Clot lysis: evaluating accelerated resolution of intraventricular hemorrhage Phase III - CLEAR III

• Conditions: Intraventricular haemorrhage; MedDRA version: 13.1Level: PTClassification code 10022840Term: Intraventricular haemorrhageSystem Organ Class: 10029205 - Nervous system disorders

• Registration Number: EUCTR2008-006916-39-HU
• Lead Sponsor: Johns Hopkins University (Prof. Daniel Daniel F. Hanley, MD)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10-18
• Last Update Posted: 26 June 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

1.Age 18-80.
2.Symptom onset less than 24 hrs prior to diagnostic CT scan.
3.Spontaneous ICH less than or equal to 30 cc and IVH obstructing 3rd and/or 4th ventricles.
4.ICH clot stability: ICH must be less than or equal to 30 cc on initial presentation and not exceed 35 cc on subsequent pre-randomization stability scans. A CT scan performed 6 hours or more after 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 > 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 12 hours up to 72 hours for the initial bleeding to stabilize, 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 stabilizes (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 > 2 mm, allowing for movement of blood under influence of gravity.
Temporary Criterion: If the clot is not stable (i.e., difference is > 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 stabilize, as long as the subject is able to receive drug administration within 72 hours of time of diagnostic CT scan. If the size stabilizes (i.e., enlargement less than or equal to 2mm between 2 sequential CT scans), the patient is eligible.
6.Catheter tract bleeding must be less than or equal to 5 cc on CT scan for stability.
Temporary criterion: If a catheter tract hemorrhage is present on the CT scan done 6 hours after IVC placement and is > 5 cc or > 5 mm, obtain a repeat CT scan 12 hours later. If the catheter tract hemorrhage further enlarges by > 5 cc or > 5 mm 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 stabilize, as long as the subject is able to receive drug administration within 72 hours of time of diagnostic CT scan. If the size stabilizes (i.e., enlargement less than or equal to 5 cc or less than or equal 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 randomized 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 stabilization 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 randomization.
9.Patients with primary IVH are eligible (i.e. with ICH=0).
10.SBP < 200 mmHg sustained for the 6 h before drug administration (closest to randomization).
Temporary criterion: Blood pressure

Exclusion Criteria

1.Suspected (unless ruled out by angiogram or MRA/MRI) or untreated ruptured cerebral aneurysm, ruptured intracranial AVM, or tumor. 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 a 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 anti-coagulation are excluded.
4.Platelet count < 100,000, INR > 1.3, or an elevated aPTT.
Temporary criterion: Low platelet counts etc. on admission can normalize within 24 hours as can an INR normalize to < 1.3.
5.Pregnancy (positive serum or urine pregnancy test).
6.Infratentorial hemorrhage (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 hematomas are ineligible.).
7.SAH at clinical presentation (an angiogram should be obtained when the diagnostic CT scan shows SAH or any hematoma location or appearance not strongly associated with hypertension. If the angiogram does not detect a bleeding source to account for the hemorrhage, 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 hemorrhage or any hematoma location suggestive of aneurysm or appearing not strongly associated with hypertension. If the angiogram does not demonstrate a bleeding source that accounts for the hemorrhage, the patient is eligible for the study.
8.ICH/IVH enlargement that cannot be stabilized in the treatment time window.
Temporary criterion: ICH enlargement during the 6-hour stabilization period (6 hours after IVC placement): It is permitted to screen up to 72 hours after diagnostic scan. If the ICH clot size stabilizes (i.e., enlarges no more than 5 cc) and does not exceed 35 cc (an ICH clot size of 35 cc allows for stabilization of a 5cc expansion for those patients at the upper limit of the ICH clot size limit), the patient is eligibile.
9.Ongoing internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts. (Patient with prior bleeding that is clinically stable for 12 h or more without any coagulopathy or bleeding disorder is eligible).
10.Multi-focal, superficial bleeding, observed at 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 medical investigation or clinical trial. Patients involved in observational, natural history, and/or epidemiological studies not involving an intervention are eligible.
14.No subject or legal r

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified