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

NCT03000283 | Completed Phase 1 Results FDA Drug

• 1 other identifier: NSJC-1601
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebral Hemorrhage; Cerebral Edema; Intracerebral Hemorrhage; Stroke

Keywords

Conivaptan

Outcome Measures

Primary Outcomes (1)

• Patient Tolerance of Conivaptan

  The number of participants with abnormal seizure activity and/or abnormal lab values and/or increase in infection rate and/or any drug-related adverse events.

  Baseline to 168 hours post-enrollment

Secondary Outcomes (5)

• In-hospital Mortality

  Enrollment through hospital discharge, up to 3 weeks

• Change in Cerebral Edema

  Baseline to 168 hours post-enrollment

• Cost

  Enrollment through hospital discharge, up to 3 weeks

• Cost

  Baseline to 168 hours post-enrollment

• Modified Rankin Scale (mRS) Score

  At discharge from ICU and from hospital, up to 3 weeks

Study Arms (1)

Conivaptan Treatment Group

EXPERIMENTAL

All seven patients in this arm will receive conivaptan as described in Interventions.

Drug: Conivaptan

Interventions

Conivaptan DRUG

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.

Also known as: Vaprisol

Conivaptan Treatment Group

Eligibility Criteria

• Age: 19 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years old and \< 80 years.
• Diagnosis of primary ICH \> 20 cc in volume.
• Enrollment within 48 hours from initial symptoms.
• 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.

You may not qualify if:

• Current need for renal replacement therapy (RRT).
• Glomerular filtration rate (GFR) of \<30 mL/minute at time of admission.
• Participation in another study for ICH or intraventricular hemorrhage.
• ICH related to infection, thrombolysis, subarachnoid hemorrhage, trauma or tumor.
• Presence of HIV or active fungal infection that is known based on information in the electronic medical record (EMR).
• Continued use of digoxin or amlodipine (as recommended by the manufacturer due to cytochrome P450 3A4 "CYP3A" inhibition).
• 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).
• Serum Na+\> 145 mmol/L (admission labs or any time prior to recruitment/enrollment).
• Unable to receive conivaptan based on contraindications indicated by the manufacturer.
• Pregnant or lactating females.
• Not expected to survive within 48 hours of admission, or a presumed diagnosis of brain death.

Sponsors & Collaborators

• Jesse Corry: lead

Study Sites (1)

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

Related Publications (52)

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  PMID: 32253717 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Brain Edema; Stroke

Interventions

conivaptan

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Jesse Corry
• Organization: Allina Health

Jesse.Corry@allina.com

651-241-6550

Study Officials

• Jesse J Corry, MD

  Allina Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: December 22, 2016
• Study Start: March 22, 2017
• Primary Completion: February 12, 2019
• Study Completion: April 15, 2019
• Last Updated: April 17, 2020
• Results First Posted: April 17, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)