Condition category
Circulatory System
Date applied
29/04/2010
Date assigned
29/04/2010
Last edited
14/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.braininjuryoutcomes.com

Contact information

Type

Scientific

Primary contact

Dr Barbara Gregson

ORCID ID

Contact details

Neurosurgical Trials Unit
Newcastle University
3-4 Claremont Terrace
Newcastle upon Tyne
NE2 4AE
United Kingdom

Additional identifiers

EudraCT number

2007-006006-22

ClinicalTrials.gov number

Protocol/serial number

6469

Study information

Scientific title

Acronym

MISTIE

Study hypothesis

Study population:
Stage 1 – Dose Finding: 60 patients with ICH (45 surgical and 15 medical, 3:1 randomisation). Tiers 1 and 2: MISTIE + rt-PA versus medical.
Stage 2 – Safety: 50 patients with ICH (25 surgical and 25 medical, 1:1 randomisation)

Objectives and purpose:
The purpose of this trial is to determine the safety of using a combination of minimally invasive surgery and clot lysis with rt-PA to remove ICH. The procedure is to use image-based surgery (magnetic resonance imaging [MRI] or computed tomography [CT]) to provide catheter access to ICH for the intervention, which is a one-time clot aspiration followed by instillation of rt-PA over approximately 72 hours. We propose to test if this intervention facilitates more rapid and complete recovery of function and decreased mortality from this condition compared to conventional medical management without subjecting the patient to craniotomy. The specific objective of this trial is to test the safety of this intervention and assess its ability to remove blood clot from brain tissue.

Ethics approval

MREC approved on the 14/01/2009 (ref: 08/H0906/158)

Study design

Randomised interventional treatment trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: Generic Health Relevance and Cross Cutting Themes, Stroke Research Network; Subtopic: Generic Health Relevance (all Subtopics); Disease: Surgery

Intervention

The neurosurgeon will review the stability CT scan to determine the burr hole location and trajectory to be used during the operative procedure to place the catheter. The Surgical Center personnel will review whether the proposed burr hole location and trajectory is appropriate or that a different location/trajectory is recommended. The catheter placement will be performed in either the operating room or the ICU. Careful hematoma aspiration is performed free hand using a 10 cc syringe.

Follow up length: 6 months
Study entry: single randomisation only

Intervention type

Other

Phase

Phase II/III

Drug names

Primary outcome measures

Mortality, 30 days and procedure related.

Secondary outcome measures

1. Cerebritis, meningitis
2. Clot size reduction, post-operative and by day 4 - 5
3. Glasgow Outcome Scale (GOS), extended GOS (eGOS), Rankin, Stroke Impact Scale (SIS), measured at 30, 90, 180, 270, 365 days
4. Symptomatic rebleeding

Overall trial start date

01/04/2010

Overall trial end date

01/12/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 - 80 years, either sex
2. Glasgow Coma Scale (GCS) less than 14 or a National Institutes of Health Stroke Scale (NIHSS) (including the use of distal hand measures) greater than 6
3. Spontaneous supratentorial ICH greater than 20 cc
4. Symptoms less than 12 hours prior to diagnostic CT scan (an unknown time of symptom onset is exclusionary)
5. Intention to initiate surgery within 48 hours after diagnostic CT
6. First dose can be given within 54 hours of diagnostic CT
7. Six-hour clot size equal to the most previous clot size + 5 cc (as determined by additional CT scan at least 6 hours after the initial stability scan (A*B*C)/2 method)
8. Systolic blood pressure (SBP) less than 200 mmHg sustained for 6 hours recorded closest to the time of randomisation
9. Historical Rankin score of 0 or 1
10. Negative pregnancy test

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 110

Participant exclusion criteria

1. Infratentorial hemorrhage including brainstem (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy)
2. Patients with platelet count less than 100,000, international normalised ratio (INR) greater than 1.7, or an elevated prothrombin time (PT) or activated partial thromboplastin time (APTT) (reversal of coumadin is permitted but the patient must not require coumadin during the acute hospitalisation). Irreversible coagulopathy either due to medical condition or prior to randomiation (patient must have a sustained INR less than 1.7 using short- and long-acting procoagulants [Novoseven, FFP, and/or vitamin K]).
3. Clotting disorders
4. Any concurrent serious illness that would interfere with the safety assessments including hepatic, renal, gastroenteroligic, respiratory, cardiovascular, endocrinologic, immunologic, and haematologic disease
5. Patients with a mechanical valve
6. Patients with unstable mass or evolving intracranial compartment syndrome
7. Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly
8. Greater than 80 years (higher incidence of amyloid)
9. Under 18 years of age (high incidence of occult vascular malformation)
10. Pregnant (positive pregnancy test) or lactating females (likelihood of altered coagulation function associated with the high oestrogen/progesterone state)
11. Irreversibly impaired brainstem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS less than or equal to 4
12. Historical Rankin score greater than or equal to 2
13. Intraventricular haemorrhage requiring external ventricular drainage
14. Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts
15. Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention
16. Known risk for embolisation, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis
17. In the investigator's opinion, the patient is unstable and would benefit from a specific intervention rather than supportive care plus or minus endoscopic or MIS+rtPA
18. Prior enrolment in the study
19. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
20. Participation in another simultaneous trial of ICH treatment

Recruitment start date

01/04/2010

Recruitment end date

01/12/2010

Locations

Countries of recruitment

Germany, United Kingdom

Trial participating centre

Neurosurgical Trials Unit
Newcastle upon Tyne
NE2 4AE
United Kingdom

Sponsor information

Organisation

Johns Hopkins University (USA)

Sponsor details

1550 Orleans Street
3M50 South
Baltimore
Maryland
21231
United States of America

Sponsor type

University/education

Website

http://www.braininjuryoutcomes.com

Funders

Funder type

Government

Funder name

National Institute for Health Research (NIHR) (UK)

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes