Clevidipine to control high blood pressure after acute intracerebral hemorrhage

Clevidipine for the Antihypertensive Treatment of Acute Intracerebral Hemorrhage

This trial will test whether IV clevidipine helps adults with acute intracerebral hemorrhage reach and keep their target systolic blood pressure within 60 minutes better than other IV blood-pressure medicines.

Quick facts

• Study type: Observational
• Enrollment: 1000 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Zeenat Qureshi Stroke Institute (Academic / other)
• Locations: 13 sites (Irvine, California and 12 other locations)
• Trial ID: NCT06402968 on ClinicalTrials.gov

What this trial studies

This observational study compares adults with acute intracerebral hemorrhage who receive IV clevidipine to those treated with alternate IV antihypertensive regimens. Eligible patients present within 12 hours of symptom onset, have a CT-confirmed intraparenchymal hematoma larger than 5 cc, and have systolic blood pressure between 150 and 219 mmHg on repeat measurements. The primary outcome is the proportion of patients who reach and maintain a predefined SBP target with stability within 60 minutes of enrollment. The study is conducted at multiple California sites including UC Irvine, Antelope Valley Medical Center, and Stanford Health Care.

Who should consider this trial

Good fit: Adults (18–99 years) with new neurological deficits from intracerebral hemorrhage presenting within 12 hours, an admission SBP of 150–219 mmHg, NIHSS ≥1, GCS ≥5, and a CT hematoma volume >5 cc are the intended participants.

Not a fit: Patients with very high blood pressure (SBP ≥220 mmHg), very small or microhemorrhages, presentation beyond 12 hours, or contraindications to the study medications are unlikely to benefit from this comparison.

Why it matters

Potential benefit: If successful, more rapid and stable blood-pressure control could reduce hematoma expansion and improve recovery after intracerebral hemorrhage.

How similar studies have performed: Large trials of intensive BP lowering in ICH (for example INTERACT2 and ATACH-2) showed mixed results, and while clevidipine is used in other acute settings it is less well studied specifically for ICH.

Eligibility criteria

Inclusion Criteria

1. Age 18 years or older and less than 100 years.
2. Onset of new neurological deficits within 12 hours at the time of enrollment and IV clevidipine or alternate IV antihypertensive regimen can be initiated within 12 hours of symptom onset.
3. Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
4. Initial National Institutes of Health Stroke Scale (NIHSS) score of 1 or greater.
5. Total GCS score (aggregate of verbal, eye, and motor response scores) of 5 or greater at enrollment
6. Computed Tomography (CT) scan of the brain demonstrates intraparenchymal hematoma with manual hematoma volume measurement \>5 cc (excluding microhemorrhages)
7. Admission SBP greater than and equal to 150 mmHg but less than 220 mmHg on two repeat measurements at least 5 minutes apart, but no more than 10 minutes apart. The reason for exclusion of ICH patients with initial SBP ≥220 mm Hg is based on a post hoc analysis of ATACH-2, which found that patients with initial SBP ≥220 mm Hg (22.8% of the cohort) reported higher rates of neurological deterioration at 24 hours and renal adverse events until day 7 or discharge in patients treated with intensive SBP reduction compared with standard SBP lowering, without any benefit in reducing hematoma expansion at 24 hours or death or severe disability at 90 days.
8. Signed and dated informed consent by subject, legally authorized representative, or surrogate before index hospital discharge for data collection and agreement to participate in 90- and 180-day follow-up visits.
9. Patients with anticoagulant-related ICH are eligible as long as anticoagulant reversal is concurrently undertaken consistent with AHA/ASA guidelines.
10. Patients who will undergo surgical evacuation consistent with AHA/ASA guidelines or local institutional guidelines are eligible unless surgical evacuation is being performed within 6 hours of initiation of IV clevidipine or alternate IV antihypertensive medication regimen. Ultra-early surgery will necessitate use of anesthetic agents which will confound the effect of IV clevidipine or alternate IV antihypertensive medication regimen. Ultra-early surgery/intervention was not used in the minimally invasive catheter evacuation followed by thrombolysis (MISTIE)/ Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) trials, which required ICH patients to undergo a repeat CT scan after 6 hours to document absence of any hematoma expansion (with ≤5 mL hematoma growth) compared to a previous CT scan prior to any surgical intervention.
11. Patients requiring external ventricular drainage consistent with AHA/ASA guidelines or local institutional guidelines are eligible.

Exclusion Criteria

1. Time of symptom onset cannot be reliably assessed.
2. Previously known neoplasms, arteriovenous malformation (AVM), or aneurysms.
3. Intracerebral hematoma considered to be related to trauma.
4. ICH located in infratentorial regions such as pons or midbrain (cerebellar ICH is not an exclusion criteria).
5. Subject considered a candidate for immediate surgical intervention by the neurosurgery service.
6. Pregnancy, parturition within previous 30 days, or active lactation.
7. Any history of bleeding diathesis or coagulopathy except anticoagulant related ICH.
8. Platelet count of less than 50,000/mm3.
9. Known sensitivity to nicardipine or clevidipine.
10. Patient's living will precludes aggressive ICU management.
11. Patients with allergies to soybeans, soy products, eggs, or egg products.
12. Defective lipid metabolism such as pathologic hyperlipemia, lipoid nephrosis, or acute pancreatitis if it is accompanied by hyperlipidemia.
13. Patients with severe aortic stenosis.

Where this trial is running

Irvine, California and 12 other locations

• University of California — Irvine, California, United States (Recruiting)
• Antelope Valley Medical Center — Lancaster, California, United States (Recruiting)
• Stanford Medical Center (Stanford Health Care) — Palo Alto, California, United States (Recruiting)
• Cleveland Clinic Martin North Hospital — Stuart, Florida, United States (Recruiting)
• University of South Florida — Tampa, Florida, United States (Recruiting)
• Augusta University-Neuroscience Center — Augusta, Georgia, United States (Recruiting)
• University of Michigan Health-West — Wyoming, Michigan, United States (Recruiting)
• University of Missouri — Columbia, Missouri, United States (Recruiting)
• Albany Medical Center — Albany, New York, United States (Recruiting)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)
• Cleveland Clinic Foundation — Cleveland, Ohio, United States (Recruiting)
• UT Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
• University of Texas Health Science Center San Antonio — San Antonio, Texas, United States (Recruiting)

Conditions Intracerebral Hemorrhage; Stroke; Hypertension