (BA).
• Participant has large core of established infarction defined as ASPECTS 0-4.
• Participant has or will receive MT for their current AIS.
• Participant has imaging findings and/or symptoms consistent with a posterior circulation stroke.
• Participant has any recorded SBP \< 100 mm HG or MAP \<65 mm Hg; MAP = DBP + \[1/3 (SBP - DBP)\] (measured with noninvasive BP cuff type monitor) after stroke symptom onset and prior to randomization.
• 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).
• If 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 history of clinically significant allergic reactions such as angioedema or anaphylaxis requiring hospitalization.
• Life expectancy estimated at ≤ 1 year prior to enrollment.
• 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 (example treatment of an uncomplicated urinary tract infections or sinus infections with oral antibiotics would not be an exclusion).
• Participant has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency).
• 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. Participants participating in sexual activity must agree to use, or for their partner to use highly effective birth control 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: * 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 * Intrauterine device (IUD) * Intrauterine hormone-releasing system (IUS) * Bilateral tubal occlusion * Vasectomized partner * 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) 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.
• 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-up 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.
DRUG: Recombinant human tissue kallikrein
Acute Stroke, Ischemic Stroke, Stroke
acute, ischemic, stroke, AIS, tPA, LVO, MT, KLK1, Kallikreins
A Study Comparing Abelacimab to Apixaban in the Treatment of Cancer-associated VTE (ASTER)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT05171049
Inclusion Criteria:
* Male or female subjects ≥18 years old or other legal maturity age according to the country of residence
* Confirmed diagnosis of cancer (by histology, adequate imaging modality), other than basal-cell or squamous-cell carcinoma of the skin alone with one of the following:
* Active cancer, defined as either locally active, regionally invasive, or metastatic cancer at the time of randomization and/or
* Currently receiving or having received anticancer therapy (radiotherapy, chemotherapy, hormonal therapy, any kind of targeted therapy or any other anticancer therapy) in the last 6 months.
* Confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT) (i.e., popliteal, femoral, iliac, and/or inferior vena cava \[IVC\] thrombosis) and/or a confirmed symptomatic pulmonary embolism (PE), or an incidental PE in a segmental, or larger pulmonary artery.
Patients are eligible within 120 hours from diagnosis of the qualifying VTE
* Anticoagulation therapy with a therapeutic dose of DOAC for at least 6 months is indicated
* Able to provide written informed consent
Exclusion Criteria:
* Thrombectomy, insertion of a caval filter or use of a fibrinolytic agent to treat the current (index) DVT and/or PE
* More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH, fondaparinux, DOAC, or other anticoagulants
* An indication to continue treatment with therapeutic doses of an anticoagulant other than that VTE treatment prior to randomization (e.g., atrial fibrillation \[AF\], mechanical heart valve, prior VTE)
* Platelet count \<50,000/mm3 at the screening visit
* PE leading to hemodynamic instability (blood pressure \[BP\] \<90 mmHg or shock)
* Acute ischemic or hemorrhagic stroke or intracranial hemorrhage within the 4 weeks preceding screening
* Brain trauma or a cerebral or spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia within 4 weeks of screening
* Need for aspirin in a dosage of \>100 mg/day or any other antiplatelet agent alone or in combination with aspirin
* Primary brain cancer or untreated intracranial metastases at baseline
* Acute myeloid or lymphoid leukemia
* Bleeding requiring medical attention at the time of randomization or in the preceding 4 weeks
* Planned brain, spinal cord, cardiac, vascular, major thoracic and/or major abdominal surgery in the 4 weeks following randomization
* Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening
* Life expectancy \<3 months at randomization
* Calculated creatinine clearance (CrCl) \<30 mL/min (Cockcroft-Gault equation) at the screening visit
* Hemoglobin \<8 g/dL at the screening visit
* Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase (ALT) ≥3 x and/or bilirubin ≥2 x upper limit of normal (ULN) at the screening visit in absence of clinical explanation
* Uncontrolled hypertension (systolic BP\>180 mm Hg or diastolic BP \>100 mm Hg despite antihypertensive treatment)
* Women of child-bearing potential (WOCBP) who are unwilling or unable to use highly effective contraceptive measures during the study from screening up to 3 days after last treatment of apixaban or 100 days after administration of abelacimab (See Section 5.3.6. for highly effective contraceptive measures)
* Sexually active males with sexual partners of childbearing potential must agree to use a condom or other reliable contraceptive measure up to 3 days after last treatment of apixaban or 100 days after administration of abelacimab
* Pregnant or breast-feeding women
* Patients known to be receiving strong dual inducers or inhibitors of both CYP3A4 and P gp
* History of hypersensitivity to any of the study drugs (including apixaban) or excipients, to drugs of similar chemical classes, or any contraindication listed in the label for apixaban
* Subjects with any condition that in the Investigator's judgement would place the subject at increased risk of harm if he/she participated in the study
* Use of other investigational (not registered) drugs within 5 half-lives prior to enrollment or until the expected pharmacodynamic(s) (PD) effect has returned to baseline, whichever is longer. Participation in academic non-interventional studies or interventional studies, comprising testing different strategies or different combinations of registered drugs is permitted BIOLOGICAL: Abelacimab, DRUG: Apixaban
Venous Thromboembolism, Deep Venous Thrombosis, Pulmonary Embolism
Anticoagulants, VTE recurrence rate, PROBE design, LMWH, CAT, Cancer associated VTE, Abelacimab, Apixaban, FXI, Major bleeding events, CRNM bleeding events
A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE (MAGNOLIA)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT05171075
Inclusion Criteria:
* Male or female subjects ≥18 years old or other legal maturity age according to the country of residence
* Confirmed GI (colorectal, pancreatic, gastric, esophageal, gastro-esophageal junction or hepatobiliary) or confirmed GU (renal, ureteral, bladder, prostate, or urethra) cancers if:
* Unresectable, locally advanced, metastatic, or non-metastatic GI/GU cancer and
* No intended curative surgery during the study
* Confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT) (i.e., popliteal, femoral, iliac, and/or inferior vena cava vein thrombosis) and/or a confirmed symptomatic pulmonary embolism (PE), or an incidental PE in a segmental, or larger pulmonary artery. Patients are eligible within 120 hours from diagnosis of the qualifying VTE.
* Anticoagulation therapy with LMWH for at least 6 months is indicated
* Able to provide written informed consent
Exclusion Criteria:
* Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) occurrence of DVT and/or PE
* More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH, or other anticoagulants
* An indication to continue treatment with therapeutic doses of an anticoagulant other than for VTE treatment prior to randomization (e.g., atrial fibrillation, mechanical heart valve, prior VTE)
* PE leading to hemodynamic instability (systolic BP \<90 mmHg or shock).
* Acute ischemic or hemorrhagic stroke or intracranial hemorrhage, in the last 4 weeks preceding screening.
* Brain trauma, or cerebral or a spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia within 4 weeks of screening
* Need for aspirin in a dosage of more than 100 mg/day or, any other antiplatelet agent alone or in combination with aspirin
* Bleeding requiring medical attention at the time of randomization or in the preceding 4 weeks
* Planned brain, spinal cord, cardiac, vascular, major thoracic and/or major abdominal surgery in the 4 weeks following randomization
* History of heparin induced thrombocytopenia
* Infective acute or subacute endocarditis at the time of presentation
* Primary brain cancer or untreated intracranial metastasis
* Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening
* Life expectancy of \<3 months at randomization
* Calculated creatinine clearance (CrCl) \<30 mL/min at the screening visit
* Platelet count \<50,000/ mm3 at the screening visit
* Hemoglobin \<8 g/dL at the screening visit
* Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase ≥3 times and/or bilirubin ≥2 times the upper limit of normal (ULN) at the screening visit in the absence of clinical explanation
* Uncontrolled hypertension (systolic blood pressure \[BP\] \> 180 mm Hg or diastolic BP \>100 mm Hg despite antihypertensive treatment)
* Women of child-bearing potential (WOCBP) who are unwilling or unable to use highly effective contraceptive measures during the study from screening up to 3 days after last treatment of dalteparin or 100 days after administration of abelacimab
* Sexually active males with sexual partners of childbearing potential must agree to use a condom or other reliable contraceptive measure up to 3 days after last treatment of dalteparin or 100 days after administration of abelacimab
* Pregnant or breast-feeding women
* History of hypersensitivity to any of the study drugs (including dalteparin) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for dalteparin
* Subjects with any condition that in the judgement of the Investigator would place the subject at increased risk of harm if he/she participated in the study
* Use of other investigational (not-registered) drugs within 5 half-lives prior to enrollment or until the expected pharmacodynamic effect has returned to baseline, whichever is longer. Participation in academic non-interventional studies or interventional studies, comprising testing different strategies or different combinations of registered drugs is permitted. BIOLOGICAL: Abelacimab, DRUG: Dalteparin
Venous Thromboembolism, Deep Venous Thrombosis, Pulmonary Embolism
Anticoagulants, VTE recurrence rate, PROBE design, LMWH, CAT, Cancer associated VTE, GI cancer, Abelacimab, Dalteparin, GU cancer, FXI, Major bleeding events, CRNM bleeding events
Efficacy and Safety Studies of Frexalimab (SAR441344) in Adults With Relapsing Forms of Multiple Sclerosis (FREXALT)
clinicaltrials@northshore.org
ALL
18 years to 55 years old
PHASE3
NCT06141473
Inclusion Criteria:
* The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria.
* The participant has an EDSS score ≤5.5 at the first visit (Screening Visit)
* The participant must have at least 1 of the following prior to screening:
* ≥1 documented relapse within the previous year OR
* ≥2 documented relapses within the previous 2 years, OR
* ≥1 documented Gd enhancing lesion on an MRI scan within the previous year.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion Criteria:
* The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria
* The participant has a history of infection or may be at risk for infection:
* The presence of psychiatric disturbance or substance abuse.
* History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphosholipid syndrome and any participants requiring antithrombotic treatment.
* History or current hypogammaglobulinemia defined by values below the lower limit of normal (LLN).
* A history or presence of disease that can mimic MS symptoms, such as, but not limited to neuromyelitis optica spectrum disorder, systemic lupus erythematosus, Sjogren's syndrome, acute disseminated encephalomyelitis, and myasthenia gravis.
* The participant has had a relapse in the 30 days prior to randomization.
* The participant has contraindication for MRI, ie, presence of pacemaker, metallic implants in high risk areas (ie, artificial heart valves, aneurysm/vessel clips), presence of metallic material (eg, shrapnel) in high risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol scheduled MRI scans.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. DRUG: Frexalimab, DRUG: Teriflunomide, DRUG: Placebo infusion, DRUG: Placebo tablet, DRUG: MRI contrast-enhancing agents, DRUG: Cholestyramine, DRUG: Activated charcoal
Multiple Sclerosis
Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)
clinicaltrials@northshore.org
ALL
30 years and over
PHASE3
NCT05047172
Inclusion Criteria:
* Acute focal symptoms or signs of any duration associated with imaging, pathological, or other objective evidence of arterial infarction OR clinical evidence of cerebral, spinal cord, or retinal focal arterial ischemic injury based on symptoms persisting greater than or equal to 24 hours that occurred within 30 days prior to randomization
* Index stroke is attributed to 70-99% stenosis (or flow gap on MRA) of a major intracranial artery (carotid artery, middle cerebral artery (M1 or M2), vertebral artery (V4), basilar artery, posterior cerebral artery (P1), or anterior cerebral artery (A1)) documented by CTA, MRA, or catheter angiography
* Modified Rankin Scale score of ≤ 4, at time of consent
* Ability to swallow pills
* At least 30 years of age, inclusive, at time of consent
* Subjects 30-49 years of age are required to meet at least ONE of the following additional criteria below to qualify for the study:
• diabetes treated with insulin for at least 15 years
• at least 2 of the following atherosclerotic risk factors: hypertension (BP \> 140/90 or on antihypertensive therapy); dyslipidemia (LDL \> 130 mg /dl or HDL \< 40 mg/dl or fasting triglycerides \> 150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; any of the following vascular events occurring in a parent or sibling who was \< 55 years of age for men or \< 65 years of age for women at the time of the event: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery for atherosclerotic disease
• personal history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease
• any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic
• aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography
• any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic * Negative pregnancy test in a female who has had any menses in the last 18 months and has not had surgery that would make her unable to become pregnant * Subject is willing and able to return for all follow-up evaluations required by the protocol * Subject is available by phone * Subject understands the purpose and requirements of the study and can make him/herself understood * Subject has provided informed consent (use of a LAR is not permitted)
Exclusion Criteria:
* Previous treatment of qualifying intracranial artery with a stent, angioplasty, or other mechanical device, including mechanical thrombectomy for the qualifying stroke, or plan to perform one of these procedures
* Plan to perform concomitant endarterectomy, angioplasty or stenting of an extracranial vessel tandem to the symptomatic intracranial stenosis
* Intracranial tumor (except meningioma) or any intracranial vascular malformation
* Thrombolytic therapy within 24 hours prior to randomization
* Progressive neurological signs within 24 hours prior to randomization
* History of spontaneous non-traumatic intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural)
* Intracranial arterial stenosis due to: arterial dissection; MoyaMoya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with CSF pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process; reversible cerebral vasoconstriction syndrome (RCVS); suspected recanalized embolus
* Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, left atrial spontaneous echo contrast
* Known allergy or contraindication to aspirin, rivaroxaban, clopidogrel, or ticagrelor
* Uncontrolled severe hypertension (systolic pressure \> 180 mm Hg or diastolic pressure \> 115 mm Hg), active peptic ulcer disease, major systemic hemorrhage within 30 days prior to randomization, active bleed or bleeding diathesis, platelets \< 100,000, hematocrit \< 30, INR \> 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, severe liver impairment (AST or ALT \> 3 x normal, cirrhosis), or CrCl \< 15 mL/min or on dialysis
* Major surgery (including stenting of any vessel; open femoral, aortic, or carotid surgery; or cardiac surgery) within previous 30 days prior to randomization or planned in the next 90 days after randomization
* Any condition other than intracranial arterial stenosis that requires the subject to take any antithrombotic medication other than aspirin (NOTE: exceptions allowed for subcutaneous heparin or enoxaparin for deep vein thrombosis (DVT) prophylaxis)
* Dementia or psychiatric problem that prevents the subject from following an outpatient program reliably
* Co-morbid conditions that may limit survival to less than 12 months
* Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study, or currently breastfeeding
* Current or anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors or CYP3A4 substrates that cannot be stopped for the course of this study
* Enrollment in another study that would conflict with the current study DRUG: Ticagrelor + Aspirin, DRUG: Rivaroxaban + Aspirin, DRUG: Clopidogrel + Aspirin, OTHER: Risk Factor Management
Intracranial Arteriosclerosis, Stroke
SIMPLAAFY Clinical Trial (SIMPLAAFY)
clinicaltrials@northshore.org
ALL
18 years and over
NA
NCT06521463
Inclusion Criteria:
* Subject is of legal age to participate in the study per the laws of their respective geography.
* Subject is an acceptable candidate for a WATCHMAN FLX Pro device per the approved Instructions for Use.
* Subject is deemed to be suitable for all protocol defined drug regimens in the control and both test arms.
* The subject or legal representative is able to understand and willing to provide written informed consent to participate in the trial.
* The subject is able and willing to return for required follow-up visits and examinations.
Exclusion Criteria:
* Subject's device implant procedure was aborted (i.e., failed implant).
