Intraventricular Fibrinolysis for Aneurysmal Subarachnoid Hemorrhage.

NCT03187405 | Terminated Phase 3 DMC

• 1 other identifier: FIVHeMA
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Subarachnoid Hemorrhage

Keywords

Subarachnoid Hemorrhage; Intracranial Aneurysm; Cerebral Ischemia; Ventriculostomy; Tissue Plasminogen Activator

Outcome Measures

Primary Outcomes (1)

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

  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).

  6 months.

Secondary Outcomes (10)

• Death

  6 months

• DCI.

  6 weeks

• Clinical deterioration caused by DCI.

  1 month

• EVD obstruction.

  1 month

• Internal CSF shunt surgery.

  3 months

Study Arms (2)

EVD alone

NO INTERVENTION

In the EVD alone group group, the EVD will be managed as usual - i.e. will only be used to drain CSF.

EVD + IVF with Alteplase

EXPERIMENTAL

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

Interventions

EVD + IVF with Alteplase DRUG

Intraventricular fibrinolysis: Injection through the EVD of 1mg in 1 mL of Alteplase every eight hours during 3 days (9 doses).

Also known as: Intraventricular fibrinolysis with Alteplase

EVD + IVF with Alteplase

Eligibility Criteria

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

You may qualify if:

• 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.
• Oral information on research and informed consent of the patient and/or his relatives.

You may not qualify if:

• 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.
• Severe coagulopathy, including oral vitamin K antagonist.
• Pregnant or lactating woman.

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

University Hospital Of Caen

Caen, F-14000, France

Location

Related Publications (3)

• Etminan N, Beseoglu K, Eicker SO, Turowski B, Steiger HJ, Hanggi D. Prospective, randomized, open-label phase II trial on concomitant intraventricular fibrinolysis and low-frequency rotation after severe subarachnoid hemorrhage. Stroke. 2013 Aug;44(8):2162-8. doi: 10.1161/STROKEAHA.113.001790. Epub 2013 Jun 4.

  PMID: 23735957 BACKGROUND

• Goulay R, Flament J, Gauberti M, Naveau M, Pasquet N, Gakuba C, Emery E, Hantraye P, Vivien D, Aron-Badin R, Gaberel T. Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate. Stroke. 2017 Aug;48(8):2301-2305. doi: 10.1161/STROKEAHA.117.017014. Epub 2017 May 19.

  PMID: 28526764 BACKGROUND

• 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.

  PMID: 28081952 BACKGROUND

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Intracranial Aneurysm; Brain Ischemia

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Arterial Diseases; Aneurysm

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

Study Officials

• Thomas Gaberel, MD, PhD

  University Hospital, Caen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 6, 2017
• First Posted: June 15, 2017
• Study Start: February 21, 2018
• Primary Completion: February 5, 2024
• Study Completion: February 5, 2025
• Last Updated: July 25, 2025

Record last verified: 2025-07

Locations

FR (1)