We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Randomized Controlled Trial of Argatroban With Tissue Plasminogen Activator (tPA) for Acute Stroke (ARTSS-2)

This study has been terminated.
(The study was halted prematurely at 90 of 105 planned patients due to the beneficial results of embolectomy clinical trials.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01464788
First Posted: November 4, 2011
Last Update Posted: May 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
The University of Texas Health Science Center, Houston
Information provided by (Responsible Party):
Andrew D. Barreto, MD, The University of Texas Health Science Center, Houston
  Purpose
Randomized controlled clinical trial to estimate overall treatment benefit (improvement in disability) among stroke patients treated with rt-PA who are randomized to also receive either low-dose Argatroban, high-dose Argatroban or neither.

Condition Intervention Phase
Ischemic Stroke Drug: Low Dose Argatroban Drug: High Dose Argatroban Drug: rt-PA (alteplase) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ARTSS-2: A Pilot, Phase 2b, Randomized, Multi-center Trial of Argatroban in Combination With Recombinant Tissue Plasminogen Activator for Acute Stroke

Resource links provided by NLM:


Further study details as provided by Andrew D. Barreto, MD, The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Number of Participants With 0 or 1 on Modified Rankin Scale [ Time Frame: 90 days ]
    Excellent functional outcome as measured by the number of patients with a 0 or 1 on the modified Rankin Scale (mRS) at day 90 as assessed by study personnel blinded to treatment.

  • Number of Participants With Symptomatic Intracranial Hemorrhage Within 48 Hours of tPA Administration [ Time Frame: 48-hours ]
    Symptomatic intracranial hemorrhage (sICH) is defined as any evidence of bleeding on CT scan that in the opinion of the treating physician and/or an independent safety monitor is associated with a clinically significant neurological worsening. A four or more point increase in the NIHSS score from baseline (or last score obtained prior to blood found on CT scan) to subsequent CT scan at the time of potential worsening can be used as a guide by the clinical investigator or safety monitor for what represents a significant worsening in neurologic status but sICH can include any worsening deemed significant by the clinical investigator or independent safety monitor.


Enrollment: 90
Study Start Date: October 2011
Study Completion Date: June 11, 2015
Primary Completion Date: June 11, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose Argatroban + rt-PA (alteplase)

100 micrograms/kilogram bolus, followed by 1 microgram/kilogram/minute IV infusion for 48 hours

and

rt-PA (alteplase) 0.9mg/kg (max dose 90mg) - 10% bolus, then 90% over 1-hour

Drug: Low Dose Argatroban
100 micrograms/kilogram bolus, followed by 1 microgram/kilogram/minute IV infusion for 48 hours and rt-PA (alteplase) 0.9mg/kg (max dose 90mg) - 10% bolus, then 90% over 1-hour
Other Name: Argatroban
Drug: rt-PA (alteplase)
rt-PA (alteplase) 0.9mg/kg (max dose 90mg) - 10% bolus, then 90% over 1-hour
Experimental: High dose Argatroban + rt-PA (alteplase)

100 micrograms/kilogram bolus, followed by 3 micrograms/kilogram/minute IV infusion for 48 hours

and

rt-PA (alteplase) 0.9mg/kg (max dose 90mg) - 10% bolus, then 90% over 1-hour

Drug: High Dose Argatroban
100 micrograms/kilogram bolus, followed by 3 micrograms/kilogram/minute IV infusion for 48 hours and rt-PA (alteplase) 0.9mg/kg (max dose 90mg) - 10% bolus, then 90% over 1-hour
Other Name: Argatroban
Drug: rt-PA (alteplase)
rt-PA (alteplase) 0.9mg/kg (max dose 90mg) - 10% bolus, then 90% over 1-hour
Active Comparator: rt-PA (alteplase)
rt-PA (alteplase) 0.9mg/kg (max dose 90mg) - 10% bolus, then 90% over 1-hour
Drug: rt-PA (alteplase)
rt-PA (alteplase) 0.9mg/kg (max dose 90mg) - 10% bolus, then 90% over 1-hour

Detailed Description:

Recombinant tissue plasminogen activator (rt-PA), the only proven treatment for acute ischemic stroke, fails to reperfuse brain in most patients with large thrombi. In our Phase 2a low-dose safety study (n=65), the two drugs appeared safe when delivered concomitantly and recanalization rates were greater than historical controls. This study will provide evidence-based hypotheses and data needed to design a larger definitive trial.

The purpose of this trial is to estimate overall treatment benefit (improvement in disability) among stroke patients treated with rt-PA who are randomized to also receive either low-dose Argatroban, high-dose Argatroban or neither.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Disabling Ischemic stroke symptoms with onset < 3 hours treated with IV rt-PA by local standards*.

    * or ≤ 4.5 hours according to local standard of care.

  • NIHSS ≥ 10* or any NIHSS with an intracranial clot should be demonstrated on neurovascular imaging (TCD or CTA) in any one of the following areas: distal internal carotid artery (ICA) carotid artery (CA), middle cerebral artery (MCA - M1 or M2), posterior cerebral artery (PCA - P1 or P2), distal vertebral or basilar artery.
  • TCD criteria: Thrombolysis in brain ischemia (TIBI) 0, 1, 2 or 3 - CT-Angiogram: thrombolysis in myocardial ischemia (TIMI) 0 or 1 * NIHSS ≥ 10, demonstration of clot on neuroimaging is not necessary (i.e., enrollment can proceed with non-contrast head CT alone), but if performed, a clot must be demonstrated.
  • For those patients who will undergo repeat CT-Angiogram at 2-3 hours, estimated glomerular filtration rate (eGFR) must be ≥ 60 mL/min/1.73m2.
  • Females of childbearing potential must have a negative serum pregnancy test (HCG) prior to the administration of trial medication.
  • Signed (written) informed consent by the patient or the patient's legal representative and/or guardian.

Exclusion Criteria:

  • Patients whom the treating physician is planning (or could plan) to treat with intra-arterial thrombolysis or other endovascular procedures (i.e., mechanical clot retrieval) aimed at recanalization.
  • Evidence of intracranial hemorrhage (ICH) on baseline CT scan or diagnosis of a non-vascular cause of neurologic deficit.
  • National institute health stroke scale (NIHSS) Level of Consciousness score (1a) ≥ 2.
  • Pre-existing disability with mRS ≥ 2.
  • CT scan findings of hypoattenuation of the x-ray signal (hypodensity) involving ≥ 1/3 of the MCA territory.
  • Any evidence of clinically significant bleeding, or known coagulopathy.
  • INR >1.5.
  • Patients with an elevated activated partial thromboplastin time (aPTT) greater than the upper limit of normal
  • Patients currently, or within the previous 24 hours, on an oral direct thrombin inhibitor (i.e., dabigatran).
  • Heparin flush required for an IV line. Line flushes with saline only.
  • Any history of intra-cranial hemorrhage, known arteriovenous -malformation or unsecured cerebral aneurysms.
  • Significant bleeding episode [e.g. gastrointestinal (GI) or urinary tract] within the 3 weeks before study enrollment.
  • Major surgery or serious trauma in last 2 weeks.
  • Patients who have had an arterial puncture at a non-compressible site, biopsy of parenchymal organ, or lumbar puncture within the last 2 weeks.
  • Previous stroke, myocardial infarction (MI), post myocardial infarction pericarditis, intracranial surgery, or significant head trauma within 3 months.
  • Uncontrolled hypertension [Systolic blood pressure (SBP) > 185 mmHg or diastolic blood pressure (DBP) >110 mmHg] that does not respond to intravenous anti-hypertensive agents.
  • Surgical intervention (any reason) anticipated within the next 48 hours.
  • Known history of clinically significant hepatic dysfunction or liver disease - including a current history of alcohol abuse.
  • Abnormal blood glucose <50 mg/dL (2.7 mmol/L).
  • History of primary or metastatic brain tumor.
  • Current platelet count < 100,000/mm3.
  • Life expectancy < 3 months.
  • Patient who, in the judgment of the investigator, needs to be on concomitant (i.e., during the Argatroban infusion) anticoagulants other than Argatroban, including any form of heparin, unfractionated heparin (UFH), low molecular weight heparin (LMWH), defibrinogenating agent, dextran, other direct thrombin inhibitors or thrombolytic agents, glycoprotein llb/llla (GPIIb/IIIa) inhibitor or warfarin.
  • Participated in any investigational study within 30 days before the first dose of study medication.
  • Known hypersensitivity to Argatroban or its agents.
  • Additional exclusion criteria if patient presents between 3-4.5 hours:

    1. Age >80
    2. Currently taking oral anticoagulants (regardless of INR)
    3. A history of stroke and diabetes.
    4. NIHSS > 25.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01464788


Locations
United States, Texas
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
Andrew D. Barreto, MD
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Andrew Barreto, MD The University of Texas Health Science Center, Houston
  More Information

Additional Information:
Publications:
Responsible Party: Andrew D. Barreto, MD, Assistant Professor of Neurology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01464788     History of Changes
Other Study ID Numbers: HSC-MS-11-0464
First Submitted: November 1, 2011
First Posted: November 4, 2011
Results First Submitted: January 26, 2017
Results First Posted: May 11, 2017
Last Update Posted: May 11, 2017
Last Verified: March 2017

Keywords provided by Andrew D. Barreto, MD, The University of Texas Health Science Center, Houston:
stroke
Argatroban
thrombin-inhibition
thrombolysis
anticoagulation

Additional relevant MeSH terms:
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Tissue Plasminogen Activator
Plasminogen
Argatroban
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anticoagulants
Platelet Aggregation Inhibitors