Minimally invasive surgery plus rt-PA for ICH evacuation

ISRCTN	ISRCTN50142667
DOI	https://doi.org/10.1186/ISRCTN50142667
EudraCT/CTIS number	2007-006006-22
ClinicalTrials.gov number	NCT00224770
Secondary identifying numbers	6469

Submission date: 29/04/2010
Registration date: 29/04/2010
Last edited: 10/09/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Study website

Contact information

Dr Barbara Gregson
Scientific

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

Study information

Study design	Randomised interventional treatment trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Minimally invasive surgery plus rt-PA for ICH evacuation
Study acronym	MISTIE
Study hypothesis	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.
Ethics approval(s)	14/01/2009, ref: 08/H0906/158
Condition	Topic: Generic Health Relevance and Cross Cutting Themes, Stroke Research Network; Subtopic: Generic Health Relevance (all Subtopics); Disease: Surgery
Intervention	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) 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
Primary outcome measure	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 study start date	01/04/2010
Overall study end date	01/12/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 110
Total final enrolment	141
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 (ABC)/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 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

England
Germany
United Kingdom

Study participating centre

Neurosurgical Trials Unit

Newcastle upon Tyne
NE2 4AE
United Kingdom

Sponsor information

Johns Hopkins University (USA)
University/education

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

Website	http://www.braininjuryoutcomes.com
"ROR"	https://ror.org/00za53h95

Funders

Funder type

Government

National Institute for Health Research (NIHR) (UK)
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			10/09/2019	No	No
Results article	results	01/03/2013	10/09/2019	Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

10/09/2019: The following changes were made to the trial record:
1. Publication reference added.
2. ClinicalTrials.gov number added.
3. A link to basic results was added to basic results (scientific).
4. The total final enrolment was added.
15/03/2017: No publications found in PubMed, verifying study status with principal investigator