The Spot Sign for Predicting and Treating ICH Growth Study (STOP-IT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Cincinnati
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Cincinnati
ClinicalTrials.gov Identifier:
NCT00810888
First received: December 15, 2008
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to determine if computed tomography angiography can predict which individuals with intracerebral hemorrhage will experience significant growth in the size of the hemorrhage. For individuals who are at high risk for hemorrhage growth, the study will compare the drug recombinant activated factor VII (rFVIIa) to placebo to determine the effect of rFVIIa on intracerebral hemorrhage growth.


Condition Intervention Phase
Intracerebral Hemorrhage
Drug: recombinant activated factor VII
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Spot Sign for Predicting and Treating Intracerebral Hemorrhage Growth Study

Resource links provided by NLM:


Further study details as provided by University of Cincinnati:

Primary Outcome Measures:
  • Life-threatening thromboembolic complications defined as development of (1) acute myocardial ischemia; (2) acute cerebral ischemia; and (3) acute pulmonary embolism [ Time Frame: through day 4 after completion of study drug ] [ Designated as safety issue: Yes ]
  • The rate of hematoma growth among spot sign positive subjects at 24 hours, comparing subjects treated with rFVIIa to those treated with placebo. Hematoma growth will be defined as a > 33% or > 6 cc increase in volume. [ Time Frame: at 24 hours ] [ Designated as safety issue: No ]
  • The sensitivity and specificity of the spot sign for predicting hematoma growth [ Time Frame: Baseline head CT scan within 5 hours, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of other potentially study drug related thromboembolic complications such as deep venous thrombosis and elevations in troponin not associated with ECG changes [ Time Frame: through day 4 after completion of study drug ] [ Designated as safety issue: Yes ]
  • Ninety-day outcomes among spot positive subjects, dichotomized as modified Rankin Scale score of 0-4 verses 5-6, comparing subjects treated with rFVIIa to those treated with placebo [ Time Frame: 90 days (+/- 7 days) from time of study enrollment ] [ Designated as safety issue: No ]
  • The positive and negative predictive values of the spot sign and the accuracy of the site investigators for correct identification of the spot sign as compared to a blinded study neuroradiologist. [ Time Frame: Baseline head CT scan within 5 hours, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours. ] [ Designated as safety issue: No ]
  • Rate of total hemorrhage volume growth (hematoma + IVH) among spot-positive subjects. [ Time Frame: 24 hours (+/- 3 hours) from baseline CT scan ] [ Designated as safety issue: No ]

Estimated Enrollment: 184
Study Start Date: November 2010
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (or determined to be CTA "spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive either rFVIIa at 80 mcg/kg (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg) or a placebo .
Drug: recombinant activated factor VII
Participants will receive rFVIIa at 80 mcg/kg (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg).
Placebo Comparator: 2
Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (or determined to be CTA "spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive either rFVIIa at 80 mcg/kg or a placebo (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg).
Drug: placebo
An inactive substance (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg)
No Intervention: 3
Participants with ICH who are determined by CTA not to be at high risk for hemorrhage growth (determined to be CTA "spot sign" negative) will be enrolled into a prospective observational group.

Detailed Description:

Intracerebral hemorrhage (ICH)—breakage of a blood vessel with bleeding in the brain—is a devastating form of stroke with a 40-50 percent fatality rate and no proven treatment. Because the majority of deaths from ICH occur within several days of the stroke, interventions for improving outcomes must occur early in the treatment course. Among the potentially modifiable determinants of ICH outcome, hematoma growth is a particularly attractive target for intervention and a major focus of this trial.

The purpose of this study is to determine if an imaging test called computed tomography angiography (CTA) can predict which individuals with ICH will experience significant growth in the size of the hemorrhage. Growth of the hemorrhage can cause additional injury and may worsen the outcome. For individuals who are at high risk for hemorrhage growth based on CTA results (i.e., a positive CTA "spot sign," evidence of contrast leakage within the hemorrhage), the study will compare the effects of a drug called recombinant activated factor VII (NovoSeven®) or rFVIIa with a placebo to determine which is better for reducing ICH growth.

The primary goals of this trial are (1) to determine the sensitivity and specificity of the CTA spot sign for predicting hematoma growth; (2) to determine the feasibility of using CTA to identify individuals with ICH who are at high risk of hematoma growth and to select study participants for randomization to treatment with rFVIIa or placebo; and (3) to determine the rate of hematoma growth among spot-positive individuals at 24 hours—comparing individuals treated with rFVIIa to those treated with placebo.

Approximately 184 persons with ICH will be enrolled in one of two study groups at 10 clinical sites across the United States and Canada. Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (CTA "spot sign" positive) will be randomized to receive either the active study medication, rFVIIa, at 80 mcg/kg, or to receive a placebo (an inactive substance). Participants with ICH who are determined by CTA not to be at high risk for hemorrhage growth (determined to be CTA "spot sign" negative) will be enrolled into a prospective observational group.

