Aneurysmal Subarachnoid HemorrhagePhase 2ASTROHNCT02501434
Aneurysmal Subarachnoid Hemorrhage Trial RandOmizing Heparin
A Phase 2 study testing Continuous Low-Dose IV Unfractionated Heparin Infusion in people with Aneurysmal Subarachnoid Hemorrhage and Neurobehavioral Manifestations, run by Robert F. James at 9 sites in United States.
Trial summary
A Blind-adjudication Multi-center Phase II Randomized Clinical Trial of Continuous Low-dose Intravenous Heparin Therapy in Coiled Low-grade Aneurysmal Subarachnoid Hemorrhage Patients with Significant Hemorrhage Burden. - STUDY IS TEMPORARILY SUSPENDED WITH PLAN TO RESUME SOON. NO SAFETY CONCERNS Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Aneurysmal Subarachnoid Hemorrhage, Neurobehavioral Manifestations, Vasospasm, Intracranial
- What is being tested?
- Continuous Low-Dose IV Unfractionated Heparin Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 9 sitesUnited States
- Study dates
- Apr 2016to 1 Jan 2024
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and ≤ 70 years
- Historical modified Rankin Scale Score 0-1
- Aneurysmal subarachnoid hemorrhage caused by a ruptured saccular aneurysm confirmed by catheter angiography that is repaired by endovascular coil embolization. Initiation of the coil embolization procedure should occur within 48 hours from the time of the aneurysm rupture (ictus). In patients where the exact time of the ictus is uncertain, a reasonable estimate of the time of ictus may be assigned. This reasonable time estimate should be considered likely accurate to within hours of the true unknown time.
- Quality of aneurysm embolization is interpreted to be Raymond-Roy Score of 1 (Complete) or 2 (Residual Neck) indicating that the aneurysm is adequately secured. A tiny amount of contrast in the body of the aneurysm is acceptable as long as the physician considers the aneurysm secured and to NOT represent a Raymond-Roy Score of 3 (Residual Aneurysm).
- WFNS grade 1 or 2 as assessed after repair of the aneurysm during screening but prior to randomization. A patient who presents with a WFNS greater than 2 who then improves with resuscitation, ventriculostomy, or time is acceptable.
- The pre-repair, admission head CT demonstrates an aSAH bleed pattern of "thick and diffuse" or "thick and focal" hemorrhage within the subarachnoid basal cisterns measuring ≥ 4 mm in the short axis and ≥ 20 mm in the long axis which is consistent with a modified Fisher grade 3 or 4. Intraventricular hemorrhage is acceptable. Enrollable patients must NOT have a parenchymal hemorrhage greater than 10 cc. Please refer to diagram below for examples. The hemorrhage location should be substantially within the supratentorial space and not isolated to the infratentorial space.
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- The location of the aneurysm should be the anterior circulation, posterior communicating, OR a basilar terminus (apex). Angiographic location of the aneurysm should be confirmed by catheter digital subtraction angiography (DSA) usually obtained during the coil embolization procedure. Patients with PICA or other posterior circulation aneurysms as the cause of the SAH should not be included because they typically cause primarily infratentorial bleed patterns.
- Ability to screen the patient and obtain a head CT 2-12 hours after the completion of the coiling procedure and the ability to initiate the study drug 12 ± 8 hours after the completion of aneurysm coiling procedure.
- After recovering from anesthesia following the aneurysm coiling procedure, the patient must remain a WFNS SAH grade ≤ 2 without evidence of a significant new focal neurological deficit including monoparesis / monoplegia, hemiparesis / hemiplegia, or receptive, expressive or global aphasia. New minor cranial nerve defect without any other new findings is permissible. If an NIHSS score was obtained prior to the aneurysm coiling procedure, a post-coiling (pre-enrollment) NIHSS score must not have increased by ≥ 4 points and GCS score must not be decreased by ≥ 2 points. The clinician at the local site should use their best clinical judgment as to whether a significant neurological decline has occurred due to the procedure.
- Patient is willing and able to return for study follow-up visits.
- Patient or their Legally Authorized Representative (LAR) has provided written informed consent.
Who cannot join
- Angio-negative SAH.
- History or imaging suggesting that the current hemorrhage presentation is a recent re-rupture of the aneurysm. Prior sentinel headache with negative CT or prior sentinel headache where the patient did not seek medical attention does not exclude the patient.
- Surgical Clipping (or plan for clipping) of the ruptured aneurysm or any non- ruptured aneurysm on the same admission.
- Aneurysm is identified to be traumatic, mycotic, blister or fusiform type by catheter DSA.
- Any intracranial stent placement or non-coil intra-aneurysmal device where dual- antiplatelet therapy is needed during admission.
- Patient has additional aneurysm(s) that are untreated and could reasonably be considered a possible alternate cause of the aSAH based on the observed bleeding pattern. Adequate treatment of these aneurysms by coiling embolization would result in the aneurysms no longer causing an exclusion. MRI may be used in some situations to determine that the associated aneurysms did not rupture based on lack of blood seen adjacent to the additional aneurysms.
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- Patient received heparin in any form within the last 100 days prior to current presentation / admission.
- Thrombocytopenia (platelet count less than 100,000 - assuming clumping has been ruled out as a cause).
- New intraparenchymal hemorrhage or new infarction larger the 15cc in volume, or significant increased mass effect as seen on the post-coiling, pre-enrollment head CT when compared to baseline admission head CT. New hyperdensity on CT scan related to contrast staining is not an exclusion.
- Patient has a documented history of heparin induced thrombocytopenia (HIT).
- Patient developed SAH-induced cardiac stunning prior to enrollment, with an ejection fraction <30%, or requiring IV medications for blood pressure maintenance.
- Concurrent significant intracranial pathology identified prior to enrollment, including but not limited to, Moyamoya disease, high suspicion or documented CNS vasculitis, severe fibromuscular dysplasia, arteriovenous malformation, arteriovenous fistula, or malignant brain tumor.
- Thrombolytic therapy within 24 hours prior to enrollment (rtPA, urokinase, etc.)
- Plan for antiplatelet or oral anticoagulation therapy from the time of the coil embolization procedure until 14 full days after enrollment. Antiplatelet therapy may be resumed after the 14-day window. A single 325 mg Aspirin (or lower dose) given during the coil embolization peri-procedural period is acceptable if this is the local standard of care but should be documented.
- Concomitant serious or uncontrolled disease such as severe infection, active (non- remission) cancer, severe organ dysfunction (severe heart failure, severe chronic kidney impairment requiring dialysis or severe chronic liver disease) or any coagulopathy (including DIC or bleeding diathesis).
- Uncontrollable hypertension (>180 systolic and/or >110 diastolic) that is not correctable prior to enrollment.
- Prior neurological disease/deficit or psychiatric disease that may continue to alter the results of neuropsychological evaluation, such as dementia, Multiple sclerosis, seizure disorder, severe traumatic brain injury, previous ruptured cerebral aneurysm or active major depression. Childhood seizures that have resolved and no longer require treatment are not part of this exclusion criteria.
- Active Immunosuppression therapy including chronic corticosteroid usage.
- History of gastrointestinal hemorrhage or major systemic hemorrhage within 30 days (including large flank or large retroperitoneal hematoma due to current admission coiling procedure requiring treatment), hemoglobin less than 6 g/dL, INR ≥1.5 after reversal of anticoagulants.
- Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days.
- Currently pregnant.
- Enrollment in another research study that prescribes a therapeutic treatment that differs from the local standard of care, or that would conflict with this study in some other significant fashion. Registries or coil comparison studies are appropriate.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Michigan
Ann Arbor, Michigan
Rush University
Chicago, Illinois
University of Texas Southwestern
Dallas, Texas
University of Florida
Gainesville, Florida
Indiana University
Indianapolis, Indiana, 46202
University of Louisville
Louisville, Kentucky, 40202
Yale University
New Haven, Connecticut
Mount Sinai Ichan School of Medicine
New York, New York
Tallahassee Neurological Clinic
Tallahassee, Florida
About this study
Official title: A Blind-adjudication Multi-center Phase II Randomized Clinical Trial of Continuous Low-dose Intravenous Heparin Therapy in Coiled Low-grade Aneurysmal Subarachnoid Hemorrhage Patients With Significant Hemorrhage Burden
A Blind-adjudication Multi-center Phase II Randomized Clinical Trial of Continuous Low-dose Intravenous Heparin Therapy in Coiled Low-grade Aneurysmal Subarachnoid Hemorrhage Patients with Significant Hemorrhage Burden. - STUDY IS TEMPORARILY SUSPENDED WITH PLAN TO RESUME SOON. NO SAFETY CONCERNS
Read the detailed description
The primary objective of this study is to investigate the safety and clinical effect of a continuous low-dose intravenous unfractionated heparin (LDIVH) infusion for the prevention of aneurysmal subarachnoid hemorrhage (aSAH) induced neurocognitive dysfunction and other delayed neurological deficits.
Additionally, increased blood and CSF levels of certain inflammatory biomarkers (IL-6, hsCRP, etc) have been correlated to aSAH patients with poor clinical outcomes. Unfractionated heparin (UFH) has known anti-inflammatory actions. As a result, a secondary objective of this study will be to evaluate whether LDIVH can reduce blood and CSF inflammatory biomarkers levels compared to controls and whether there is any association between inflammatory biomarker levels and cognitive outcomes in aSAH.
- Conditions
- Aneurysmal Subarachnoid Hemorrhage, Neurobehavioral Manifestations, Vasospasm, Intracranial, Intracranial Aneurysm, Heparin-induced Thrombocytopenia Type II
- Being tested
- Continuous Low-Dose IV Unfractionated Heparin Infusion
- Keywords
- aneurysmal subarachnoid hemorrhage, unfractionated heparin, neurobehavioral manifestations, delayed ischemic neurological deficits, cerebral aneurysm, coil embolization, Montreal Cognitive Assessment
- Medical subject headings
- Subarachnoid Hemorrhage, Neurobehavioral Manifestations, Vasospasm, Intracranial, Intracranial Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous Low-Dose IV Unfractionated Heparin InfusionDrug
Also called Heparin, Unfractionated Heparin, Heparin drip, IV Heparin
Continuous intravenous infusion of a low-dose unfractionated heparin drip
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Standard of Care |
| LDIVH (Unfractionated Heparin) | Experimental | Continuous Low-Dose IV Unfractionated Heparin Infusion Receives: Drug: Continuous Low-Dose IV Unfractionated Heparin Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montreal Cognitive Assessment (MoCA)
Primary Clinical Outcome Measure- mean score compared between groups
Measured: 90-day follow-up visit
Rate of "Major Bleeding" or "Clinically Relevant Non-Major Bleeding"
As defined by the International Society of Thrombosis and Heamostasis (ISTH) Primary Safety Outcome Measure-
Measured: Patients will be followed for the duration of the hospital stay; an expected average of 3 weeks
Secondary outcomes (25)
Rate of "Major Bleeding"
As defined by the International Society of Thrombosis and Haemostasis (ISTH)
Measured: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Rate of Type II Heparin Induced Thrombocytopenia (HIT)
Measured: Enrollment through 90-day follow-up visit
Rate of Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE)
Measured: Enrollment through 90-day follow-up visit
All Cause - Mortality Rate
Measured: Enrollment through 90-day follow-up visit
Incidence of Any Fever (> 38.3 degrees C; > or = 101.0 degrees F)
Measured: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of multiple fevers (> 2 episodes)
Measured: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Mean daily fever burden
Daily fever burden = Sum of hourly fever burden over 24 hours; Hourly fever burden = Any hourly temperature recording > 37 degrees C - (minus) 37 degrees C; if temperature is less than or equal to 37 degrees C then the hourly fever burden would be zero.
