Clinical Trial: Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage- A Safety and Tolerability Study

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage- A Safety and Tolerability Study

Brief 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.

Detailed Summary:

This is a single-center, open-label, safety and tolerability study. Based on findings in the literature from both animal research and clinical observations with ICH (intracerebral hemorrhage) associated with TBI (traumatic brain injury), this study will begin to look at the safety, tolerability, as well as potential effectiveness, of conivaptan to reduce CE (cerebral edema) in patients with non-traumatic ICH.

The seven patients in this study will receive 40mg/day of the study medication conivaptan. In this early phase study, our focus will be to assess the safety and tolerability of this medication. The available clinical data on conivaptan in the neurocritical care population suggest the potential harm is negligible. Data in TBI patients demonstrate conivaptan is safe and well tolerated using a single dose (20mg) to increase Na+ in a controlled fashion to reduce ICP. Previous work has demonstrated the safety and tolerability of conivaptan, in doses ranging from 20-80mg/day, in the neurocritical care population. Conivaptan has been demonstrated to be safe and effective in lowering ICP, and increasing serum sodium, in the neurocritical care population. Also noted have been improvements in cerebral perfusion pressure (CPP) and stable blood pressure, and a prolonged reduction in ICP. Finally, the method of intermittent bolus dosing of conivaptan is equally effective in raising and maintaining serum sodium in the neurocritical care population as continuous infusion, with potentially less risk of adverse reactions including phlebitis.

Conivaptan, a non-selective Arginine-Vasopressin (AVP) V1A/V2 antagonist that reduces aquaporin 4 production and promotes aquaresis, is approved for the treatment of euvolemic and hypervolemic hyponatremia. The exact cause of the observed reduction in ICP with conivaptan is uncertain. However, the
Sponsor: Jesse Corry

Current Primary Outcome: Patient tolerance of conivaptan [ Time Frame: Baseline to 168 hours post-enrollment ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• In-hospital mortality [ Time Frame: Enrollment through hospital discharge, up to 3 weeks ]
• Reduction in cerebral edema [ Time Frame: Baseline to 168 hours post-enrollment ]
  Reduction in cerebral edema (CE) as measured on CT. Goal is a 5-10% reduction in CE over time. Reduction will be measured both as absolute reduction, and as relative reduction, comparing the ratio of intracerebral hemorrhage ICH to edema volume. The absolute edema reduction is more clinically relevant, while the ratio of ICH to edema volume has more research relevance, to aid in designing the next related studies.
• Cost [ Time Frame: Enrollment through hospital discharge, up to 3 weeks ]
  Cost as measured by length of stay in the neuro ICU.
• Cost [ Time Frame: Baseline to 168 hours post-enrollment ]

  Cost as measured by:

  1. Need for external ventricular drain (EVD)/bolt or surgical procedures (craniectomy, clot evacuation,VPS) for reduction/management of CE.
  2. Need for central venous lines, arterial lines, peripherally inserted central venous catheter (PICC) lines, tracheostomy/percutaneous endoscopic gastrostomies (PEGs).
  3. Duration on ventilator.
  4. Duration of EVD/bolt.
• Modified Rankin Scale (mRS) score [ Time Frame: At discharge from ICU and from hospital, up to 3 weeks ]
  mRS stratified by APACHE II, GCS, and ICH Score

Original Secondary Outcome:

• In-hospital mortality [ Time Frame: Enrollment through hospital discharge, up to 3 weeks ]
• Reduction in cerebral edema [ Time Frame: Baseline to 168 hours post-enrollment ]
  Reduction in CE as measured on CT. Goal is a 5-10% reduction in CE over time. Reduction will be measured both as absolute reduction, and as relative reduction, comparing the ratio of ICH to edema volume. The absolute edema reduction is more clinically relevant, while the ratio of ICH to edema volume has more research relevance, to aid in designing the next related studies.
• Cost [ Time Frame: Enrollment through hospital discharge, up to 3 weeks ]
  Cost as measured by length of stay in the neuro ICU.
• Cost [ Time Frame: Baseline to 168 hours post-enrollment ]

  Cost as measured by:

  1. Need for EVD/bolt or surgical procedures (craniectomy, clot evacuation,VPS) for reduction/management of CE.
  2. Need for central venous lines, arterial lines, PICC lines, tracheostomy/PEGs.
  3. Duration on ventilator.
  4. Duration of EVD/bolt.
• Modified Rankin Scale (mRS) score [ Time Frame: At discharge from ICU and from hospital, up to 3 weeks ]
  mRS stratified by APACHE II, GCS, and ICH Score

Dates:
Date Received: December 14, 2016
Date Started: January 2017
Date Completion: January 2020
Last Updated: April 4, 2017
Last Verified: April 2017