Duration of the study for participants is approximately 3 months.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute, spontaneous ICH (including bleeding in cerebellum) diagnosed by non-enhanced CT scan within five hours of symptom onset. (Time of onset is defined as the last time the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep)
  • Age >/= 18 years through 80 years (candidates must have had their 18th birthday, but not had their 81st birthday)
  • For spot positive patients, dosing of study drug within 90 minutes of enrolling CT scan

Exclusion Criteria:

  • Time of symptom onset of ICH is unknown or more than five hours prior to baseline CT scan,
  • ICH secondary to known or suspected trauma, aneurysm, vascular malformation, hemorrhagic conversion of ischemic stroke, venous sinus thrombosis, thrombolytic treatment of any condition (e.g., myocardial infarction, cerebral infarction, etc.), CNS tumor or CNS infection
  • Brainstem location of hemorrhage (patients with cerebellar hemorrhage may be enrolled)
  • Serum creatinine > 1.4 mg/dl (123 μmol/L). Sites that currently perform CTA as standard of care for ICH will follow their standard procedures regarding renal insufficiency.
  • Known allergy to iodinated contrast media
  • Intravenous or intra-arterial administration of iodinated contrast media within the previous 24 hours of baseline CT scan
  • Known hereditary (e.g., hemophilia) or acquired hemorrhagic diathesis, coagulation factor deficiency, or anticoagulant therapy with INR > 1.2
  • Known or suspected thrombocytopenia (unless current platelet count documented above 50,000 / μl)
  • Unfractionated heparin use with abnormal PTT
  • Low-molecular weight heparin use within the previous 24 hours
  • GPIIb/IIIa antagonist use in the previous two weeks
  • Glasgow Coma Scale score < 8 at time of proposed enrollment
  • Pre-admission modified Rankin Scale score > 2
  • Baseline ICH volume of < 0.5 cc (Hematoma volume will be estimated by local investigators from the baseline CT using the ABC / 2 method.)
  • Baseline ICH volume of > 90 cc
  • Planned surgical evacuation of ICH within 24 hours of symptom onset (placement of intraventricular catheter is not a contraindication to study enrollment.)
  • Evidence of acute or subacute ischemic stroke on baseline qualifying CT scan
  • Clinical history of thromboembolism or ischemic vascular disease, including myocardial infarction, coronary artery bypass surgery, cardiac angina, transient ischemic attack, ischemic stroke, peripheral artery disease (vascular claudication), cerebral bypass surgery, carotid endarterectomy, deep venous thrombosis, pulmonary embolism, or coronary or cerebrovascular angioplasty or stenting. (Clinically silent evidence of old ischemia on EKG (Q waves) or CT scan (silent old infarct) will not be considered reasons for exclusion.)
  • Baseline electrocardiogram shows evidence of acute cardiac ischemia (ST elevation in two contiguous leads, new LBBB, or ST depression)
  • Clinical history suggestive of acute cardiac ischemia (e.g., chest pain)
  • Abnormal baseline troponin
  • Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission
  • Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered
  • Recent (within 30 days) participation in any investigational drug or device trial or earlier participation in any investigational drug or device trial for which the duration of effect is expected to persist until the time of STOP-IT enrollment
  • Planned withdrawal of care or comfort care measures
  • Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency or psychological disorder)
  • Informed consent cannot be obtained from the patient or legally authorized representative
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810888

Contacts
Contact: Janice A. Carrozzella, MSN, APRN, CCRA 513-475-8793 Janice.carrozzella@uc.edu

Locations
United States, Arizona
St. Joseph's Hospital and Medical Center Recruiting
Phoenix, Arizona, United States, 85013
Contact: James L Frey, MD    602-679-5250    frey007@gmail.com   
United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92103
Contact: Thomas Hemmem, MD    619-543-7760    themmem@ucsd.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Joshua Goldstein, MD    617-726-7622    jgoldstein@partners.org   
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Peter D. Panagos, MD    314-747-6718    panagosp@wusm.wustl.edu   
United States, Ohio
University of Cincinnati—Clinical Coordinating Center Recruiting
Cincinnati, Ohio, United States, 45267-0525
Contact: Matthew Flaherty, MD    513-558-6609    matthew.flaherty@uc.edu   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-4283
Contact: Brett L. Cucchiara, MD    215-662-6738    cucchiar@mail.med.upen.edu   
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Maxim Hammer, MD    412-647-3030    hammmd@upmc.edu   
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Edward C. Jauch, MD, MS    843-792-5058    jauch@musc.edu   
Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada, T2N2T9
Contact: Andrew Demchuk, MD    403-944-8287    ademchuk@ucalgary.ca   
Canada, Ontario
Sunnybrook Health Science Center Recruiting
Toronto, Ontario, Canada, M4N3M5
Contact: David Gladstone, MD    416-480-4688    david.gladstone@sunnybrook.ca   
Sponsors and Collaborators
University of Cincinnati
Investigators
Principal Investigator: Matthew L. Flaherty, MD University of Cincinnati
Principal Investigator: Edward C. Jauch, MD, MS Primary Emergency Medicine Investigator, Medical University of South Carolina
  More Information

Additional Information:
No publications provided

Responsible Party: University of Cincinnati
ClinicalTrials.gov Identifier: NCT00810888     History of Changes
Other Study ID Numbers: P50NS044283_STOP_IT, 2P50NS044283-06
Study First Received: December 15, 2008
Last Updated: July 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Cincinnati:
intracerebral hemorrhage
ICH
computed tomography angiography
CTA
recombinant activated factor seven
rFVIIa
NovoSeven
recombinant activated factor VII

Additional relevant MeSH terms:
Cerebral Hemorrhage
Hemorrhage
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Hemorrhages
Nervous System Diseases
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on October 21, 2014