Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 83 of 195 for:    Hemorrhage AND SAH

Intraventricular Fibrinolysis for Aneurysmal Subarachnoid Hemorrhage. (FIVHeMA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03187405
Recruitment Status : Recruiting
First Posted : June 15, 2017
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Caen

Brief Summary:
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, with delayed cerebral ischemia (DCI) as a major complication. There are several evidences, both in preclinical and in clinical studies that intraventricular fibrinolysis (IVF) controls the phenomenon that are leading to DCI. Here, the investigators propose to conduct a phase III trial to provide a clear evaluation of the impact of IVF after aneurysmal SAH.

Condition or disease Intervention/treatment Phase
Subarachnoid Hemorrhage Drug: EVD + IVF with Alteplase Phase 3

Detailed Description:

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, which often causes acute hydrocephalus requiring the insertion of an external ventricular drain (EVD). A major complication of aneurysmal SAH is delayed cerebral ischemia (DCI), which corresponds to the occurrence of an ischemic stroke up to 21 days after the aneurysm rupture. There are currently only few ways to prevent it. As DCI is linked to the presence of blood within the subarachnoid space, it has been hypothesized that removing this blood may decrease the risk of DCI. It could be obtained by injecting a fibrinolytic agent through the EVD, a therapeutic strategy named intraventricular fibrinolysis (IVF). There are several evidences, both in preclinical and in clinical studies that IVF controls the phenomenon that are leading to DCI. It has notably been shown in Phase I and Phase II trial that IVF in aneurysmal SAH is safe and may decrease the risk of DCI, with a trend to improve the rate of good functional outcome by about 10%. Here, the investigators propose to conduct a phase III trial to provide a clear evaluation of the impact of IVF after aneurysmal SAH.

Materials and methods: this study will include patients with aneurysmal SAH requiring external ventricular drainage. The investigators will perform a pragmatic randomized controlled trial: compare the standard of care, i.e. the EVD alone, to the experimental treatment, i.e. IVF, with an open design. After exclusion of the aneurysm, patients will be randomly allocated to receive either EVD alone or EVD+IVF (72 hours, 9 doses). The primary outcome will be the proportion of patients without severe disability 6 months after the aneurysm rupture, as evaluated by the modified Rankin Scale (mRS). The investigators plan to include 440 patients, to show an increase of the rate of good functional outcome of 10% in the EVD+IVF group compared to the EVD alone group (α=0.05 and β=0.8). To obtain such sample, a multicenter trial is mandatory, and to date 16 centers accepted to participate. Each center will include one patient per month, and the inclusion period is to last 48 months.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: We plan to perform a pragmatic randomized controlled trial: compare the standard of care, i.e. the EVD alone, to the experimental treatment, i.e. IVF. As the standard treatment does not include injection within the EVD, the trial will not include injection through the EVD in the control group, so the trial will have an open design.
Masking: Single (Outcomes Assessor)
Masking Description: To minimize bias, the randomization and the treatment from V0 to the end of treatment will be performed by the local intensivist designed as investigator. The follow-up until day 4 (V1) to 6 months (V4), so the judgement criteria will be collected by the local neurosurgeon designed as investigator, who will be blinded to the treatment received.
Primary Purpose: Treatment
Official Title: Intraventricular Fibrinolysis Versus External Ventricular Drainage Alone in Aneurysmal Subarachnoid Hemorrhage: a Randomized Controlled Trial.
Actual Study Start Date : February 21, 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding
Drug Information available for: Alteplase

Arm Intervention/treatment
No Intervention: EVD alone
In the EVD alone group group, the EVD will be managed as usual - i.e. will only be used to drain CSF.
Experimental: EVD + IVF with Alteplase
Intraventricular fibrinolysis: Injection through the EVD of 1mg in 1 mL of Alteplase every eight hours during 3 days (9 doses).
Drug: EVD + IVF with Alteplase
Intraventricular fibrinolysis: Injection through the EVD of 1mg in 1 mL of Alteplase every eight hours during 3 days (9 doses).
Other Name: Intraventricular fibrinolysis with Alteplase




Primary Outcome Measures :
  1. Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis. [ Time Frame: 6 months. ]
    Proportion of patients without severe disability evaluated by the modified Rankin Scale (0-3). 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).


Secondary Outcome Measures :
  1. Death [ Time Frame: 6 months ]
    Risk of death

  2. DCI. [ Time Frame: 6 weeks ]
    The presence of cerebral infarction on CT or MR scan on the latest CT or MR scan made before death within 6 weeks, not present on the CT or MR scan between 24 and 48 hours after early aneurysm occlusion, and not attributable to other causes such as surgical clipping or endovascular treatment.

  3. Clinical deterioration caused by DCI. [ Time Frame: 1 month ]
    Occurrence of focal neurological impairment (such as hemiparesis, aphasia, apraxia, hemianopia, or neglect), or a decrease of at least 2 points on the Glasgow Coma Scale. This should last for at least 1 hour, is not apparent immediately after aneurysm occlusion, and cannot be attributed to other causes by means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies

  4. EVD obstruction. [ Time Frame: 1 month ]
    Numbers of permanent catheter obstruction requiring the insertion of a new catheter.

  5. Internal CSF shunt surgery. [ Time Frame: 3 months ]
    Rate of internal CSF shunt surgery.

  6. Rebleeding. [ Time Frame: 4 days ]
    A new ICH identified on a CT-scan performed after IVF that was not present before IVF.

  7. Catheter related infection. [ Time Frame: 3 month ]
    Clinical picture of infection associated with a positive CSF culture.

  8. Rate of patients who returned to work. [ Time Frame: 6 months ]
    Proportion of patient who returned to their previous professional activity.

  9. Quality of life evaluated by the MOS SF-36 scale [ Time Frame: 6 months ]
    MOS SF-36 scale

  10. Asthenia. [ Time Frame: 6 months ]
    Asthenia scale of Pichot



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients (age 18-75) with SAH on initial CT-Scan examination.
  • SAH associated with hydrocephalus requiring external ventricular drainage.
  • Confirmation of an associated intracranial aneurysm by vascular imaging.
  • Time from onset to admission under 24 hours.
  • Exclusion of the aneurysm by surgical clipping or endovascular coiling before IVF.
  • Oral information on research and informed consent of the patient and/or his relatives.

Exclusion Criteria:

  • Patient with severe clinical presentation on admission: WFNS score = 5.
  • Associated intracerebral hematoma of more than 2 cm in its larger width.
  • SAH diagnosed on lumbar puncture: original Fisher grade = 1.
  • Impossibility to exclude the aneurysm within 72 hours following its rupture.
  • Patient previously treated with antiplatelet therapy or treated with antiplatelet therapy after the aneurysm exclusion.
  • Severe coagulopathy, including oral vitamin K antagonist.
  • Pregnant or lactating woman.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03187405


Contacts
Layout table for location contacts
Contact: Thomas Gaberel, MD, PhD +33231065489 gaberel-t@chu-caen.fr

Locations
Layout table for location information
France
University Hospital Of Caen Recruiting
Caen, France, F-14000
Contact: Thomas Gaberel, MD, PhD    0231065489    gaberel-t@chu-caen.fr   
Contact: Francois Fournel, MD    0231065488    fournel-f@chu-caen.fr   
Sponsors and Collaborators
University Hospital, Caen
Investigators
Layout table for investigator information
Study Chair: Thomas Gaberel, MD, PhD University Hospital, Caen

Publications:
Layout table for additonal information
Responsible Party: University Hospital, Caen
ClinicalTrials.gov Identifier: NCT03187405     History of Changes
Other Study ID Numbers: FIVHeMA
First Posted: June 15, 2017    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Caen:
Subarachnoid Hemorrhage
Intracranial Aneurysm
Cerebral Ischemia
Ventriculostomy
Tissue Plasminogen Activator

Additional relevant MeSH terms:
Layout table for MeSH terms
Subarachnoid Hemorrhage
Hemorrhage
Intracranial Hemorrhages
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action