Safety and Efficacy Study of Clevidipine to Control Hypertension in Patients Admitted With Aneurysmal Subarachnoid Hemorrhage

Phase 2

Terminated

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.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of SAH
Presence of unsecured aneurysm
Patient age between 18 and 80 years
Hunt and Hess grade <5 (non-sedated-paralyzed pt)
Glasgow Coma scale >4 (non-sedated-paralyzed pt)
BP above the pre-specified upper limit set by MD
Patient has not received pressors or inotropes
Patient has not received IV anti-hypertensives for more than 5 minutes (sodium nitroprusside infusion should be stopped as clevidipine is started
Patient has given informed consent

Exclusion Criteria

Patient is <18 or >80 years of age
Patient has Traumatic SAH
Patient has Perimesencephalic SAH
Hunt and Hess grade 5 (deeply comatose/ brain dead)
Glasgow Coma scale 3 or 4 (deeply comatose/brain dead)
Patient on pressors or anti-hypertensives for more than 5 minutes
SBP < 90 mm Hg
Heart rate >110
Patient with Left BBB
Patient with a permanent ventricular pacemaker
Known allergy to dihydropyridines or clevidipine
Known allergy to soy products, beans, eggs or egg products22. Patients with defective lipid metabolism or pathologic hyperlipidemia or lipid nephrosis
Acute pancreatitis, accompanied by hyperlipidemia
Severe aortic stenosis
Pregnancy

Arm && Interventions

Group	Intervention	Description
Clevidipine butyrate injectable emulsion	Clevidipine butyrate injectable emulsion	-

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures