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Completed

NCT Number: NCT00784134

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).

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Key information

Conditions

Intraventricular Hemorrhage

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Sao Jose, Joinville, Joinville, Santa Catarina, Brazil

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

alteplase

Drug

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

Other names: Cathflo Activase, rt-PA

Normal Saline

Other

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

Primary outcomes

  1. Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis

    Time frame: 180 days

    Analysis modified on September 29, 2015 to account for adaptive randomization. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  2. Participant Score on the Modified Rankin Scale (mRS) - Ordinal Analysis

    Time frame: 180 days

    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  3. Participants With Modified Rankin Scale (mRS) <=4 - Dichotomized Analysis

    Time frame: 180 days

    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  4. Random Effects Assessment of Site Effect on Modified Rankin Scale (mRS) <= 3

    Time frame: 180 days

    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  5. Longitudinal Assessment of Participants With Modified Rankin Scale (mRS) <=3

    Time frame: 30 days and 180 days

    Comparing longitudinal modified Rankin Scale (mRS) scores 0-3 at Day 30 and Day 180. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Secondary outcomes

  1. All Cause Mortality

    Time frame: 180 days

  2. Clot Removal (Amount of Residual Blood)

    Time frame: 72 hours

    Change in blood volume measured between stability scan and end of treatment scan

  3. Intensity of Critical Care Management - Hospital Days

    Time frame: 30 days

    Intensity of critical care management 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.

  4. Intensity of Critical Care Management - ICU Days

    Time frame: 30 days

    Intensity of critical care management 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.

  5. Intensity of Critical Care Management - ICP Management

    Time frame: 30 days

    Intensity of critical care management 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.

  6. Intensity of Critical Care Management - Mechanical Ventilation

    Time frame: 30 days

    Intensity of critical care management 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.

  7. Intensity of Critical Care Management - Pressors

    Time frame: 30 days

    Intensity of critical care management 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.

  8. Intensity of Critical Care Management - Shunts

    Time frame: 30 days

    Intensity of critical care management 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.

  9. Intensity of Critical Care Management - All Infections

    Time frame: 30 days

    Intensity of critical care management 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.

  10. Intensity of Critical Care Management - Pneumonia

    Time frame: 30 days

    Intensity of critical care management 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.

  11. Intensity of Critical Care Management - All Infections

    Time frame: 180 days

    Intensity of critical care management 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.

  12. Safety/Mortality - Mortality Within 30 Days

    Time frame: 30 days

    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

  13. Safety/Mortality - Bacterial Brain Infections Within 30 Days

    Time frame: 30 days

    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

  14. Safety/Mortality - Systematic Bleeds Within 72 Hours

    Time frame: 72 hours

    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

  15. Safety/Mortality - Systematic Bleeds Within 30 Days

    Time frame: 30 days

    Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

  16. Adverse and Serious Adverse Events

    Time frame: 180 days

    Assessment of number of adverse and serious adverse events by treatment group.

  17. Predicting Hazards of Death by Treatment Group

    Time frame: 180 days

    Cox Proportional Hazards Model is used to predict the hazards ratio by treatment group.

  18. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (African-American)

    Time frame: 180 days

    Assessment of modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  19. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (White)

    Time frame: 180 days

    Assessment of modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  20. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Female)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  21. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Male)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  22. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (65 Years or Under)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  23. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (Over 65 Years)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  24. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Less Than 20ml)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  25. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (20-50ml)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  26. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Greater Than 50ml)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  27. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Thalamic)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  28. Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Non-Thalamic)

    Time frame: 180 days

    Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

  29. Functional Status - Barthel Index

    Time frame: 180 days

    Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The Barthel Index (BI) assesses ten functional tasks of daily living, and each task provides a measure for level of independence. Scores range from 0 and 100, with a higher score indicating greater independence.

  30. Functional Status - Participants With Extended Glasgow Outcome (eGOS) Score >=Upper Severe Disability

    Time frame: 180 days

    Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The extended Glasgow Outcome Scale (eGOS) is a global scale for functional outcome with eight categories: 1 - Death, 2 - Vegetative State, 3 - Lower Severe Disability, 4 - Upper Severe Disability, 5 - Lower Moderate Disability, 6 - Upper Moderate Disability, 7 - Lower Good Recovery, 8 - Upper Good Recovery.

  31. Functional Status - National Institutes of Health Stroke Scale (NIHSS)

    Time frame: 180 days

    Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The National Institutes of Health Stroke Scale (NIHSS) is a 15-item scale that assesses language, motor function, sensory loss, consciousness, visual fields, extraocular movements, coordination, neglect, and speech. It is scored from 0 (no stroke symptoms) to 42 (severe stroke).

  32. Quality of Life - Stroke Impact Scale (SIS) - Strength

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  33. Quality of Life - Stroke Impact Scale (SIS) - Mobility

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  34. Quality of Life - Stroke Impact Scale (SIS) - Hand Function

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  35. Quality of Life - Stroke Impact Scale (SIS) - Activities of Daily Living

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  36. Quality of Life - Stroke Impact Scale (SIS) - Communication

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  37. Quality of Life - Stroke Impact Scale (SIS) - Thinking

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  38. Quality of Life - Stroke Impact Scale (SIS) - Emotion

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  39. Quality of Life - Stroke Impact Scale (SIS) - Participation

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  40. Quality of Life - Stroke Impact Scale (SIS) - Recovery

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

  41. Quality of Life - EuroQol Visual Analogue Scale (EQ-VAS)

    Time frame: 180 days

    Assessment of SIS and EuroQol Visual Analog Scale by group. EuroQol Visual Analogue Scale (EQ-VAS) is a self-reported measure of health status. It is a marked scale where individuals draw a line to indicate their health, with end points of 0 (the worst health you can imagine) and 100 (the best health you can imagine).

Sponsors and collaborators

Lead sponsor

Johns Hopkins University

Other

Collaborators

  • Emissary International LLC
  • Genentech, Inc.
  • National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Acronym: CLEAR III

Important dates

Study start
2009
Primary completion
2015
Study completion
2016
First posted
Nov 3, 2008
Registry last updated
Dec 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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