Measured: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Glasgow Coma Score
Measured: Enrollment, post-enrollment days #6, 10, discharge, and 90-day follow-up visit
National Institutes of Health Stroke Scale (NIHSS)
Measured: Enrollment, post-enrollment days #6, 10, upon discharge from hospital stay an expected average of about 3 weeks after admission, 90-day follow-up visit
Montreal Cognitive Assessment (MoCA)
Mean between groups and rate of MoCA score of 20 or less between groups
Measured: Enrollment, post-enrollment days #6, 10, 1 year follow-up
Center for Epidemiologic Studies Depression Scale (CES-D)
Measured: 90-day follow-up visit and 1-year follow-up visit
Trail Making Test Parts A&B
Measured: 90-day follow-up visit
Cerebral Vasospasm
Incidence of moderate and severe radiographic cerebral vasospasm (catheter angiogram, CTA, MRA) or incidence OR moderate and severe vasospasm by transcranial doppler (TCD) criteria
Measured: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of clinical cerebral vasospasm requiring rescue therapy
Rescue therapy = vasopressors or endovascular therapy for the purposes of reversing clinical vasospasm; it does not include Triple H (Hyperdynamic Therapy)
Measured: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of CT or MRI imaging demonstrating cerebral vasospasm related cerebral infarction
Measured: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Ordinal Regression Analysis of the modified Rankin Scale score (mRS)
Measured: 90-day follow-up visit and 1 year follow-up visit
Relative frequency of "good outcome" as defined by dichotomized mRS score 0-2
Measured: 90-day follow-up visit and 1 year follow-up visit
Barthel Index
Measured: 90-day follow-up visit and 1 year follow-up visit
Return to work status
Measured: 90-day follow-up and 1 year follow-up visit
Lawton instrumental activities of daily living (IADL)
Measured: 90-day follow-up visit and 1 year follow-up visit
Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS)
Measured: 90-day follow-up visit and 1 year follow-up visit
Checklist Individual Strength- Subscale Fatigue (CIS-F)
Measured: 90-day follow-up visit and 1 year follow-up visit
Plasma biomarker level (hsCRP)
Measured: Enrollment, post-enrollment days #2,4,6,10
Cerebrospinal Fluid (CSF) biomarker level (hsCRP)
Measured: Enrollment, post-enrollment days #2,4,6,10
Rate of Serious Adverse Events (SAEs)
Secondary Safety Outcome Measure
Measured: From enrollment through 90-Day follow-up visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2015 (estimated)
- Study startApr 2016
- Primary completionJan 2023 (estimated)
- Study completion1 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Aneurysmal Subarachnoid HemorrhageStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Robert F. James
- Sponsor type
- University, hospital or other
- Collaborators
- Indiana University
- Responsible party
- Sponsor-investigator, Robert F. James, Indiana University
- Investigators
- Robert F James, MD, Principal investigator, Indiana UniversityJ Marc Simard, MD, PhD, Principal investigator, University of MarylandJ Mocco, MD, MSc, Principal investigator, Icahn School of Medicine at Mount SinaiKevin N Sheth, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02501434
- Sponsor's protocol ID
- 10550
- Acronym
- ASTROH
- Status last verified
- Feb 2022
- First submitted
- 13 Jul 2015
- Last updated
- 4 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No: There is no plan to share data other than through publication or requests to Robert James by other investigators.
Publications
Simard JM, Schreibman D, Aldrich EF, Stallmeyer B, Le B, James RF, Beaty N. Unfractionated heparin: multitargeted therapy for delayed neurological deficits induced by subarachnoid hemorrhage. Neurocrit Care. 2010 Dec;13(3):439-49. doi: 10.1007/s12028-010-9435-1.
PubMed 20809188Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke. 2010 Aug;41(8):e519-36. doi: 10.1161/STROKEAHA.110.581975. Epub 2010 Jul 1.
PubMed 20595669Schweizer TA, Al-Khindi T, Macdonald RL. Mini-Mental State Examination versus Montreal Cognitive Assessment: rapid assessment tools for cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. J Neurol Sci. 2012 May 15;316(1-2):137-40. doi: 10.1016/j.jns.2012.01.003. Epub 2012 Jan 26.
PubMed 22280947Wong GK, Lam SW, Ngai K, Wong A, Mok V, Poon WS. Quality of Life after Brain Injury (QOLIBRI) Overall Scale for patients after aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2014 Jun;21(6):954-6. doi: 10.1016/j.jocn.2013.09.010. Epub 2013 Nov 9.
PubMed 24373816Hong CM, Tosun C, Kurland DB, Gerzanich V, Schreibman D, Simard JM. Biomarkers as outcome predictors in subarachnoid hemorrhage--a systematic review. Biomarkers. 2014 Mar;19(2):95-108. doi: 10.3109/1354750X.2014.881418. Epub 2014 Feb 5.
PubMed 24499240Romero FR, Bertolini Ede F, Figueiredo EG, Teixeira MJ. Serum C-reactive protein levels predict neurological outcome after aneurysmal subarachnoid hemorrhage. Arq Neuropsiquiatr. 2012 Mar;70(3):202-5. doi: 10.1590/s0004-282x2012000300009.
PubMed 22392113Fountas KN, Tasiou A, Kapsalaki EZ, Paterakis KN, Grigorian AA, Lee GP, Robinson JS Jr. Serum and cerebrospinal fluid C-reactive protein levels as predictors of vasospasm in aneurysmal subarachnoid hemorrhage. Clinical article. Neurosurg Focus. 2009 May;26(5):E22. doi: 10.3171/2009.2.FOCUS08311.