* Subject has a device margin residual leak \> 0mm at time of implant.
* Occurrence of complications (major bleeding, systemic embolism, stroke, pericardial effusion requiring intervention) during the implant procedure, post-procedure, or prior to randomization.
* Subject has a contraindication to one of the three protocol defined drug regimens.
* Subject requires long-term anticoagulation therapy for reason other than AF-related stroke risk reduction or requires chronic P2Y12 inhibitor therapy.
* Subject has known history of severe liver disease including cirrhosis with a Child-Pugh classification C or D.
* Subject with known hypercoagulability disorder, mechanical heart valve, rheumatic heart disease, or recurrent deep vein thrombosis.
* Subject has intracardiac thrombus, LAA sludge, or dense spontaneous echo contrast (SEC) observed during pre-implant imaging.
* Subject has Modified Rankin Score of ≥ 3 at baseline.
* Subject has left ventricular ejection fraction (LVEF) \< 30%.
* Subject with known amyloid cardiomyopathy.
* Platelet count ≤ 100,000 x 109/L.
* Subject has an estimated glomerular filtration rate (eGFR) \< 30 ml/min (chronic kidney disease stage IV or V) or is on dialysis.
* Subject has a stroke (of any cause, whether ischemic or hemorrhagic) within 30 days prior to implant or prior to randomization.
* Subject has a documented myocardial infarction (MI) as either a non-ST elevation MI (NSTEMI) or as an ST-elevation MI (STEMI), with or without intervention, within 30 days prior to implant or prior to randomization.
* Subject had or is planning to have any cardiac or non-cardiac intervention or surgical procedure within 30 days prior to or 6-months after implant (including, but not limited to, cardioversion, percutaneous coronary intervention, cardiac ablation, cataract surgery, etc.).
* Subject has a major bleeding event per International Society on Thrombosis and Haemostasis (ISTH) definitions within the 30 days prior to implant or prior to randomization. Lack of resolution of related clinical sequelae or planned and pending interventions to resolve bleeding/bleeding source are a further exclusion regardless of timing of the bleeding event.
* Subject has an active bleed.
* Subject has a cardiac tumor.
* Subject has signs/symptoms of acute or chronic pericarditis.
* Subject has an active infection.
* There is evidence of tamponade physiology.
* Subject has New York Heart Association Class IV congestive heart failure at the time of implant or prior to randomization.
* Subject is currently enrolled in another investigational study, except if the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatment.
* Subject is of childbearing potential and is, or plans to become, pregnant during the time of the study.
* Subject has a documented life expectancy of less than 12 months. DEVICE: WATCHMAN FLX Pro LAAC Device
Atrial Fibrillation, Stroke, Bleeding
A Study to Test the Effects and Safety of Riliprubart in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) for Which the Usual Treatments do Not Work (MOBILIZE)
clinicaltrials@northshore.org
ALL
18 years and over
PHASE3
NCT06290128
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
-Participant must have CIDP or possible CIDP criteria, based on European Academy of Neurology (EAN)/ Peripheral Nerve Society (PNS) Task Force CIDP guidelines, second revision (2021).
* Participant must have either typical CIDP, or one of the following two CIDP variants: motor CIDP (including motor predominant), multifocal CIDP (also known as Lewis Sumner Syndrome). Diagnosis must be confirmed by the adjudication committee.
* Participant must be refractory to either immunoglobulin therapy or corticosteroid therapy, as defined below.
