E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute hypertension in patients who present with intracerebral hemorrhage |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022754 |
E.1.2 | Term | Intracerebral hemorrhage |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of a titration dosing regimen of an intravenous infusion of clevidipine for the treatment of acute hypertension in patients with intracerebral hemorrhage |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study include evaluating the percentage of patients who reach the target SBP within 30 minutes of the initiation of clevidipine infusion and percent change from baseline in SBP. Blood pressure management, the magnitude, frequency and duration of SBP excursion outside the target range and the percent time blood pressures were maintained within the target range during clevidipine infusion will be determined. The need for an alternative antihypertensive agent to maintain BP within the target range and the mean and median dose of clevidipine during the treatment period will be evaluated. The safety of a prolonged infusion of clevidipine based on clinical and laboratory assessments and AEs will be evaluated. Several exploratory analyses are planned which include evaluating the change in hematoma volumes, measuring perihematoma edema, assessment of neurological function following clevidipine infusion and explore BP control using wider ranges. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. CT evidence of intracerebral hemorrhage (diagnosis within 6 hours of symptom onset) 2. Age 18 years or older 3. Baseline systolic blood pressure (SBP) (immediately prior initiation of clevidipine) > 160 mm Hg measured using an arterial line 4. Requires antihypertensive therapy to achieve SBP less than or equal to 160 mm HG 5. Written informed consent from the patient or their legal representative before initiation of any study-related procedures |
|
E.4 | Principal exclusion criteria |
1. Decision for early surgical evacuation (e.g. large cerebellar or lobar hemorrhage) 2. Receipt of an oral hypertensive within 2 hours prior to initiation of clevidipine 3. Treatment with a continuous infusion of an intravenous (IV) antihypertensive agent prior to initiation of clevidipine. Bolus treatment with labetalol or hydralazine is permitted 4. Intracerebral hematoma considered to be related to trauma by neurologist or neurosurgeon 5. Aneurysmal sub-arachnoid hemorrhage 6. Glasgow coma score < 5 and fixed dilated pupils 7. Expectation that the patient will not tolerate or require intravenous antihypertensive therapy for a minimum of 30 minutes 8. Coagulopathy (INR >1.3 at screening) 9. Known or suspected aortic dissection 10. Acute myocardial infarction (AMI) 11. Positive pregnancy test or known pregnancy 12. Intolerance or allergy to calcium channel blockers 13. Allergy to soybean oil or egg lecithin 14. Known liver failure, cirrhosis or pancreatitis 15. Prior directives against advanced life support 16. Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The median time to achieve the target blood pressure (Systolic Blood Pressure less than or equal to 160 mm Hg to greater than or equal to 140 mmHg) within 30 minutes of initiation of the clevidipine infusion. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial is defined by the last visit of the last subject, which occurs 7 to 12 days following cessation of clevidipine infusion. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |