Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III)

This study has been completed.
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Genentech, Inc.
Emissary International LLC
Information provided by (Responsible Party):
Daniel Hanley, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00784134
First received: October 31, 2008
Last updated: April 12, 2016
Last verified: April 2016

October 31, 2008
April 12, 2016
July 2009
July 2015   (final data collection date for primary outcome measure)
  • Modified Rankin Scale (Dichotomized 0-3) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Analysis modified on September 29, 2015 to account for adaptive randomization.
  • Modified Rankin Scale (Ordinal Scale) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Modified Rankin Scale (Dichotomized 0-4) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Random effects assessment of site effect (modified Rankin Scale 0-3) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Modified Rankin Scale (Longitudinal 0-3) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
Modified Rankin Scale [ Time Frame: 180 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00784134 on ClinicalTrials.gov Archive Site
  • All cause mortality [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Clot removal (Amount of residual blood) [ Time Frame: 72 h ] [ Designated as safety issue: No ]
  • Intensity of critical care management [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    As measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.
  • Safety/Mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality within 30 days.
  • Adverse and Serious Adverse Events [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
  • Predictors of Mortality using Cox Proportional Hazards Model [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
  • Sub-Group Analyses [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Assessment of mRS score 0-3 compared by race, gender, age, IVH size, and ICH location.
  • Functional Status [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
    Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group.
  • Quality of Life [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Assessment of SIS and EuroQol Visual Analog Scale by group.
  • All cause mortality [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Amount of residual blood [ Time Frame: 72 h ] [ Designated as safety issue: No ]
  • Intensity of critical care management [ Time Frame: 30 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III
Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III
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).
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Intraventricular Hemorrhage
  • Drug: Cathflo Activase
    1.0 mg of Cathflo Activase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
    Other Name: rt-PA
  • Other: Normal saline
    1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
  • Experimental: rt-PA
    administration of rt-PA via the intraventricular catheter
    Intervention: Drug: Cathflo Activase
  • Placebo Comparator: Saline Placebo
    1 ml of normal saline administered via the intraventricular catheter
    Intervention: Other: Normal saline
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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
500
January 2016
July 2015   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Brazil,   Canada,   Germany,   Hungary,   Israel,   Spain,   Switzerland,   United Kingdom
Puerto Rico
 
NCT00784134
IVH06
Yes
Not Provided
Not Provided
Daniel Hanley, Johns Hopkins University
Daniel Hanley
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Genentech, Inc.
  • Emissary International LLC
Study Chair: Daniel F. Hanley, MD Johns Hopkins University
Johns Hopkins University
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP