Clevidipine (Cleviprex®) Compared With Urapidil (Ebrantil®)
- Conditions
- Nontraumatic Intracerebral Hemorrhage, Multiple Localized
- Interventions
- Registration Number
- NCT03300479
- Lead Sponsor
- University of Zurich
- Brief Summary
Intracerebral hemorrhage (ICH) is responsible for 10-15% of primary strokes. ICH is a dynamic process with three phases: initial hemorrhage, followed by hematoma expansion and perihematoma edema formation. Hematoma volume is correlated with disease progression and outcome. Contemporary evidence proposes that elevated blood pressure is associated with hematoma expansion while more than 90% of patients with ICH present with acute hypertension. Uncontrolled blood pressure is a leading cause of ICH and it seems also to be a factor of poorer outcomes. Therefore, rapid reduction and control of blood pressure might ease disease progression and improve the outcome. Clevidipine (Cleviprex®), an ultrashort-acting dihydropyridine calcium channel antagonist, with its rapid onset and short duration might be more effective than conventional antihypertensives to achieve rapid blood pressure control in patients with acute ICH.
- Detailed Description
After admission to the ICU the patients presenting with primary intracerebral hemorrhage (ICH) are evaluated for enrollment. If systolic blood pressure (SBP) is higher than 160 mmHg or SBP \<160 mmHg under intravenous antihypertensive drug (e.g. Urapidil), started less than 3 h before randomization, the patient will be randomized in one of the two study groups and intravenous therapy with Clevidipine (Cleviprex®) or Urapidil (Ebrantil®) will start immediately. Data of systemic haemodynamics will be collected continuously by online monitoring, starting at baseline and ending after 24h (study data measurements). In particular, all blood pressure measurements are extracted via an arterial line, which is placed as standard of care in these patients. If the target values are not attained within 30 minutes, the investigators can add or switch to alternative antihypertensive drugs of their choice. 24h after initiation of Clevidipine (Cleviprex®) or Urapidil (Ebrantil®), all patients receive Nicardipine (Cardene®) (standard care in daily clinical routine) for another 24h followed by orally administered antihypertensive medication.
Intracerebral hematoma volume will be determined by readings of noncontrast brain computed tomography (CT) scans using the ABC/2 rule to calculate the volume. As a standard in these patients a CT scan is performed 6 hours after admission to the ICU.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Primary intracerebral hemorrhage (ICH)
- Systolic blood pressure (SBP) > 160 mmHg at screening
- Systolic blood pressure (SBP) <160 mmHg under intravenous antihypertensive drug (e.g. Urapidil), started less than 3 h before randomization
- 18 to unlimited years of age
- Signed informed consent obtained
- Patients with secondary hemorrhage (bleeding source as aneurysm, arteriovenous malformation or traumatic)
- Patients with concomitant severe critical illness (e.g. sepsis, multi-organ failure)
- Positive pregnancy test for any female of childbearing potential or breast feeding female
- Known allergy to any component of Clevidipine (Cleviprex®), Urapidil Ebrantil®), soya bean oil or severe egg protein allergy
- Contraindications for Clevidipine (Cleviprex®): defect in the lipid metabolism, critical aortic stenosis
- Contraindications for Urapidil (Ebrantil®): aortic coarctation, arterio-venous shunt, breastfeeding period
- Patients with pre-existing disability and legal representative
- Patients participating in a interventional clinical trial within the last 30 days before Start of Treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Urapidil Urapidil The treatment starts at admission to the ICU for 24 hours with 5 mg to a maximum of 40 mg Urapidil per hour infused intravenously and continuously to reach the systolic target pressure \< 160 mmHg (\>120 mmHg). Clevidipine Clevidipine The treatment starts at admission to the ICU for 24 hours with 2 mg to a maximum of 16 mg Clevidipine per hour infused intravenously and continuously to reach the systolic target pressure \< 160 mmHg (\>120 mmHg).
- Primary Outcome Measures
Name Time Method Achieving the target systolic blood pressure 1/2 hours Number of patients achieving the target systolic blood pressure (SBP) values (160 -120 mmHg) within 30 minutes after initiation of Clevidipine (Cleviprex®) or Urapidil (Ebrantil®)
- Secondary Outcome Measures
Name Time Method Blood pressure variability 48 hours • Blood pressure variability (determined as Standard Deviation (SD) of SBP over time)
Neurological state 1 48 hours • Glasgow Coma Scale (GCS)
Hypertensive burden - time 24 hours • Hypertensive burden - time out of target range (SBP \> 160 mmHg) multiplied with the numeric difference to 160mmHg
Hypotensive burden - time 24 hours • Hypotensive burden - time out of target range (SBP \< 120 mmHg) multiplied with the numeric difference to 120mmHg
Cumulative time out 24 hours • Cumulative time out of target systolic blood pressure range (\>160 or \<120 mmHg)
Hematoma growth 6 hours • Hematoma growth within 6 hours after admission (CCT scan)
Neurological state 2 48 hours • modified Ranking Scale (mRS)
Trial Locations
- Locations (1)
University Hospital Zurich
🇨🇭Zurich, Switzerland