Clinical Trial on Treatment of Intraventricular Hemorrhage "CLEAR IVH"

Completed

Phase 2 Results

Trial Description

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.

Detailed 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.

Conditions

Interventions

  • Tissue plasminogen activator (Activase┬«)Drug
    Other Names: Alteplase; tPA
    Intervention Desc: Thrombolytic
  • Tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo) Drug
    Other Names: rt-PA; Cathflo; Activase
    Intervention Desc: 0.3 mg and 1.0 mg of rt-PA (Cathflo) were administered every 12 hours (dose finding) and every 8 hours (dose frequency) via the intraventricular catheter to treat intraventricular hemorrhage.
    ARM 1: Kind: Experimental
    Label: 0.3 mg rt-PA
    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.
    ARM 2: Kind: Experimental
    Label: 1.0 mg rt-PA
    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.
    ARM 3: Kind: Experimental
    Label: 1.0 mg Rt-PA q8h
    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.

Trial Design

  • Allocation: Non-Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Single Group Assignment

Patient Involvement

During stage 1, subjects were randomized to receive either 0.3 mg or 1.0 mg of rt-PA every 12 hours for up to 8 doses. Subjects enrolled during stage 2 received 1.0 mg of rt-PA administered every 8 hours for up to 8 doses. After each injection the system was flushed with normal saline. The drainage system was then clamped closed for at least 1 hour before opening to spontaneous drainage at the level of the head until the next injection.

Outcomes

Type Measure Time Frame Safety Issue
Primary Safety endpoints: 30 day mortality, incidence of ventriculitis and meningitis, rate of bleeding events. Efficacy endpoints: rate of clot reduction at days 4-5 determined by CT scan
Secondary Rate of clot size reduction at Days 4-5 determined by CT scans (stages 1 and 2); 90 and 180 -day expanded Glasgow Outcome Scale, modified Rankin Scale, Barthel Index, Stroke Impact Scale (stage 2 only).
Primary 1.) 30-day mortality. 2.) Incidence of ventriculitis, meningitis. 3.) Rate of bleeding events. 180 days Yes
Secondary 1.) Rate of clot size reduction at Days 4-5 determined by CT scans (stages 1 and 2). 2.) 90 and 180 -day GOS< Rankin, Stroke Impact Scale (stage 2 only). 180 days Yes
Primary 30-day Mortality 30 days Yes
Primary Incidence of Bacterial Ventriculitis, Meningitis 30 days Yes
Primary Rate of Symptomatic Bleeding Events 30-days Yes
Secondary 1.) Rate of Clot Size Reduction at Days 4-5 Determined by CT Scans (Stages 1 and 2). 180 days Yes
Secondary 2.) 90 and 180 -Day GOS, Rankin, Stroke Impact Scale (Stage 2 Only). 90 and 180 days Yes

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