The Spot Sign for Predicting and Treating ICH Growth Study

NCT00810888 | Completed Phase 2 Results DMC

• 2 other identifiers: P50NS044283_STOP_IT2P50NS044283
• Study Type: interventional
• Target: 92
• Locations: 2 countries
• Sites: 10

Brief Summary

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.

Conditions

Intracerebral Hemorrhage

Keywords

intracerebral hemorrhage; ICH; computed tomography angiography; CTA; recombinant activated factor seven; rFVIIa; NovoSeven; recombinant activated factor VII

Outcome Measures

Primary Outcomes (4)

• Number of Study Subjects With Life-threatening Thromboembolic Complications

  Thromboembolic complications are defined as development of (1) acute myocardial ischemia; or (2) acute cerebral ischemia; or (3) acute pulmonary embolism

  through day 4 after completion of study drug administration

• Number of Subjects With Hematoma Growth Among Spot Sign Positive Subjects at 24 Hours.

  Comparison of only the subjects with a positive spot sign with respect to a categorical measure of hematoma growth from baseline to 24 hours. the outcome of interest is the percent of subjects with hematoma growth \> 33% or \> 6 cc increase in volume, from baseline to 24 hours.

  From baseline to 24 hours

• The Sensitivity of the Spot Sign for Predicting Hematoma Growth

  The outcome measure is hematoma growth. Groups 2 and 3 only will be compared as Group 1 had administration of study drug which was hypothesized to reduce hematoma growth. Sensitivity was estimated. Sensitivity or true positive rate is defined as, the number of strokes correctly identified as spot positive according to the "gold standard" / the total number of strokes identified as spot positive

  Baseline head CT scan within 5 hours of stroke, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours.

• The Specificity of the Spot Sign for Predicting Hematoma Growth

  The outcome measure is hematoma growth. Groups 2 and 3 only will be compared as group 1 had administration of study drug which was hypothesized to reduce hematoma growth. Specificity was estimated. Specificity or true negative rate is defined as, the number of non-spot positive (spot negative) strokes according to the "gold standard" / the total number of strokes identified as not spot positive.

  Baseline head CT scan within 5 hours of stroke, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours.

Secondary Outcomes (4)

• Number of Participants With Other Potentially Study Drug Related Thromboembolic Complications Such as Deep Venous Thrombosis (DVT) and Elevations in Troponin Not Associated With ECG Changes

  through day 4 after completion of study drug

• Number of Spot Positive Subjects With 90-day Outcome of Modified Rankin Scale Score >= 5

  90 days (+/- 7 days) from time of study enrollment

• Number of Participants With Agreement Between the Clinical Site Radiologists and the Study Radiologist With Respect to Identification of a Positive Spot Sign or the Absence of Positive Spot Sign on CTA

  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.

• Percent Change in Total Hemorrhage Volume (Intracerebral Hemorrhage (ICH) Plus Intraventricular Hemorrhage (IVH)).

  24 hours (+/- 3 hours) from baseline CT scan

Study Arms (3)

Group 1-Recombinant activated factor VII

ACTIVE COMPARATOR

Participants with ICH determined by CTA to be high risk for hemorrhage growth ("spot sign" positive for contrast leakage within the brain hematoma) randomized to receive rFVIIa at 80 mcg/kg (max dose 21.3 mL).

Drug: recombinant activated factor VII

Group 2 - Placebo

PLACEBO COMPARATOR

Participants with ICH determined by CTA to be high risk for hemorrhage growth ("spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive placebo.

Drug: placebo

Group 3 - Observation Only Arm

NO INTERVENTION

Participants with ICHdetermined by CTA not to be at high risk for hemorrhage growth (CTA "spot sign" negative) enrolled into a prospective observational group.

Interventions

recombinant activated factor VII DRUG

Participants will receive rFVIIa at 80 mcg/kg (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg).

Group 1-Recombinant activated factor VII

placebo DRUG

An inactive substance (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg)

Group 2 - Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.), central nervous system (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 international normalized ration (INR) \> 1.2
• Known or suspected thrombocytopenia (unless current platelet count documented above 50,000 / μl)
• Unfractionated heparin use with abnormal partial thromboplastin time (PTT)
• Low-molecular weight heparin use within the previous 24 hours
• GPIIb/IIIa antagonist use in the previous two weeks
• Direct thrombin inhibitor or factor Xa inhibitor within the previous 48 hours
• 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".)

Sponsors & Collaborators

• University of Cincinnati: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (10)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

University of California, San Diego

San Diego, California, 92103, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Cincinnati-Clinical Coordinating Center

Cincinnati, Ohio, 45267-0525, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Calgary

Calgary, Alberta, T2N2T9, Canada

Location

Sunnybrook Health Science Center

Toronto, Ontario, M4N3M5, Canada

Location

Related Publications (1)

• Gladstone DJ, Aviv RI, Demchuk AM, Hill MD, Thorpe KE, Khoury JC, Sucharew HJ, Al-Ajlan F, Butcher K, Dowlatshahi D, Gubitz G, De Masi S, Hall J, Gregg D, Mamdani M, Shamy M, Swartz RH, Del Campo CM, Cucchiara B, Panagos P, Goldstein JN, Carrozzella J, Jauch EC, Broderick JP, Flaherty ML; SPOTLIGHT and STOP-IT Investigators and Coordinators. Effect of Recombinant Activated Coagulation Factor VII on Hemorrhage Expansion Among Patients With Spot Sign-Positive Acute Intracerebral Hemorrhage: The SPOTLIGHT and STOP-IT Randomized Clinical Trials. JAMA Neurol. 2019 Dec 1;76(12):1493-1501. doi: 10.1001/jamaneurol.2019.2636.

  PMID: 31424491 DERIVED

Related Links

• trial website

MeSH Terms

Conditions

Cerebral Hemorrhage

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Jane Khoury, Professor of Pediatrics
• Organization: Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center

jane.khoury@cchmc.org

513-636-2690

Study Officials

• Matthew L. Flaherty, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

• Edward C. Jauch, MD, MS

  Primary Emergency Medicine Investigator, Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 15, 2008
• First Posted: December 18, 2008
• Study Start: November 1, 2010
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: March 16, 2018
• Results First Posted: January 8, 2018

Record last verified: 2018-02

Locations

US (8); CA (2)