* Immunoglobulinrefractory subgroup: Historic evidence of failure or inadequate response to immunoglobulin therapy prior to screening, defined as no clinically meaningful improvement or persistent INCAT score ≥2 after a minimum of:
* One dose of IVIg of 2 g/kg, followed by a second dose of 2 g/kg or two doses of 1 g/kg, with a separation of approximately 3 weeks between doses (each dose can be divided over 2 to 5 days), as indicated in the EAN/PNS 2021 guidelines OR
* SCIg maintenance therapy with at least 0.2 g/kg weekly for 5 weeks
* Corticosteroidrefractory subgroup:
Historic evidence of failure or inadequate response to corticosteroid therapy prior to screening, defined as no clinically meaningful improvement or persistent INCAT score ≥2 after a minimum of 12 weeks of corticosteroid therapy. Corticosteroid regimen can be daily oral prednisone/prednisolone, at least 60 mg, equivalent to methylprednisolone 48 mg, tapered over 6 to 8 months, or alternative regimens, e.g. pulsed high-dose corticosteroid treatment (40 mg/day oral dexamethasone or 500 mg/day IV methylprednisolone, each daily for 4 days per month for 6 months), as indicated in the EAN/PNS 2021 guidelines A clinically meaningful improvement is defined as one or more of the following:
* A ≥1 point decrease in adjusted INCAT disability score
* An increase in IRODS centile score ≥4 points
* An increase in MRC Sum score ≥3 points
* An improvement in hand grip strength of ≥8 kilopascals or
* Equivalent improvement based on information from medical records and per the Investigator's judgment
* Participant has an adjusted INCAT score of 2 to 9
--(a score of 2 should be exclusively from the leg disability component of INCAT).
* Any allowed immunosuppressant drugs (azathioprine, cyclosporine, or mycophenolate mofetil) have been taken for ≥6 months at a stable dose for ≥3 months prior to Screening
* Participant may be receiving low-dose oral corticosteroids (≤20 mg/day of prednisone \[or equivalent dose for other oral corticosteroids\]), but only if taken at a stable dose for ≥3 months prior to Screening
* Participant must have active disease, defined by a CIDP disease activity score (CDAS) of ≥ 2 points at Screening
* Participant must have documented vaccinations against encapsulated bacterial pathogens given within 5 years prior to Day 1 or initiated a minimum of 14 days prior to first dose of study intervention
* All participants must agree to use contraception methods during and after the study as required.
* Contraceptive use by men and women participating in the study should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 55 weeks after the last dose of study medication:
* Refrain from donating or cryopreserving sperm PLUS
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
* Must agree to use contraception/barrier as detailed below:
---- A male condom and an additional highly effective contraceptive method as described in the protocol.
-- A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
* Is a woman of nonchildbearing potential (WONCBP) as defined by the protocol OR
* Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective (with a failure rate of \<1% per year), as described in Appendix 10.4 Contraception and barrier guidance during the study intervention period (to be effective before starting the intervention) and for at least 55 weeks after the last administration of study intervention and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period.
* Body weight at Screening of 35 kg to 154 kg (77 to 340 lbs), inclusive
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
* Polyneuropathy of other causes, including but not limited to: hereditary demyelinating neuropathies, neuropathies secondary to infection or systemic disease, diabetic neuropathy, drug- or toxin-induced neuropathies, multifocal motor neuropathy, polyneuropathy related to Immunoglobulin M (IgM) monoclonal gammopathy, POEMS syndrome, and lumbosacral radiculoplexus neuropathy.
* Sensory CIDP, Distal CIDP and focal CIDP variants.
* Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments
* Poorly controlled diabetes (HbA1c \>7%)
* Serious infections requiring hospitalization within 30 days prior to Screening and any active infection requiring treatment during screening or presence of a condition that may predispose the participant to increased risk of infection (eg, medical history such as known immunodeficiency or history of recurrent infections)
* Clinical diagnosis of Systemic Lupus Erythematosus (SLE) or family history of SLE. For a participant with an antinuclear antibody (ANA) titer ≥1:160 and a positive anti-double-stranded DNA (anti-dsDNA) at Screening, SLE diagnosis must be ruled out prior to enrollment.
* Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Specifically, history of any hypersensitivity reaction to riliprubart or its components or of a severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibody.
* Any other clinically meaningful medical history or ongoing medical condition (as determined by the Investigator at Screening) that might impact benefitrisk assessment, jeopardize the safety of the participant, or compromise the quality of the data collected in this study; or history or presence of other significant concomitant illness that would adversely affect participation in this study, per Investigator's judgment.
* Documented history of attempted suicide over the 6 months prior to the Screening visit, presence of suicidal ideation of category 4 or 5 on CSSRS during screening, OR if in the Investigator's judgment, the participant is at risk for a suicide attempt.
* Evidence of CIDP worsening within the 6 weeks following a prior vaccination that, in the opinion of the Investigator, constituted a relapse
* Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk
* Participant has received immunoglobulins (IVIg or SCIg) within 8 weeks prior to Screening
* Treatment with plasma exchange within the 8 weeks prior to Screening
* Prior treatment with riliprubart
* Prior treatment with (any time) with highly immunosuppressive/chemotherapeutic medications with sustained effects, eg, mitoxantrone, alemtuzumab, cladribine
* Prior treatment (any time) with total lymphoid irradiation or bone marrow transplantation
* Prior treatment with B-cell-depleting agents such as rituximab within 6 months prior to riliprubart dosing, or until return of B-cells counts to normal levels, whichever is longer
* Use of any specific complement system inhibitor (eg, eculizumab) within 12 weeks or 5 times the halflife of the product, whichever is longer, prior to Screening
* Treatment within 6 months prior to dosing with immunosuppressive/ chemotherapeutic medications, such as cyclophosphamide, methotrexate, tacrolimus, interferon, or tumor necrosis factor (TNF)α inhibitors. Certain immunosuppressants commonly used in CIDP (azathioprine, cyclosporine, or mycophenolate mofetil) are allowed, as indicated under inclusion criterion.
* Any vaccination received within 28 days prior to dosing (with few exceptions to be confirmed at screening)
* Participation in another clinical trial with an investigational drug or receipt of an investigational product within 12 weeks or 5 times the halflife of the product, whichever is longer, prior to Screening
* Any screening laboratory values outside normal limits or abnormal ECG considered in the Investigator's judgment to be clinically significant in the context of this trial.
* Positive result of any of the following tests:
* hepatitis B surface antigen (HBsAg)
* antihepatitis B core antibodies (anti-HBc Ab) (unless anti-hepatitis B surface antibodies \[antiHBs Ab\] are also positive, indicating natural immunity)
* antihepatitis C virus (antiHCV) antibodies
* antihuman immunodeficiency virus 1 and 2 (antiHIV1 and antiHIV2) antibodies
* Pregnancy, defined as a positive result of a highly sensitive urine or serum pregnancy test, or lactation
* Accommodation in an institution because of regulatory or legal order; eg, imprisoned or legally institutionalized
* Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or potential risk for noncompliance to study procedures
* Participants are employees at the clinical study site or other individuals directly involved in the conduct of the study, or immediate family member of such individuals
* Any country related specific regulation that would prevent the participant from entering the study
* Treatment with efgartigimod within 8 weeks prior to screening DRUG: Riliprubart, DRUG: Placebo, DRUG: Riliprubart, DRUG: Placebo
Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Polyneuropathy, Inflammatory Demyelinating, Chronic
Autoimmune Diseases, Neurologic, Autoimmune Disorders, Nervous System, Peripheral Nerves Disease, Nervous System Diseases, Neurologic Disorders, Neurological Disorders, Complement Inhibitor, Complement Inhibitors
The CONFORM Pivotal Trial
clinicaltrials@northshore.org
ALL
18 years and over
NA
NCT05147792
Inclusion Criteria:
• Male or non-pregnant female aged ≥18 years
• Documented non-valvular AF (paroxysmal, persistent, or permanent)
• High risk of stroke or systemic embolism, defined as CHA2DS2-VASc score of ≥ 3
• Has an appropriate rationale to seek a non-pharmacologic alternative to long-term oral anticoagulation
• Deemed by the site investigator to be suitable for short term oral anticoagulation therapy but deemed less favorable for long-term oral anticoagulation therapy.