PubMed 19409001Tosun C, Kurland DB, Mehta R, Castellani RJ, deJong JL, Kwon MS, Woo SK, Gerzanich V, Simard JM. Inhibition of the Sur1-Trpm4 channel reduces neuroinflammation and cognitive impairment in subarachnoid hemorrhage. Stroke. 2013 Dec;44(12):3522-8. doi: 10.1161/STROKEAHA.113.002904. Epub 2013 Oct 10.
PubMed 24114458Simard JM, Aldrich EF, Schreibman D, James RF, Polifka A, Beaty N. Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment. J Neurosurg. 2013 Dec;119(6):1611-9. doi: 10.3171/2013.8.JNS1337. Epub 2013 Sep 13.
PubMed 24032706James RF, Shao EY, Page PS, Nazar RG, Martin LB, Dvorak J, Kanaan HK, Daniels MJ, Craycroft J, Rai SN, Everhart DE, Simard JM. Low-dose IV heparin preserves cognitive function in aneurysmal subarachnoid hemorrhage patients. [Unpublished Data]. Presented at AANS 82nd Annual Scientific Meeting. April 5-9, 2014. San Francisco, CA; Abstract #16572.
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Blind-adjudication Multi-center Phase II Randomized Clinical Trial of Continuous Low-dose Intravenous Heparin Therapy in Coiled Low-grade Aneurysmal Subarachnoid Hemorrhage Patients With Significant Hemorrhage Burden
- ClinicalTrials.gov ID
- NCT02501434
- Acronym / sponsor ID
- ASTROH / 10550
- Conditions
- Aneurysmal Subarachnoid Hemorrhage, Neurobehavioral Manifestations, Vasospasm, Intracranial, Intracranial Aneurysm, Heparin-induced Thrombocytopenia Type II
- Keywords
- aneurysmal subarachnoid hemorrhage, unfractionated heparin, neurobehavioral manifestations, delayed ischemic neurological deficits, cerebral aneurysm, coil embolization, Montreal Cognitive Assessment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Suspended
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- Robert F. JamesUniversity, hospital or other
- Collaborators
- Indiana University
- Study start
- Apr 2016 (actual)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- 1 Jan 2024 (estimated)
- First posted
- 17 Jul 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.
A Blind-adjudication Multi-center Phase II Randomized Clinical Trial of Continuous Low-dose Intravenous Heparin Therapy in Coiled Low-grade Aneurysmal Subarachnoid Hemorrhage Patients with Significant Hemorrhage Burden. - STUDY IS TEMPORARILY SUSPENDED WITH PLAN TO RESUME SOON. NO SAFETY CONCERNS
Detailed description
The primary objective of this study is to investigate the safety and clinical effect of a continuous low-dose intravenous unfractionated heparin (LDIVH) infusion for the prevention of aneurysmal subarachnoid hemorrhage (aSAH) induced neurocognitive dysfunction and other delayed neurological deficits.
Additionally, increased blood and CSF levels of certain inflammatory biomarkers (IL-6, hsCRP, etc) have been correlated to aSAH patients with poor clinical outcomes. Unfractionated heparin (UFH) has known anti-inflammatory actions. As a result, a secondary objective of this study will be to evaluate whether LDIVH can reduce blood and CSF inflammatory biomarkers levels compared to controls and whether there is any association between inflammatory biomarker levels and cognitive outcomes in aSAH.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Standard of Care |
| LDIVH (Unfractionated Heparin) | Experimental | Drug: Continuous Low-Dose IV Unfractionated Heparin InfusionContinuous Low-Dose IV Unfractionated Heparin Infusion |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 and ≤ 70 years
- Historical modified Rankin Scale Score 0-1
- Aneurysmal subarachnoid hemorrhage caused by a ruptured saccular aneurysm confirmed by catheter angiography that is repaired by endovascular coil embolization. Initiation of the coil embolization procedure should occur within 48 hours from the time of the aneurysm rupture (ictus). In patients where the exact time of the ictus is uncertain, a reasonable estimate of the time of ictus may be assigned. This reasonable time estimate should be considered likely accurate to within hours of the true unknown time.
