StrokePhase 2ARTSS-IANCT02448069
Safety and Feasibility of Argatroban, Tissue Plasminogen Activator and Intra-arterial Therapy in Stroke
A Phase 2 study testing Argatroban in people with Stroke and Cerebral Ischemia, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial summary
Background: Our prior work with combination argatroban + recombinant tissue plasminogen activator (rt-PA) (ARTSS-1: Phase IIa low-dose safety study; n=65 and ARTSS-2: Phase IIb randomized low and high-dose study; n=90), demonstrated safety of the two drugs when delivered concomitantly and recanalization rates were… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Cerebral Ischemia
- What is being tested?
- Argatroban
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to Aug 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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. Symptoms must be distinguished from another ischemic event such as syncope, seizure, migraine, subarachnoid hemorrhage and hypoglycemia. If the patient reports awakening with the event, the time of onset should be considered as the last time the patient (or a witness to the patient's condition) considered herself/himself normal.
- Patients should meet local, institutional criteria to undergo emergent Endovascular Therapy (Intra-Arterial) to include:
- IAT must be able to begin before 6-hours of stroke onset or last seen well.
- CT-Angiogram confirmation of intra-arterial occlusion in any of the following locations: terminal ICA, MCA (M1 or M2 territories), PCA, distal vertebral or basilar artery.
- ASPECTS score on non-contrast head CT must be >/= 6.
Show all 10Show fewer
- IAT must be able to begin within 90 minutes of qualifying CT scan.
- Age >/= 18.
- Females of childbearing potential must have a negative pregnancy test prior to the administration of trial medication.
- Signed (written) informed consent by the patient or the patient's legal representative and/or guardian.
Who cannot join
- Evidence of intracranial hemorrhage (ICH) on baseline CT scan or diagnosis of a non-vascular cause of neurologic deficit.
- NIHSS Level of Consciousness score (1a) >/= 2.
- Pre-existing disability with mRS > 2.
- Any evidence of clinically significant bleeding, or known coagulopathy.
- INR >1.5.
- Patients with an elevated aPTT greater than the upper limit of normal (test can be repeated if investigator suspects a falsely elevated value such as when the collection tube is not completely filled).
Show all 27Show fewer
- Patients currently, or within the previous 24 hours, on an oral direct thrombin inhibitor (i.e., dabigatran), a factor 10a inhibitor (i.e., rivaroxaban, apixaban), or any other long-acting anticoagulant.
- Heparin flush required for an IV line. Line flushes with saline only.
- Any history of intra-cranial hemorrhage, known ateriovenous-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 (SBP > 185 mmHg or 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.
- Patients 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, UFH, LMWH, defibrinogenating agent, dextran, other direct thrombin inhibitors or thrombolytic agents, GPIIb/IIIa inhibitor or warfarin. [*Caveat: However, if in the judgment of the investigator a patient needs to be anticoagulated, but this can be deferred for 48 hours, then they could be included.]
- Currently participating or has participated in any investigational drug or device 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:
- Age >80
- Currently taking oral anticoagulants (regardless of INR)
- A history of stroke and diabetes.
- NIHSS > 25.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Health Science Center at Houston
Houston, Texas, 77030
About this study
Official title: ARTSS-IA: A Pilot, Phase IIa, Safety and Feasibility Study of ARgatroban in Combination With Recombinant Tissue Plasminogen Activator Stroke Study - Intra-Arterial
Background:
Our prior work with combination argatroban + recombinant tissue plasminogen activator (rt-PA) (ARTSS-1: Phase IIa low-dose safety study; n=65 and ARTSS-2: Phase IIb randomized low and high-dose study; n=90), demonstrated safety of the two drugs when delivered concomitantly and recanalization rates were greater than with historical controls. Further, interim analysis of neurological outcomes at 75 patients of the randomized Phase IIb trial, demonstrated a signal of efficacy when compared to control (rt-PA alone) patients. However, rt-PA fails to reperfuse brain in most patients with large thrombi, prompting several recent randomized clinical trials which have demonstrated that intra-arterial therapy (IA) following rt-PA substantially improves outcome in patients with distal carotid or proximal middle cerebral artery occlusions. As a result, rt-PA + IA has become the new standard-of-care for many patients with large arterial occlusions such as those treated in ARTSS-1 and 2. Therefore, this study is necessary to explore the feasibility and safety of adding Argatroban in acute ischemic stroke patients who also receive rt-PA followed by IA.
Read more
Primary Objective:
To demonstrate the feasibility and safety of treating stroke patients with Argatroban who undergo usual thrombolysis care (intravenous rt-PA followed by IA).
Secondary Objectives:
- Assess rates of ultra-early recanalization at commencement of IA;
- Assess the completeness and pattern of reperfusion as obtained by IA; 3) Assess clinical outcome
Read the detailed description
Design:
Prospective, single-arm, open-label, feasibility and safety Phase IIa study.
Study Population:
10 total ischemic stroke patients all treated with rt-PA (0-3 hour or 0-4.5 hour according to each site's local standard) and IA; age of 18 years or older; proximal (intracranial) artery occlusion as imaged by CT-angiogram (CTA).
Treatment:
All patients will receive standard-of-care intravenous rt-PA (0.9 mg/kg; maximum 90 mg) and IA. Before the end of the 1 hour rt-PA infusion, a 3.0 mcg/kg/min continuous infusion of Argatroban, preceded by a 100 mcg/kg bolus will be administered over 3-5 minutes. Infusion will be titrated to achieve an aPTT of 2.25 times baseline (not to exceed 10 mcg/kg/min) for a maximum of 12 hours.
Assessments:
- Baseline: History and physical exam, vital signs, CBC, liver function tests, PT/INR, PTT, non-contrast head CT, CT-Angiogram, NIHSS, mRS, concomitant medications. Laboratory results must be reported before study drug administration.
- 0-24 hours: Vital signs, aPTT (scheduled 2, 6, 12 hours), NIHSS (24-hours), conventional angiography as part of usual care intra-arterial therapy. Repeat parenchymal brain imaging (non-contrast head CT or MRI) at 24 hours from rt-PA bolus. Laboratory testing work (same as baseline).
- Day 7/Discharge (whichever occurs first): Vital signs, mRS, NIHSS
- Day 90: mRS (obtained by certified rater).
- Conditions
- Stroke, Cerebral Ischemia
- Being tested
- Argatroban
- Medical subject headings
- Stroke, Brain Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArgatrobanDrug
All patients will receive a 3.0 mcg/kg/min continuous infusion of Argatroban, preceded by a 100 mcg/kg bolus. Infusion will be titrated to achieve an aPTT of 2.25 times baseline (not to exceed 10 mcg/kg/min) for a maximum of 12 hours.
| Study group | Role | What they receive |
|---|---|---|
| Argatroban treatment | Experimental | Intravenous Argatroban delivered at 100mcg/kg bolus, then 12-hour infusion initiated at 3mcg/kg/min. Receives: Drug: Argatroban |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as measured by the incidence (absolute number) of symptomatic intracranial hemorrhage (sICH)
defined as:
- Any evidence of bleeding on brain imaging that is associated with clinically significant neurological worsening (Greater or equals 4 NIH stroke scale points) and
- Parenchymal Hemorrhage 2 (PH-2); evidence of confluent hemorrhage on brain imaging that occupies > 30% of the volume of the infarct and produces significant mass effect.
Measured: 12-36 hours after rt-PA bolus.
Secondary outcomes (4)
Feasibility of combining Argatroban with usual care as measured by success of starting the study medication bolus before the end of rt-PA infusion. 1. CT to tPA time, 2. CT to groin-puncture compared to institutional stroke-center database
Measured: 0-12 hours after stroke onset or hospital presentation.
