Nontraumatic Intracerebral Hemorrhage, Multiple LocalizedPhase 4ClevidipineNCT03300479
Clevidipine (Cleviprex®) Compared With Urapidil (Ebrantil®)
A Phase 4 study testing Clevidipine and Urapidil in people with Nontraumatic Intracerebral Hemorrhage, Multiple Localized, run by University of Zurich at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nontraumatic Intracerebral Hemorrhage, Multiple Localized
- What is being tested?
- Clevidipine and Urapidil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteSwitzerland
- Study dates
- 15 Jun 2017to 14 May 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clevidipine (Cleviprex®) Compared With Urapidil (Ebrantil®) for Blood Pressure Reduction in Patients With Primary Intracerebral Hemorrhage: A Randomized Controlled Trial
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.
Read the 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.
- Being tested
- Clevidipine, Urapidil
- Keywords
- nontraumatic intracerebral hemorrhage, Cleviprex®, Ebrantil®, Systolic blood pressure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClevidipineDrug
Also called Cleviprex®
Intravenous antihypertensive therapy with Clevidipine for the first 24 hours in patients with nontraumatic intracerebral hemorrhage (ICH).
UrapidilDrug
Also called Ebrantil®
We compare the therapy with Urapidil to Clevidipine for the acute phase (24 hours) in patients with ICH. We would like to show the efficacy and safety of Clevidipine in this special situation.
| Study group | Role | What they receive |
|---|---|---|
| Clevidipine | Experimental | 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). Receives: Drug: Clevidipine |
| Urapidil | Active comparator | 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). Receives: Drug: Urapidil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achieving the target systolic blood pressure
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®)
Measured: 1/2 hours
Secondary outcomes (7)
Hypertensive burden - time
- Hypertensive burden - time out of target range (SBP > 160 mmHg) multiplied with the numeric difference to 160mmHg
Measured: 24 hours
Hypotensive burden - time
- Hypotensive burden - time out of target range (SBP < 120 mmHg) multiplied with the numeric difference to 120mmHg
Measured: 24 hours
Cumulative time out
- Cumulative time out of target systolic blood pressure range (>160 or <120 mmHg)
Measured: 24 hours
Blood pressure variability
- Blood pressure variability (determined as Standard Deviation (SD) of SBP over time)
Measured: 48 hours
Hematoma growth
- Hematoma growth within 6 hours after admission (CCT scan)
Measured: 6 hours
Neurological state 1
- Glasgow Coma Scale (GCS)
Measured: 48 hours
Neurological state 2
- modified Ranking Scale (mRS)
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2017
- Study start15 Jun 2017
- Primary completion14 May 2021
- Study completion14 May 2021
Why it stopped: No patient enrolled. No study conduct due to lack of human resources.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nontraumatic Intracerebral Hemorrhage, Multiple LocalizedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Emanuela Keller, University of Zurich
- Investigators
- Emanuela Keller, MD Prof, Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03300479
- Sponsor's protocol ID
- 2017-00379
- Other IDs
- 2017
- Acronym
- Clevidipine
- Status last verified
- Nov 2021
- First submitted
- 8 Sep 2017
- Last updated
- 8 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clevidipine (Cleviprex®) Compared With Urapidil (Ebrantil®) for Blood Pressure Reduction in Patients With Primary Intracerebral Hemorrhage: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03300479
- Acronym / sponsor ID
- Clevidipine / 2017-00379
- Keywords
- nontraumatic intracerebral hemorrhage, Cleviprex®, Ebrantil®, Systolic blood pressure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No patient enrolled. No study conduct due to lack of human resources.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 15 Jun 2017 (actual)
- Primary completion
- 14 May 2021 (actual)
- Study completion
- 14 May 2021 (actual)
- First posted
- 3 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Clevidipine | Experimental | Drug: ClevidipineThe 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). |
| Urapidil | Active comparator | Drug: UrapidilThe 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClevidipineAlso: Cleviprex®Intravenous antihypertensive therapy with Clevidipine for the first 24 hours in patients with nontraumatic intracerebral hemorrhage (ICH). | Drug | Clevidipine |
| UrapidilAlso: Ebrantil®We compare the therapy with Urapidil to Clevidipine for the acute phase (24 hours) in patients with ICH. We would like to show the efficacy and safety of Clevidipine in this special situation. | Drug | Urapidil |
Primary outcome
Achieving the target systolic blood pressure
Time frame: 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®)
7 secondary outcomes
Hypertensive burden - time
Time frame: 24 hours
Hypotensive burden - time
Time frame: 24 hours
Cumulative time out
Time frame: 24 hours
Blood pressure variability
Time frame: 48 hours
Hematoma growth
Time frame: 6 hours
Neurological state 1
Time frame: 48 hours
Neurological state 2
Time frame: 48 hours
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2021.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emanuela Keller, MD Prof principal investigator
University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clevidipine and Urapidil in people with Nontraumatic Intracerebral Hemorrhage, Multiple Localized, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 8 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Achieving the target systolic blood pressure (time frame: 1/2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2021.