Hypertension, Subarachnoid Hemorrhage
Conditions
Keywords
Subarachnoid hemorrhage, Hypertension, brain Aneurysm, intracerebral hemorrhage, antihypertensive, calcium channel blockers, infusion, neurocritical care
Brief summary
This study is designed to assess how rapidly and how safely Clevidipine can be used to control high Blood Pressure in patients with subarachnoid hemorrhage which is a type of brain bleed that happens because of a weak balloon like structure in one of the brain vessels. Control of blood pressure is of high value in preventing this balloon that ruptured and bled from rebleeding. The ultimate cure would be to shut down the aneurysm by a surgical procedure. Clevidipine is a drug that can lower blood pressure and it is given through the vein as a continuous infusion. It is a very short acting drug which is important in controlling labile blood pressure condition with rapid changes between up and down. This trial will test for its rapid actions and check for any side effects and possibly any other potential benefit.
Detailed description
This is a single center, single-arm, non-blinded dose titration efficacy and safety trial evaluating the ability of clevidipine, a vascular-selective L-type calcium channel antagonist, to rapidly control acute hypertension in patients with aneurysmal subarachnoid hemorrhage. At screening a clinical and neurological examination will be carried out. For the purposes of this study, acute hypertension will be defined as a range of SBP to be controlled within immediately prior to initiation of study drug. Approximately 20 patients with acute A SAH will be enrolled. Infusion of study drug will be initiated as soon ass the patient arrives in the ER and diagnosis is made and consent is obtained. All eligible patients will be enrolled to receive clevidipine in an open label manner. Clevidipine will be infused at an initial rate of 2.0 mg/h for the first 90 seconds. Thereafter, titration to higher infusion rates can be attempted as needed q90 seconds to obtain the target SBP range. Titration to effect is to proceed by doubling the dose every 90 seconds, up to a maximum of 32.0 mg/h, until the desired effect (SBP within the target range) is attained. Clevidipine infusion may continue for up to a maximum of 48 hours. Blood pressure and ICP recording will be recorded q 5 minutes. Assessment of safety will be performed throughout the treatment period and until 6 hours after termination of study drug.
Interventions
Clevidipine butyrate injectable emulsion infusion starting at 2 mg/hour and titrating up for effect till 32 mg/h for up to 24 hours starting in the emergency department and continued in the critical care units.
Sponsors
The Medicines Company
Henry Ford Health System
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of SAH 2. Presence of unsecured aneurysm 3. Patient age between 18 and 80 years 4. Hunt and Hess grade \<5 (non-sedated-paralyzed pt) 5. Glasgow Coma scale \>4 (non-sedated-paralyzed pt) 6. BP above the pre-specified upper limit set by MD 7. Patient has not received pressors or inotropes 8. Patient has not received IV anti-hypertensives for more than 5 minutes (sodium nitroprusside infusion should be stopped as clevidipine is started 9. Patient has given informed consent
Exclusion criteria
1. Patient is \<18 or \>80 years of age 2. Patient has Traumatic SAH 3. Patient has Perimesencephalic SAH 4. Hunt and Hess grade 5 (deeply comatose/ brain dead) 5. Glasgow Coma scale 3 or 4 (deeply comatose/brain dead) 6. Patient on pressors or anti-hypertensives for more than 5 minutes 7. SBP \< 90 mm Hg 8. Heart rate \>110 9. Patient with Left BBB 10. Patient with a permanent ventricular pacemaker 11. Known allergy to dihydropyridines or clevidipine 12. Known allergy to soy products, beans, eggs or egg products22. Patients with defective lipid metabolism or pathologic hyperlipidemia or lipid nephrosis 13. Acute pancreatitis, accompanied by hyperlipidemia 14. Severe aortic stenosis 15. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ability to Control and Maintain Blood Pressure Within a Certain Range by the Drug Infusion. | 30 minutes | All patients reached the SBP target after initiation of the first infusion within 14.2 ± 6.4 min (n = 5, range 7-22 min) Study closed October 2012 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clevidipine Butyrate Injectable Emulsion Clevidipine butyrate injectable emulsion: Clevidipine butyrate injectable emulsion infusion starting at 2 mg/hour and titrating up for effect till 32 mg/h for up to 24 hours starting in the emergency department and continued in the critical care units. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Clevidipine Butyrate Injectable Emulsion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 56.8 years STANDARD_DEVIATION 8.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 5 participants |
| SBP | 146.4 mmHg STANDARD_DEVIATION 2.48 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Ability to Control and Maintain Blood Pressure Within a Certain Range by the Drug Infusion.
All patients reached the SBP target after initiation of the first infusion within 14.2 ± 6.4 min (n = 5, range 7-22 min) Study closed October 2012
Time frame: 30 minutes
Population: 5 pts received clevidipine
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | Ability to Control and Maintain Blood Pressure Within a Certain Range by the Drug Infusion. | 14.2 min | Standard Deviation 6.4 |