Clinical trial NCT05399550: Study to Evaluate The Safety and Efficacy of Balovaptan in Participants With Acute Ischemic Stroke at a High Risk of Developing Malignant Brain Edema
Official title: A Phase II, Randomized, Double Blind, Placebo Controlled Multicenter Study to Evaluate The Safety and Efficacy of Balovaptan in Patients With Acute Ischemic Stroke at High Risk of Developing Malignant Cerebral Edema
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-06-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the safety, efficacy, and pharmacokinetics of balovaptan compared with placebo in participants with acute ischemic stroke (AIS) at risk of developing Malignant Cerebral Edema (MCE)


Eligibility criteria: Inclusion Criteria:

* Diagnosis of LVO in the anterior circulation such that study drug administration can be initiated within 12 hours of LKW and at risk of MCE development, as defined as follows:
* Documented occlusion of terminus ICA and/or MCA on CTA or magnetic resonance angiogram and
* ASPECTS score \</=5 on NCCT and
* NIHSS \>15 for the non-dominant hemisphere and \>20 for the dominant hemisphere (or \> 20 if dominant/non-dominant hemisphere unknown)
* Present with a WUS \</=8 hours from awakening provided the above criteria are met
* Participants with a history of seizures on anti-epileptic medications may be included if they have been on stable doses of those medications for at least 12 weeks prior to LKW, they have not experienced seizures during that time frame, and their anti-epileptic medicines are continued during the study
* For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception and agree to refrain from donating eggs
* No specific contraception methods for males are required.

Exclusion Criteria:

* Participants who are \>12 hours from LKW at the start of treatment with study drug or \>8 hours from awakening with WUS
* Any MLS on brain imaging
* Evidence of intracranial hemorrhage at screening based on NCCT
* Contraindication to MRI examination
* Evidence of additional anterior cerebral artery (ACA) infarction
* Diagnosis of brain death
* Planned surgical decompression prior to randomization
* Participants with a known history of a hereditary bleeding disorder which increases bleeding risk
* Chronic kidney disease stage III or higher
* Hepatic injury
* Diagnosis of diabetes insipidus
* Participants who have received any prophylactic hyperosmolar therapy
* Participants who have received treatment with any other V1a and/or V2 receptor-blocking agent or glyburide
* A preexisting medical condition for which the participant is unlikely to survive the next 6 months
* Planned limitation or withdrawal of life-sustaining treatment during hospital admission
* Participants who are pregnant or breastfeeding, or intending to become pregnant

Primary outcomes:
measure: Amount of midline shift (MLS) at 72 hours from Last Known Well (LKW)
timeFrame: 72 Hours from Last Known Well
Secondary outcomes:
measure: Percentage of Participants with modified Rankin Scale-Structured Interview (mRS-SI) score </= 4 vs. >4
timeFrame: At Day 90
measure: Amount of MLS
timeFrame: At 48 hours and 96-120 hours from LKW
measure: Percentage of Participants with Surgical DHC Performed
timeFrame: From Baseline up to Day 90
measure: Percentage of Participants Who Received Hyperosmolar therapy following initiation of study treatment
timeFrame: From Baseline up to Day 90
measure: National Institute of Health Stroke Scale (NIHSS) score
timeFrame: At Day 4 and Day 90
measure: Mortality
timeFrame: At Day 30
measure: mRS-SI score
timeFrame: At Day 30
measure: Functional Independence Measure (FIM) score
timeFrame: At Discharge or Day 10 and Day 90
measure: Glasgow Outcome Scale Extended (GOSE) Score
timeFrame: at Discharge or Day 10, Day 30 and Day 90
measure: Stroke Impact Scale-16 (SIS-16) score
timeFrame: At Day 30 and Day 90
measure: Length (in days) of ICU and Hospital Stay
timeFrame: From Baseline to Day 90
measure: Number of participants with adverse events and severity of adverse events
timeFrame: From Baseline to Day 90
measure: Plasma concentrations of balovaptan at specified timepoints
timeFrame: From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)
measure: Area under the concentration-time curve from Time 0 to 24 hours after a given dose (AUC24hr)
timeFrame: From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]
measure: Maximum observed concentration (Cmax)
timeFrame: From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]
measure: Plasma drug concentration 24hours after the administration of a given dose (C24hr)
timeFrame: From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]
measure: Number of participants with safety findings on brain imaging
timeFrame: From Baseline to Day 90
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: CPMC Comprehensive Stroke Care Center
state: California
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: