Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage- A Safety and Tolerability Study
Condition: Cerebral Hemorrhage; Cerebral Edema; Intracerebral Hemorrhage; Stroke
MeSH terms: Cerebral Hemorrhage; Brain Edema; Hemorrhage; Edema
Intervention: Conivaptan
Intervention description: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen.
The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.
Intervention MeSH terms: Conivaptan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 19 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Conivaptan

Summary:

      The goal of this study is to preliminarily determine/estimate feasibility and whether
      frequent and early conivaptan use, at a dose currently determined to be safe (i.e.,
      40mg/day), is safe and well-tolerated in patients with cerebral edema from intracerebral
      hemorrhage (ICH) and pressure (ICP). A further goal is to preliminarily estimate whether
      conivaptan at this same dose can reduce cerebral edema (CE) in these same patients. This
      study is also an essential first step in understanding the role of conivaptan in CE
      management.

      Hypothesis: The frequent and early use of conivaptan at 40mg/day will be safe and
      well-tolerated, and also reduce cerebral edema, in patients with intracerebral hemorrhage and
      pressure.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age >18 years old and < 80 years.

          2. Diagnosis of primary ICH > 20 cc in volume.

          3. Enrollment within 48 hours from initial symptoms.

          4. Signed informed consent from the patient or obtained via their legally authorized
             representative (if the patient is not able to sign the informed consent themselves).
             The patient's decisional capacity to either provide or refuse consent will be
             determined using the Glasgow Coma Scale (GCS), which is being assessed at baseline and
             at 24 hours (+/-6hrs) after enrollment. A potential study participant with a GCS > 14
             will be asked to provide their own initial study consent. A GCS ≤ 14 would indicate
             the need to pursue consent via legally authorized representative.

        Exclusion Criteria:

          1. Current need for renal replacement therapy (RRT).

          2. Glomerular filtration rate (GFR) of <30 mL/minute at time of admission.

          3. Participation in another study for ICH or intraventricular hemorrhage.

          4. ICH related to infection, thrombolysis, subarachnoid hemorrhage, trauma or tumor.

          5. Presence of HIV or active fungal infection that is known based on information in the
             electronic medical record (EMR).

          6. Continued use of digoxin or amlodipine (as recommended by the manufacturer due to
             cytochrome P450 3A4 "CYP3A" inhibition).

          7. Active hepatic failure as defined by aspartate aminotransferase (AST) >160 units/L
             and/or alanine transaminase (ALT) >180 units/L, or total bilirubin levels greater than
             four times normal levels (>4.8mg/dL).

          8. Serum Na+> 145 mmol/L (admission labs or any time prior to recruitment/enrollment).

          9. Unable to receive conivaptan based on contraindications indicated by the manufacturer.

         10. Pregnant or lactating females.

         11. Not expected to survive within 48 hours of admission, or a presumed diagnosis of brain
             death.