• Deemed appropriate for LAA closure by the site investigator and a clinician not a part of the procedural team using a shared decision-making process in accordance with standard of care
• Able to comply with the protocol-specified medication regimen and follow-up evaluations
• The subject (or legally authorized representative, where allowed) has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate institutional review board (IRB)/Regional Ethics Board (REB)/Ethics Committee (EC).
Exclusion Criteria:
• Pregnant or nursing patients and those who plan pregnancy in the period up to one year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7 days prior to index procedure.
• Anatomic conditions that would prevent performance of an LAA occlusion procedure (e.g., atrial septal defect (ASD) requiring closure, high-risk patent foramen ovale (PFO) requiring closure, a highly mobile inter-atrial septal aneurysm precluding a safe TSP, presence of a PFO/ASD closure device, history of surgical ASD repair or history of surgical LAAO closure)
• Atrial fibrillation that is defined by a single occurrence or that is transient or reversible (e.g., secondary thyroid disorders, acute alcohol intoxication, trauma, recent major surgical procedures)
• A medical condition (other than atrial fibrillation) that mandates long-term oral anticoagulation (e.g., history of unprovoked deep vein thrombosis or pulmonary embolism, or prosthetic mechanical heart valve)
• History of bleeding diathesis or coagulopathy, or patients in whom antiplatelet and/or anticoagulant therapy is contraindicated
• Documented active systemic infection
• Symptomatic carotid artery disease (defined as \>50% stenosis with symptoms of ipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke); if subject has a history of carotid stent or endarterectomy the subject is eligible if there is \<50% stenosis noted at the site of prior treatment
• Recent (within 30 days of index procedure) or planned (within 60 days post-procedure) cardiac or major non-cardiac interventional or surgical procedure
• Recent (within 30 days of index procedure) stroke or transient ischemic attack
• Recent (within 30 days of index procedure) myocardial infarction
• Vascular access precluding delivery of implant with catheter-based system
• Severe heart failure (New York Heart Association Class IV)
• Prior cardiac transplant, history of mitral valve replacement or transcatheter mitral valve intervention, or any prosthetic mechanical valve implant
• Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation)
• Platelet count \<75,000 cells/mm3 or \>700,000 cells/mm3, or white blood cell count \<3,000 cells/mm3
• Known allergy, hypersensitivity or contraindication to aspirin, heparin, or device materials (e.g., nickel, titanium) that would preclude any P2Y12 inhibitor therapy, or the patient has contrast sensitivity that cannot be adequately pre-medicated
• Actively enrolled or plans to enroll in a concurrent clinical study in which the active treatment arm may confound the results of this trial
• Unable to undergo general anesthesia
• Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol or protocol-specified medication regimen, confound the data interpretation, or is associated with a life expectancy of less than 5 years
• A condition which precludes adequate transesophageal echocardiographic assessment Echo exclusion criteria:
• Left atrial appendage anatomy which cannot accommodate a commercially available control device or the CLAAS Implant per manufacturer IFU (e.g., the anatomy and sizing must be appropriate for both the investigational (CLAAS) and a commercially available device in order to be enrolled in the trial)
• Intracardiac thrombus or dense spontaneous echo contrast consistent with thrombus, as visualized by TEE prior to implant
• Left ventricular ejection fraction (LVEF) \<30%
• Moderate or large circumferential pericardial effusion \>10 mm or symptomatic pericardial effusion, signs or symptoms of acute or chronic pericarditis, or evidence of tamponade physiology
• Atrial septal defect that warrants closure
• High risk patent foramen ovale (PFO), defined as an atrial septal aneurysm (excursion \>15 mm or length \> 15 mm) or large shunt (early \[within 3 beats\] and/or substantial passage of bubbles, e.g., \>20)
• Moderate or severe mitral valve stenosis (mitral valve area \<1.5 cm2)
• Complex atheroma with mobile plaque of the descending aorta and/or aortic arch
• Evidence of cardiac tumor
DEVICE: CLAAS, DEVICE: WATCHMAN left atrial appendage closure device / Amulet left atrial appendage occluder
Atrial Fibrillation, Stroke