- Quality of aneurysm embolization is interpreted to be Raymond-Roy Score of 1 (Complete) or 2 (Residual Neck) indicating that the aneurysm is adequately secured. A tiny amount of contrast in the body of the aneurysm is acceptable as long as the physician considers the aneurysm secured and to NOT represent a Raymond-Roy Score of 3 (Residual Aneurysm).
- WFNS grade 1 or 2 as assessed after repair of the aneurysm during screening but prior to randomization. A patient who presents with a WFNS greater than 2 who then improves with resuscitation, ventriculostomy, or time is acceptable.
Key exclusion criteria (22 listed)
- Angio-negative SAH.
- History or imaging suggesting that the current hemorrhage presentation is a recent re-rupture of the aneurysm. Prior sentinel headache with negative CT or prior sentinel headache where the patient did not seek medical attention does not exclude the patient.
- Surgical Clipping (or plan for clipping) of the ruptured aneurysm or any non- ruptured aneurysm on the same admission.
- Aneurysm is identified to be traumatic, mycotic, blister or fusiform type by catheter DSA.
- Any intracranial stent placement or non-coil intra-aneurysmal device where dual- antiplatelet therapy is needed during admission.
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 |
|---|---|---|
| Continuous Low-Dose IV Unfractionated Heparin InfusionAlso: Heparin, Unfractionated Heparin, Heparin drip, IV HeparinContinuous intravenous infusion of a low-dose unfractionated heparin drip | Drug | LDIVH (Unfractionated Heparin) |
Primary outcome
Montreal Cognitive Assessment (MoCA)
Time frame: 90-day follow-up visit
Primary Clinical Outcome Measure- mean score compared between groups
Rate of "Major Bleeding" or "Clinically Relevant Non-Major Bleeding"
Time frame: Patients will be followed for the duration of the hospital stay; an expected average of 3 weeks
As defined by the International Society of Thrombosis and Heamostasis (ISTH) Primary Safety Outcome Measure-
25 secondary outcomes
Rate of "Major Bleeding"
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Rate of Type II Heparin Induced Thrombocytopenia (HIT)
Time frame: Enrollment through 90-day follow-up visit
Rate of Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE)
Time frame: Enrollment through 90-day follow-up visit
All Cause - Mortality Rate
Time frame: Enrollment through 90-day follow-up visit
Incidence of Any Fever (> 38.3 degrees C; > or = 101.0 degrees F)
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of multiple fevers (> 2 episodes)
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Mean daily fever burden
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Glasgow Coma Score
Time frame: Enrollment, post-enrollment days #6, 10, discharge, and 90-day follow-up visit
National Institutes of Health Stroke Scale (NIHSS)
Time frame: Enrollment, post-enrollment days #6, 10, upon discharge from hospital stay an expected average of about 3 weeks after admission, 90-day follow-up visit
Montreal Cognitive Assessment (MoCA)
Time frame: Enrollment, post-enrollment days #6, 10, 1 year follow-up
Center for Epidemiologic Studies Depression Scale (CES-D)
Time frame: 90-day follow-up visit and 1-year follow-up visit
Trail Making Test Parts A&B
Time frame: 90-day follow-up visit
Cerebral Vasospasm
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of clinical cerebral vasospasm requiring rescue therapy
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of CT or MRI imaging demonstrating cerebral vasospasm related cerebral infarction
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Ordinal Regression Analysis of the modified Rankin Scale score (mRS)
Time frame: 90-day follow-up visit and 1 year follow-up visit
Relative frequency of "good outcome" as defined by dichotomized mRS score 0-2
Time frame: 90-day follow-up visit and 1 year follow-up visit
Barthel Index
Time frame: 90-day follow-up visit and 1 year follow-up visit
Return to work status
Time frame: 90-day follow-up and 1 year follow-up visit
Lawton instrumental activities of daily living (IADL)
Time frame: 90-day follow-up visit and 1 year follow-up visit
Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS)
Time frame: 90-day follow-up visit and 1 year follow-up visit
Checklist Individual Strength- Subscale Fatigue (CIS-F)
Time frame: 90-day follow-up visit and 1 year follow-up visit
Plasma biomarker level (hsCRP)
Time frame: Enrollment, post-enrollment days #2,4,6,10
Cerebrospinal Fluid (CSF) biomarker level (hsCRP)
Time frame: Enrollment, post-enrollment days #2,4,6,10
Rate of Serious Adverse Events (SAEs)
Time frame: From enrollment through 90-Day follow-up visit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2022.
