Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

NCT ID: NCT00784134

Last Updated: 2018-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2016-01-31

Brief Summary

The overall objective of this Phase III clinical trial is to obtain information from a population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of current clinical practice and national demographics of ICH regarding the benefit (or lack thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS). This application requests funding for five years to initiate a Phase III randomized clinical trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA) with EVD+ placebo in the management and treatment of subjects with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH defined as ICH < 30 cc and obstruction of the 3rd or 4th ventricles by intraventricular blood clot).

Conditions

Intraventricular Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Alteplase

administration of alteplase via the intraventricular catheter

Group Type: EXPERIMENTAL

Alteplase

Intervention Type: DRUG

1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses

Saline Placebo

1 ml of normal saline administered via the intraventricular catheter

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: OTHER

1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses

Interventions

Alteplase

1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses

Intervention Type: DRUG

Normal saline

1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses

Intervention Type: OTHER

Other Intervention Names

Cathflo Activase; rt-PA

Eligibility Criteria

Inclusion Criteria

• Age 18-80
• Symptom onset less than 24 hrs prior to diagnostic CT scan
• Spontaneous ICH less than or equal to 30 cc or primary IVH
• IVH obstructing 3rd and/or 4th ventricles
• ICH clot stability at 6 hours or more post IVC placement
• IVH clot stability at 6 hours or more post IVC placement
• Catheter tract bleeding stability 6 hours or more post IVC placement
• EVD placed per standard medical care
• SBP less than 200 mmHg sustained for 6 hours prior to drug administration
• Able to randomize within 72 hours of diagnostic CT scan
• Historical Rankin of 0 or 1

Exclusion Criteria

• Suspected or untreated ruptured cerebral aneurysm, AVM, or tumor
• Presence of a choroid plexus vascular malformation or Moyamoya
• Clotting disorders
• Platelet count less than 100,000, INR greater than 1.4
• Pregnancy
• Infratentorial hemorrhage
• SAH at clinical presentation
• ICH/IVH enlargement that cannot be stabilized in the treatment time window
• Ongoing internal bleeding
• Superficial or surface bleeding
• 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
• Planned or simultaneous participation (between screening and Day-30) in another interventional medical investigation or clinical trial.
• No subject or legal representative to give written informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Emissary International LLC

INDUSTRY

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel F. Hanley, MD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Mayo Clinic, Arizona

Phoenix, Arizona, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of Southern California - Keck School of Medicine

Los Angeles, California, United States

University of California Los Angeles

Los Angeles, California, United States

Stanford University

Palo Alto, California, United States

Hartford Hospital

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Georgetown University

Washington D.C., District of Columbia, United States

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Intercoastal Medical Center

Sarasota, Florida, United States

University of South Florida

Tampa, Florida, United States

Rush University

Chicago, Illinois, United States

University of Illinois at Chicago

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Ruan Neurology Clinical and Research Center

Des Moines, Iowa, United States

University of Iowa

Iowa City, Iowa, United States

Kansas University Medical Center

Kansas City, Kansas, United States

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

St. Luke's Brain and Stroke Institute

Kansas City, Missouri, United States

Springfield Neurological and Spine Institute

Springfield, Missouri, United States

St. Louis University

St Louis, Missouri, United States

Cooper University Hospital

Camden, New Jersey, United States

New Jersey Neuroscience Institute at JFK

Edison, New Jersey, United States

University of Buffalo

Buffalo, New York, United States

Northshore University Hospital Long Island

Manhasset, New York, United States

Mount Sinai Hospital

New York, New York, United States

Columbia University

New York, New York, United States

SUNY Upstate Medical Center

Syracuse, New York, United States

Wake Forest University

Winston-Salem, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

Case-Western Reserve University Hospital

Cleveland, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Maine Medical Center

Portland, Oregon, United States

Providence Stroke Center

Portland, Oregon, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt

Nashville, Tennessee, United States

University of Texas, Southwestern, Dallas

Dallas, Texas, United States

University of Texas, Houston

Houston, Texas, United States

University of Texas, San Antonio

San Antonio, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Hospital Sao Jose, Joinville

Joinville, Santa Catarina, Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, , Brazil

Hospital de Pronto Socorro de Porto Alegre

Porto Alegre, , Brazil

Hospital de Clinicas de Ribeirao Preto

Ribeirão Preto, , Brazil

Hospital Sao Paulo Universidade Federal de Sao Paulo / UNIFESP

São Paulo, , Brazil

University of Alberta

Edmonton, Alberta, Canada

Montreal Neurological Institute at McGill University

Montreal, Quebec, Canada

University of Erlangen

Erlangen, , Germany

University of Halle

Halle, , Germany

University of Heidelberg

Heidelberg, , Germany

University of Leipzig

Leipzig, , Germany

University of Mainz

Mainz, , Germany

University of Tubingen

Tübingen, , Germany

University of Szeged

Szeged, Csongrád megye, Hungary

Honved Korhaz

Budapest, , Hungary

University of Debrecen

Debrecen, , Hungary

University of Pecs

Pécs, , Hungary

Rambam Medical Center

Haifa, , Israel

Hadassah Hebrew University Hospital

Jerusalem, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Sourasky Medical Center

Tel Aviv, , Israel

Bellvitge Hospital

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Vall d'Hebron University Hospital

