Clinical Trial on Treatment of Intraventricular Hemorrhage (CLEAR IVH)

Johns Hopkins University

Status and phase: Completed; Phase 2

Conditions: Intraventricular Hemorrhage

Treatments: Drug: tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

Study type: Interventional

Funder types: Other; Industry; Other U.S. Federal agency

Identifiers

NCT00650858

ISRCTN47341677 (Registry Identifier)

IVH05

Details and patient eligibility

About

The specific objective of this trial is to determine the lowest dose and dose frequency possible with the best pharmacokinetic and safety profile and it's ability to remove a blood clot from the ventricular system.

Full description

The purpose of this trial is to determine the efficacy and pharmacokinetics of intraventricular injections of multiple low doses of rt-PA. Sixteen subjects were already randomized to receive intraventricular injections of with 0.3 mg or 1.0 mg of rt-PA every 12 hours for up to 8 doses. Results of this stage (n=16) were then analyzed and the most effective dose of 1.0 mg was chosen to be used in the second stage (n=36) to determine the optimal frequency of dosing. We propose to test if this intervention facilitates more rapid clot resolution, complete recovery function and decreased mortality from this condition.

Enrollment: 52 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18-75
2. IVC placed as standard of care using less than or equal to 2 complete passes.
3. Spontaneous ICH less than or equal to 30 cc.
4. Able to receive first dose within 48 hours of CT scan diagnosing IVH (providing the time of symptom onset to diagnostic CT does not exceed 12 hours).
5. Clot size measured on CT scan done 6 hours after IVC placement must be equal to the presentation clot size plus or minus 5 cc (as determined by the AxBxC)/2 method).
6. ON stability CT scan either the 3rd or 4th ventricles are occluded with blood (no evidence of CSF flow on CT).
7. SBP < 200 mmHg sustained for 6 hours.
8. Historical Rankin of 0 or 1.

Exclusion criteria

1. Suspected or untreated aneurysm or AVM (unless ruled out by angiogram or MRA/MRI).
2. Clotting disorders.
3. Patients with platelet count < 100,000, INR > 1.7, PT > 15s, or an elevated APTT.
4. Pregnancy (positive pregnancy test).
5. Infratentorial hemorrhage (i.e., parenchymal/posterior fossa hematoma; all cerebellar hematomas excluded).
6. SAH (An angiogram should be obtained when the diagnostic CT scan demonstrates subarachnoid hemorrhage or any hematoma location or appearance 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).
7. ICH enlargement during the 6-hour stabilization period (6 hour after IVC placement).
8. Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts.
9. Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention.
10. Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis.
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.
13. Participation in another simultaneous medical investigation or trial.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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52 participants in 3 patient groups

0.3 mg rt-PA

Active Comparator group

Description:

In stage 1 of the protocol, dose finding, subjects were randomized to either this 0.3 mg dose arm or the 1.0 mg dose arm. Subjects in this arm (0.3 mg) received up to 8 doses of 0.3 mg rt-PA every 12 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Treatment:

Drug: tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

1.0 mg rt-PA

Active Comparator group

Description:

In stage 1 of the protocol, dose finding, subjects were randomized to either this 1.0 mg dose arm or the 0.3 mg dose arm. Subjects in this arm (1.0 mg) received up to 8 doses of 1.0 mg rt-PA every 12 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Treatment:

Drug: tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

1.0 mg Rt-PA q8h

Experimental group

Description:

In stage 2 of the protocol, dose frequency, subjects received up to 8 doses of 1.0 mg of rt-PA (Cathflo) every 8 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Treatment:

Drug: tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)