- Background: PubMed 20809188Simard JM, Schreibman D, Aldrich EF, Stallmeyer B, Le B, James RF, Beaty N. Unfractionated heparin: multitargeted therapy for delayed neurological deficits induced by subarachnoid hemorrhage. Neurocrit Care. 2010 Dec;13(3):439-49. doi: 10.1007/s12028-010-9435-1.
- Background: PubMed 20595669Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke. 2010 Aug;41(8):e519-36. doi: 10.1161/STROKEAHA.110.581975. Epub 2010 Jul 1.
- Background: PubMed 22280947Schweizer TA, Al-Khindi T, Macdonald RL. Mini-Mental State Examination versus Montreal Cognitive Assessment: rapid assessment tools for cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. J Neurol Sci. 2012 May 15;316(1-2):137-40. doi: 10.1016/j.jns.2012.01.003. Epub 2012 Jan 26.
- Background: PubMed 24373816Wong GK, Lam SW, Ngai K, Wong A, Mok V, Poon WS. Quality of Life after Brain Injury (QOLIBRI) Overall Scale for patients after aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2014 Jun;21(6):954-6. doi: 10.1016/j.jocn.2013.09.010. Epub 2013 Nov 9.
- Background: PubMed 24499240Hong CM, Tosun C, Kurland DB, Gerzanich V, Schreibman D, Simard JM. Biomarkers as outcome predictors in subarachnoid hemorrhage--a systematic review. Biomarkers. 2014 Mar;19(2):95-108. doi: 10.3109/1354750X.2014.881418. Epub 2014 Feb 5.
- Background: PubMed 22392113Romero FR, Bertolini Ede F, Figueiredo EG, Teixeira MJ. Serum C-reactive protein levels predict neurological outcome after aneurysmal subarachnoid hemorrhage. Arq Neuropsiquiatr. 2012 Mar;70(3):202-5. doi: 10.1590/s0004-282x2012000300009.
- Background: PubMed 19409001Fountas KN, Tasiou A, Kapsalaki EZ, Paterakis KN, Grigorian AA, Lee GP, Robinson JS Jr. Serum and cerebrospinal fluid C-reactive protein levels as predictors of vasospasm in aneurysmal subarachnoid hemorrhage. Clinical article. Neurosurg Focus. 2009 May;26(5):E22. doi: 10.3171/2009.2.FOCUS08311.
- Background: PubMed 24114458Tosun C, Kurland DB, Mehta R, Castellani RJ, deJong JL, Kwon MS, Woo SK, Gerzanich V, Simard JM. Inhibition of the Sur1-Trpm4 channel reduces neuroinflammation and cognitive impairment in subarachnoid hemorrhage. Stroke. 2013 Dec;44(12):3522-8. doi: 10.1161/STROKEAHA.113.002904. Epub 2013 Oct 10.
- Background: PubMed 24032706Simard JM, Aldrich EF, Schreibman D, James RF, Polifka A, Beaty N. Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment. J Neurosurg. 2013 Dec;119(6):1611-9. doi: 10.3171/2013.8.JNS1337. Epub 2013 Sep 13.
- BackgroundJames RF, Shao EY, Page PS, Nazar RG, Martin LB, Dvorak J, Kanaan HK, Daniels MJ, Craycroft J, Rai SN, Everhart DE, Simard JM. Low-dose IV heparin preserves cognitive function in aneurysmal subarachnoid hemorrhage patients. [Unpublished Data]. Presented at AANS 82nd Annual Scientific Meeting. April 5-9, 2014. San Francisco, CA; Abstract #16572.
- Individual participant dataSharing planned: No. There is no plan to share data other than through publication or requests to Robert James by other investigators.
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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.
Robert F James, MD principal investigator
Indiana University
J Marc Simard, MD, PhD principal investigator
University of Maryland
J Mocco, MD, MSc principal investigator
Icahn School of Medicine at Mount Sinai
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Continuous Low-Dose IV Unfractionated Heparin Infusion in people with Aneurysmal Subarachnoid Hemorrhage and Neurobehavioral Manifestations, run by Robert F. James at 9 sites 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 11 inclusion and 22 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: paused, as of the sponsor's last update on 4 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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?
Results are not available in the source record.
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?
Montreal Cognitive Assessment (MoCA) (time frame: 90-day follow-up visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02501434, which also lists 10 linked publications.
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 4 Mar 2022.