Safety as measured by the incidence (absolute number of cases) of: 1. Groin or retroperitoneal hematoma 2. Major systemic hemorrhage requiring transfusion 3. Arterial perforation or dissection
Measured: 0-48 hours after enrollment.
Rates and completeness of arterial reperfusion as measured by cerebral angiography. Assessed at time of diagnostic (first intracranial injection unilateral to the occlusive lesion) and at the termination of study procedure.
Measured: At the end of Intra-Arterial therapy procedure (usually <12 hours from enrollment)
A NIH Stroke Scale (NIHSS) assessment will be performed at baseline and repeated at 24 hours, 48 hours and Day 7/discharge (whichever comes first).
Measured: 24, 48 hours, and Day 7 after rt-PA treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2015 (estimated)
- Study startMay 2015
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew D. Barreto, MD, The University of Texas Health Science Center, Houston
- Investigators
- Andrew D Barreto, MD, MS, Principal investigator, UT HEalth Sicience Center, Houston Medical School, Department of Neurology, Stroke Team
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02448069
- Sponsor's protocol ID
- HSC-MS-15-0327
- Acronym
- ARTSS-IA
- Status last verified
- Jun 2017
- First submitted
- 11 May 2015
- Last updated
- 21 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ARTSS-IA: A Pilot, Phase IIa, Safety and Feasibility Study of ARgatroban in Combination With Recombinant Tissue Plasminogen Activator Stroke Study - Intra-Arterial
- ClinicalTrials.gov ID
- NCT02448069
- Acronym / sponsor ID
- ARTSS-IA / HSC-MS-15-0327
- Conditions
- Stroke, Cerebral Ischemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 19 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Our prior work with combination argatroban + recombinant tissue plasminogen activator (rt-PA) (ARTSS-1: Phase IIa low-dose safety study; n=65 and ARTSS-2: Phase IIb randomized low and high-dose study; n=90), demonstrated safety of the two drugs when delivered concomitantly and recanalization rates were greater than with historical controls. Further, interim analysis of neurological outcomes at 75 patients of the randomized Phase IIb trial, demonstrated a signal of efficacy when compared to control (rt-PA alone) patients. However, rt-PA fails to reperfuse brain in most patients with large thrombi, prompting several recent randomized clinical trials which have demonstrated that intra-arterial therapy (IA) following rt-PA substantially improves outcome in patients with distal carotid or proximal middle cerebral artery occlusions. As a result, rt-PA + IA has become the new standard-of-care for many patients with large arterial occlusions such as those treated in ARTSS-1 and 2. Therefore, this study is necessary to explore the feasibility and safety of adding Argatroban in acute ischemic stroke patients who also receive rt-PA followed by IA.
Primary Objective:
To demonstrate the feasibility and safety of treating stroke patients with Argatroban who undergo usual thrombolysis care (intravenous rt-PA followed by IA).
Secondary Objectives:
- Assess rates of ultra-early recanalization at commencement of IA;
- Assess the completeness and pattern of reperfusion as obtained by IA; 3) Assess clinical outcome
Detailed description
Design:
Prospective, single-arm, open-label, feasibility and safety Phase IIa study.
Study Population:
10 total ischemic stroke patients all treated with rt-PA (0-3 hour or 0-4.5 hour according to each site's local standard) and IA; age of 18 years or older; proximal (intracranial) artery occlusion as imaged by CT-angiogram (CTA).
Treatment:
All patients will receive standard-of-care intravenous rt-PA (0.9 mg/kg; maximum 90 mg) and IA. Before the end of the 1 hour rt-PA infusion, a 3.0 mcg/kg/min continuous infusion of Argatroban, preceded by a 100 mcg/kg bolus will be administered over 3-5 minutes. Infusion will be titrated to achieve an aPTT of 2.25 times baseline (not to exceed 10 mcg/kg/min) for a maximum of 12 hours.
Assessments:
- Baseline: History and physical exam, vital signs, CBC, liver function tests, PT/INR, PTT, non-contrast head CT, CT-Angiogram, NIHSS, mRS, concomitant medications. Laboratory results must be reported before study drug administration.
- 0-24 hours: Vital signs, aPTT (scheduled 2, 6, 12 hours), NIHSS (24-hours), conventional angiography as part of usual care intra-arterial therapy. Repeat parenchymal brain imaging (non-contrast head CT or MRI) at 24 hours from rt-PA bolus. Laboratory testing work (same as baseline).
- Day 7/Discharge (whichever occurs first): Vital signs, mRS, NIHSS
- Day 90: mRS (obtained by certified rater).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Argatroban treatment | Experimental | Drug: ArgatrobanIntravenous Argatroban delivered at 100mcg/kg bolus, then 12-hour infusion initiated at 3mcg/kg/min. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Disabling Ischemic stroke symptoms with onset < 3 hours treated with IV rt-PA by local standards*.
- Patients should meet local, institutional criteria to undergo emergent Endovascular Therapy (Intra-Arterial) to include:
- Age >/= 18.
- Females of childbearing potential must have a negative pregnancy test prior to the administration of trial medication.
- Signed (written) informed consent by the patient or the patient's legal representative and/or guardian.
Key exclusion criteria (27 listed)
- Evidence of intracranial hemorrhage (ICH) on baseline CT scan or diagnosis of a non-vascular cause of neurologic deficit.
- NIHSS Level of Consciousness score (1a) >/= 2.
- Pre-existing disability with mRS > 2.
- Any evidence of clinically significant bleeding, or known coagulopathy.
- INR >1.5.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ArgatrobanAll patients will receive a 3.0 mcg/kg/min continuous infusion of Argatroban, preceded by a 100 mcg/kg bolus. Infusion will be titrated to achieve an aPTT of 2.25 times baseline (not to exceed 10 mcg/kg/min) for a maximum of 12 hours. | Drug | Argatroban treatment |
Primary outcome
Safety as measured by the incidence (absolute number) of symptomatic intracranial hemorrhage (sICH)
Time frame: 12-36 hours after rt-PA bolus.
defined as: 1. Any evidence of bleeding on brain imaging that is associated with clinically significant neurological worsening (Greater or equals 4 NIH stroke scale points) and 2. Parenchymal Hemorrhage 2 (PH-2); evidence of confluent hemorrhage on brain imaging that occupies > 30% of the volume of the infarct and produces significant mass effect.
4 secondary outcomes
Feasibility of combining Argatroban with usual care as measured by success of starting the study medication bolus before the end of rt-PA infusion. 1. CT to tPA time, 2. CT to groin-puncture compared to institutional stroke-center database
Time frame: 0-12 hours after stroke onset or hospital presentation.
Safety as measured by the incidence (absolute number of cases) of: 1. Groin or retroperitoneal hematoma 2. Major systemic hemorrhage requiring transfusion 3. Arterial perforation or dissection
Time frame: 0-48 hours after enrollment.
Rates and completeness of arterial reperfusion as measured by cerebral angiography. Assessed at time of diagnostic (first intracranial injection unilateral to the occlusive lesion) and at the termination of study procedure.
Time frame: At the end of Intra-Arterial therapy procedure (usually <12 hours from enrollment)
A NIH Stroke Scale (NIHSS) assessment will be performed at baseline and repeated at 24 hours, 48 hours and Day 7/discharge (whichever comes first).
Time frame: 24, 48 hours, and Day 7 after rt-PA treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2017.
Related trials for Stroke
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Recruiting
Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
Stroke, Upper Extremity Paresis
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew D Barreto, MD, MS principal investigator
UT HEalth Sicience Center, Houston Medical School, Department of Neurology, Stroke Team
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Argatroban in people with Stroke and Cerebral Ischemia, run by The University of Texas Health Science Center, Houston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as measured by the incidence (absolute number) of symptomatic intracranial hemorrhage (sICH) (time frame: 12-36 hours after rt-PA bolus.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2017.