Clinical trial NCT03300479: Clevidipine (Cleviprex®) Compared With Urapidil (Ebrantil®)
Official title: Clevidipine (Cleviprex®) Compared With Urapidil (Ebrantil®) for Blood Pressure Reduction in Patients With Primary Intracerebral Hemorrhage: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Nontraumatic Intracerebral Hemorrhage, Multiple Localized
Keywords: nontraumatic intracerebral hemorrhage
Cleviprex®
Ebrantil®
Systolic blood pressure
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2017-10-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After admission to the ICU the patients presenting with primary intracerebral hemorrhage are evaluated for enrollment. If systolic blood pressure is higher than 160 mmHg or \<160 mmHg under intravenous antihypertensive drug, started less than 3 h before randomizsation, the patient will be randomized in one of the two study groups and intravenous therapy with Cleviprex® or Ebrantil® will start immediately. Data of systemic haemodynamics will be collected continuously by online monitoring, starting at baseline and ending after 24h. 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 Cleviprex® or Ebrantil®, all patients receive Cardene® (standard care in daily clinical routine) for another 24h followed by orally administered antihypertensive medication.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Achieving the target systolic blood pressure
timeFrame: 1/2 hours
Secondary outcomes:
measure: Hypertensive burden - time
timeFrame: 24 hours
measure: Hypotensive burden - time
timeFrame: 24 hours
measure: Cumulative time out
timeFrame: 24 hours
measure: Blood pressure variability
timeFrame: 48 hours
measure: Hematoma growth
timeFrame: 6 hours
measure: Neurological state 1
timeFrame: 48 hours
measure: Neurological state 2
timeFrame: 48 hours
Other outcomes:
measure: Costs
timeFrame: 24 hours
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University of Zurich
name: Emanuela Keller, MD Prof
role: PRINCIPAL_INVESTIGATOR
References: