Clinical Trial on Treatment of Intraventricular Hemorrhage

NCT00650858 | Completed Phase 2 Results DMC

• 2 other identifiers: IVH05ISRCTN47341677
• Study Type: interventional
• Target: 52
• Locations: 4 countries
• Sites: 25

Brief Summary

The specific objective of this trial is to determine the lowest dose and dose frequency possible with the best pharmacokinetic and safety profile and it's ability to remove a blood clot from the ventricular system.

Conditions

Intraventricular Hemorrhage

Keywords

Intraventricular hemorrhage (IVH); rt-PA

Outcome Measures

Primary Outcomes (3)

• 30-day Mortality

  The number of subjects who died at or before the 30-day follow-up visit were determined as a measure of safety. If more than 50% of the subjects died at or before the 30-day follow-up visit, the study would have been stopped for full DSMB review.

  30 days

• Incidence of Bacterial Ventriculitis, Meningitis

  The incidence of bacterial ventriculitis/meningitis was recorded to determine the safety of intraventricular administration of rt-PA. If 30% or more subjects experienced this event, the study would have been stopped for full DSMB review.

  30 days

• Rate of Symptomatic Bleeding Events

  The rate of symptomatic brain bleeding events were recorded to determine the safety of intraventricular administrations of rt-PA. If 35% or more subjects experienced a symptomatic bleeding event prior to the 30-day follow-up visit, the study would have been stopped for a full DSMB review.

  30-days

Secondary Outcomes (5)

• Average Daily Percentage Clot Size Resolution Over the First 3 Days

  3 days

• 90 Day Follow-Up Modified Rankin Scale (mRS) Score

  90 days

• 90 Day Follow-Up Glasgow Outcome Scale (GOS) Score

  90 days

• 180 Day Follow-Up Modified Rankin Scale (mRS) Score

  180 days

• 180 Day Follow-Up Glasgow Outcome Scale (GOS) Score

  180 days

Study Arms (3)

0.3 mg rt-PA

ACTIVE COMPARATOR

In stage 1 of the protocol, dose finding, subjects were randomized to either this 0.3 mg dose arm or the 1.0 mg dose arm. Subjects in this arm (0.3 mg) received up to 8 doses of 0.3 mg rt-PA every 12 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Drug: tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

1.0 mg rt-PA

ACTIVE COMPARATOR

In stage 1 of the protocol, dose finding, subjects were randomized to either this 1.0 mg dose arm or the 0.3 mg dose arm. Subjects in this arm (1.0 mg) received up to 8 doses of 1.0 mg rt-PA every 12 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Drug: tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

1.0 mg Rt-PA q8h

EXPERIMENTAL

In stage 2 of the protocol, dose frequency, subjects received up to 8 doses of 1.0 mg of rt-PA (Cathflo) every 8 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Drug: tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

Interventions

tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo) DRUG

0.3 mg and 1.0 mg of rt-PA (Cathflo) were administered every 12 hours (dose finding) and every 8 hours (dose frequency) via the intraventricular catheter to treat intraventricular hemorrhage.

Also known as: rt-PA, Cathflo, Activase

0.3 mg rt-PA; 1.0 mg Rt-PA q8h; 1.0 mg rt-PA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75
• IVC placed as standard of care using less than or equal to 2 complete passes.
• Spontaneous ICH less than or equal to 30 cc.
• Able to receive first dose within 48 hours of CT scan diagnosing IVH (providing the time of symptom onset to diagnostic CT does not exceed 12 hours).
• Clot size measured on CT scan done 6 hours after IVC placement must be equal to the presentation clot size plus or minus 5 cc (as determined by the AxBxC)/2 method).
• ON stability CT scan either the 3rd or 4th ventricles are occluded with blood (no evidence of CSF flow on CT).
• SBP \< 200 mmHg sustained for 6 hours.
• Historical Rankin of 0 or 1.

You may not qualify if:

• Suspected or untreated aneurysm or AVM (unless ruled out by angiogram or MRA/MRI).
• Clotting disorders.
• Patients with platelet count \< 100,000, INR \> 1.7, PT \> 15s, or an elevated APTT.
• Pregnancy (positive pregnancy test).
• Infratentorial hemorrhage (i.e., parenchymal/posterior fossa hematoma; all cerebellar hematomas excluded).
• SAH (An angiogram should be obtained when the diagnostic CT scan demonstrates subarachnoid hemorrhage or any hematoma location or appearance not strongly associated with hypertension. If the angiogram does not demonstrate a bleeding source that accounts for the hemorrhage, the patient is eligible for the study).
• ICH enlargement during the 6-hour stabilization period (6 hour after IVC placement).
• Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts.
• Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention.
• Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis.
• Prior enrollment in the study.
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
• Participation in another simultaneous medical investigation or trial.

Sponsors & Collaborators

• Johns Hopkins University: lead
• FDA Office of Orphan Products Development: collaborator
• Genentech, Inc.: collaborator

Study Sites (25)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

CR Drew Medical Center

Los Angeles, California, 90059, United States

Location

Standford Medical Center

Palo Alto, California, 94394, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

University of Maryland Medical Systems

Baltimore, Maryland, 21202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

St. Louis University

St Louis, Missouri, 63110, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas HSC, San Antonio

San Antonio, Texas, 78229, United States

Location

University of Virginia, Charlottesville

Charlottesville, Virginia, 22908, United States

Location

INOVA Fairfax Medical Center

Fairfax, Virginia, 22042, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

University of Heidelberg

Heidelberg, 69120, Germany

Location

Newcastle General Hospital

Newcastle upon Tyne, NE4 6BE, United Kingdom

Location

Related Publications (6)

• Kornbluth J, Nekoovaght-Tak S, Ullman N, Carhuapoma JR, Hanley DF, Ziai W. Early Quantification of Hematoma Hounsfield Units on Noncontrast CT in Acute Intraventricular Hemorrhage Predicts Ventricular Clearance after Intraventricular Thrombolysis. AJNR Am J Neuroradiol. 2015 Sep;36(9):1609-15. doi: 10.3174/ajnr.A4393. Epub 2015 Jul 30.

  PMID: 26228884 DERIVED

• Ziai W, Moullaali T, Nekoovaght-Tak S, Ullman N, Brooks JS, Morgan TC, Hanley DF. No exacerbation of perihematomal edema with intraventricular tissue plasminogen activator in patients with spontaneous intraventricular hemorrhage. Neurocrit Care. 2013 Jun;18(3):354-61. doi: 10.1007/s12028-013-9826-1.

  PMID: 23463422 DERIVED

• Morgan TC, Dawson J, Spengler D, Lees KR, Aldrich C, Mishra NK, Lane K, Quinn TJ, Diener-West M, Weir CJ, Higgins P, Rafferty M, Kinsley K, Ziai W, Awad I, Walters MR, Hanley D; CLEAR and VISTA Investigators. The Modified Graeb Score: an enhanced tool for intraventricular hemorrhage measurement and prediction of functional outcome. Stroke. 2013 Mar;44(3):635-41. doi: 10.1161/STROKEAHA.112.670653. Epub 2013 Jan 31.

  PMID: 23370203 DERIVED

• Webb AJ, Ullman NL, Mann S, Muschelli J, Awad IA, Hanley DF. Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program. Stroke. 2012 Jun;43(6):1666-8. doi: 10.1161/STROKEAHA.112.650523. Epub 2012 Apr 3.

  PMID: 22474059 DERIVED

• Ziai WC, Muschelli J, Thompson CB, Keyl PM, Lane K, Shao S, Hanley DF. Factors affecting clot lysis rates in patients with spontaneous intraventricular hemorrhage. Stroke. 2012 May;43(5):1234-9. doi: 10.1161/STROKEAHA.111.641050. Epub 2012 Mar 1.

  PMID: 22382155 DERIVED

• Herrick DB, Ziai WC, Thompson CB, Lane K, McBee NA, Hanley DF. Systemic hematologic status following intraventricular recombinant tissue-type plasminogen activator for intraventricular hemorrhage: the CLEAR IVH Study Group. Stroke. 2011 Dec;42(12):3631-3. doi: 10.1161/STROKEAHA.111.625749. Epub 2011 Sep 22.

  PMID: 21940973 DERIVED

Related Links

• CLEAR III Website

MeSH Terms

Interventions

Tissue Plasminogen Activator; Fibrinolytic Agents

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Cardiovascular Agents; Therapeutic Uses; Hematologic Agents

Results Point of Contact

• Title: Daniel F. Hanley, MD
• Organization: Johns Hopkins University

dhanley@jhmi.edu

410-614-6996

Study Officials

• Daniel F Hanley, MD

  Johns Hopkins University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: April 2, 2008
• Study Start: February 1, 2004
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: December 11, 2017
• Results First Posted: July 17, 2012

Record last verified: 2017-11

Locations

GB (1); US (22); DE (1); CA (1)