Barcelona, , Spain

University of Zurich

Zurich, Canton of Zurich, Switzerland

University Hospital, Inselpital, Bern

Bern, , Switzerland

Salford Royal NHS Foundation Trust

Salford, Manchester, United Kingdom

Newcastle General Hospital

Newcastle upon Tyne, , United Kingdom

University of Southampton Hospital

Southampton, , United Kingdom

Countries

United States; Brazil; Canada; Germany; Hungary; Israel; Spain; Switzerland; United Kingdom

References

Roh DJ, Asonye IS, Carvalho Poyraz F, Magid-Bernstein JR, Joiner EF, Avadhani R, Awad I, Hanley DF, Ziai WC, Murthy SB. Intraventricular Hemorrhage Expansion in the CLEAR III Trial: A Post Hoc Exploratory Analysis. Stroke. 2022 Jun;53(6):1847-1853. doi: 10.1161/STROKEAHA.121.037438. Epub 2022 Jan 28.

Reference Type: DERIVED

PMID: 35086362 (View on PubMed)

Hansen BM, Ullman N, Muschelli J, Norrving B, Dlugash R, Avadhani R, Awad I, Zuccarello M, Ziai WC, Hanley DF, Thompson RE, Lindgren A; MISTIE and CLEAR Investigators. Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR III. Neurocrit Care. 2020 Oct;33(2):516-524. doi: 10.1007/s12028-020-00916-4.

Reference Type: DERIVED

PMID: 32026447 (View on PubMed)

Porter AL, Ebot J, Lane K, Mooney LH, Lannen AM, Richie EM, Dlugash R, Mayo S, Brott TG, Ziai W, Freeman WD, Hanley DF. Enhancing the Informed Consent Process Using Shared Decision Making and Consent Refusal Data from the CLEAR III Trial. Neurocrit Care. 2020 Feb;32(1):340-347. doi: 10.1007/s12028-019-00860-y.

Reference Type: DERIVED

PMID: 31571176 (View on PubMed)

Eslami V, Tahsili-Fahadan P, Rivera-Lara L, Gandhi D, Ali H, Parry-Jones A, Nelson LS, Thompson RE, Nekoobakht-Tak S, Dlugash R, McBee N, Awad I, Hanley DF, Ziai WC. Influence of Intracerebral Hemorrhage Location on Outcomes in Patients With Severe Intraventricular Hemorrhage. Stroke. 2019 Jul;50(7):1688-1695. doi: 10.1161/STROKEAHA.118.024187. Epub 2019 Jun 10.

Reference Type: DERIVED

PMID: 31177984 (View on PubMed)

Fam MD, Zeineddine HA, Eliyas JK, Stadnik A, Jesselson M, McBee N, Lane K, Cao Y, Wu M, Zhang L, Thompson RE, John S, Ziai W, Hanley DF, Awad IA; CLEAR III Trial Investigators. CSF inflammatory response after intraventricular hemorrhage. Neurology. 2017 Oct 10;89(15):1553-1560. doi: 10.1212/WNL.0000000000004493. Epub 2017 Sep 8.

Reference Type: DERIVED

PMID: 28887375 (View on PubMed)

Hanley DF, Lane K, McBee N, Ziai W, Tuhrim S, Lees KR, Dawson J, Gandhi D, Ullman N, Mould WA, Mayo SW, Mendelow AD, Gregson B, Butcher K, Vespa P, Wright DW, Kase CS, Carhuapoma JR, Keyl PM, Diener-West M, Muschelli J, Betz JF, Thompson CB, Sugar EA, Yenokyan G, Janis S, John S, Harnof S, Lopez GA, Aldrich EF, Harrigan MR, Ansari S, Jallo J, Caron JL, LeDoux D, Adeoye O, Zuccarello M, Adams HP Jr, Rosenblum M, Thompson RE, Awad IA; CLEAR III Investigators. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet. 2017 Feb 11;389(10069):603-611. doi: 10.1016/S0140-6736(16)32410-2. Epub 2017 Jan 10.

Reference Type: DERIVED

PMID: 28081952 (View on PubMed)

Webb AJ, Ullman NL, Morgan TC, Muschelli J, Kornbluth J, Awad IA, Mayo S, Rosenblum M, Ziai W, Zuccarrello M, Aldrich F, John S, Harnof S, Lopez G, Broaddus WC, Wijman C, Vespa P, Bullock R, Haines SJ, Cruz-Flores S, Tuhrim S, Hill MD, Narayan R, Hanley DF; MISTIE and CLEAR Investigators. Accuracy of the ABC/2 Score for Intracerebral Hemorrhage: Systematic Review and Analysis of MISTIE, CLEAR-IVH, and CLEAR III. Stroke. 2015 Sep;46(9):2470-6. doi: 10.1161/STROKEAHA.114.007343. Epub 2015 Aug 4.

Reference Type: DERIVED

PMID: 26243227 (View on PubMed)

Study Documents

Document Type: Data repository-VISTA

when available

View Document

Document Type: Study Protocol

when available

View Document

Document Type: Statistical Analysis Plan

when available

View Document

Related Links

http://braininjuryoutcomes.com

Related Info

Other Identifiers

5U01NS062851-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IVH06

Identifier Type: -

Identifier Source: org_study_id