Clot lysis: evaluating accelerated resolution of intraventricular haemorrhage Phase III

Completed

• Conditions: Intraventricular haemorrhage (IVH) or IVH with intracerebral haemorrhage (ICH); Circulatory System; Intracerebral haemorrhage

• Registration Number: ISRCTN70157009
• Lead Sponsor: Individual Sponsor (USA)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-22
• Last Update Posted: 4 September 2017

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

1. Age 18-80.
2. Symptom onset < 24 hours prior to diagnostic CT scan.
3. Spontaneous Intracerebral haemorrhage (ICH) = to 30cc and IVH obstructing 3rd and/or 4th ventricles.
4. ICH clot stability: ICH must be = to 30cc on initial presentation and not exceed 35cc on subsequent pre-randomisation stability scans. A CT scan performed 6 hours or more after Intravenous catheter (IVC) placement must be stable (difference is less than or equal to 5 cc) compared to the most previous CT scan as determined by the (AxBxC)/2 method.
Temporary Criterion: If the clot is not stable (i.e., difference is greater than 5 cc), a repeat CT scan must be performed at least 6 hours later and compared to the most previous CT scan. Investigator may continue to screen every 2 hours up to 72 hours for the initial bleeding to stabilise, as long as the subject is able to receive drug administration within 72 hours of time of diagnostic CT scan and the clot remains less than or equal to 35 cc. If the size stabilises (i.e., enlargement less than or equal to 5 cc between 2 sequential CT scans) and remains less than or equal to 35 cc, the patient is eligible.
5. IVH clot stability: The width of the lateral ventricle most compromised by blood clot must not increase by more than 2 mm, allowing for movement of blood under influence of gravity.
Temporary Criterion: If the clot is not stable (i.e., difference is greater than 2 mm), a repeat CT scan must be performed at least 6 hours later and compared to the most previous CT scan. Investigator may continue to screen up to 72 hours for the initial bleeding to stabilise, as long as the subject is able to receive drug administration within 72 hours of time of diagnostic CT scan. If the size stabilises (i.e., enlargement less than or equal to 2 mm between 2 sequential CT scans), the patient is eligible.
6. Catheter tract bleeding must be less than or equal to 5cc on CT scan for stability.
Temporary Criterion: if a catheter tract haemorrhage is present on the CT scan done 6 hours after IVC placement and is greater than 5cc or greater than 5mm, obtain a repeat CT scan 12 hours later. If the catheter tract haemorrhage further enlarges by more than 5cc or more than 5mm as compared to the most previous CT scan, the investigator may continue to screen by repeat CT scan every 12 hours for the bleeding to stabilise, as long as the subject is able to receive drug administration within 72 hours of time of diagnostic CT scan. If the size stabilises (i.e., enlargement less than or equal to 5 cc or less than or equal to 5 mm between 2 sequential CT scans), the patient is eligible.
7. On stability CT scan, the 3rd and/or 4th ventricles are occluded with blood.
8. All patients randomised will have had EVD placed, ideally using no more than 2 complete passes (including soft passes using the original trajectory), on an emergent basis as defined by the standard of care neurosurgical/critical care decisions of the managing physicians. If more than 2 passes are required for placement, additional stabilisation of IVC site will be determined with a CT performed at 24 hours after IVC placement.
Temporary Criterion: If no IVC is in place at the time the patient is initially screened, the decision to place an IVC may occur after the patient is initially screened but an IVC must be in-place and stable at the time of randomisation.
9. Patients with primary IVH are eligible (i.e. with ICH=0).
10. Systolic Blood Pressure (SBP) < 200 mmHg sustai

Exclusion Criteria

1. Suspected (unless ruled out by angiogram or Magnetic Resonance Angiography/Imaging [MRA/MRI]) or untreated ruptured cerebral aneurysm, ruptured intracranial arteriovenous malformation (AVM), or tumour. Treatment of an existing aneurysm or AVM must have occurred at least 3 months before the current onset.
Temporary Criterion: This is especially important in primary IVH, when no ICH source is found. A CT angiogram, angiogram or MRA/MRI is sufficient to continue the screening process: if negative, the patient is eligible.
2. Presence of choroid plexus vascular malformation or Moyamoya disease.
3. Clotting disorders.
Temporary Criterion: Reversing anticoagulation will be permitted where long term anticoagulation is not required. Subjects requiring long term anticoagulation are excluded.
4. Platelet count < 100,000, International Normalized Ratio (INR) > 1.3, or an elevated activated Partial Thromboplastin Time (aPTT).
Temporary Criterion: Low platelet counts etc. can normalise, on admission, within 24 hours, an INR can also normalise to less than or equal to 1.3.
5. Pregnancy (positive serum or urine pregnancy test).
6. Infratentorial haemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy. Note: Patients with a posterior fossa ICH or cerebellar haematomas are ineligible.).
7. Subarachnoid Haemorrhage (SAH) at clinical presentation (an angiogram should be obtained when the diagnostic CT scan shows SAH or any haematoma location or appearance not strongly associated with hypertension. If the angiogram does not detect a bleeding source to account for the haemorrhage, the patient is eligible for the study.) Subsequent appearance of cortical SAH secondary to clot lysis is not a dosing endpoint.
Temporary Criterion: An angiogram can be obtained when the diagnostic CT scan demonstrates subarachnoid haemorrhage or any haematoma location suggestive of aneurysm or spearing not strongly associated with hypertension. If the angiogram does not demonstrate a bleeding source that accounts for the haemorrhage, the patient is eligible for the study.
8. ICH/IVH enlargement that cannot be stabilised in the treatment time window.
Temporary Criterion: ICH enlargement during the 6 hour stabilisation period (6 hours after IVC placement): It is permitted to screen up to 72 hours after diagnostic scan. If the ICH clot stabilises (i.e., enlarges no more than 5cc) and does not exceed 35cc (an ICH clot size of 35cc allows for stabilisation of a 5cc expansion for those patients at the upper limit of the ICH clot size limit), the patient is eligible.
9. Ongoing internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts. (Patients with prior bleeding that is clinically stable for 12 hours or more without any coagulopathy or bleeding disorder are eligible).
10. Multi-focal, superficial bleeding observed at a multiple vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention.
11. Prior enrollment in the study.
12. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
Temporary Criterion: Although these situations are often irreversible, under other conditions, change can occur over 24 hours.
13. Planned or simultaneous participation (between screening and Day 30) in another interventional

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Recovery of function, as defined as a modified Rankin Score of = 3, at 180 days post ictus