Induced Hypertension for Acute Ischemic Stroke

• Status: Completed
• Trial end date: 2005-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The ultimate goal of this multicenter, phase II study is to increase blood pressure until either a neurologic response is seen or a target mean arterial pressure of 30% above baseline is achieved. IV fluids, IV phenylephrine and/or IV norepinephrine are used to rapidly raise mean arterial pressure in a controlled manner as serial assessments of neurologic function are performed.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University
• Collaborator: National Institutes of Health (NIH)
• Treatments: Midodrine; Norepinephrine; Oxymetazoline; Phenylephrine

Criteria

Inclusion Criteria:

• Patients with acute ischemic stroke in whom treatment can be initiated within 12 hours of a clearly defined symptom onset. (If the patient awakens with a deficit, time of onset is considered the time the patient was last seen functioning normally.)

• Age older then 18 years of age.

• Measurable neurologic deficit other than isolated facial weakness, sensory loss or ataxia. NIHSS must be > 4 points.

• Head CT showing no evidence of intracranial hemorrhage or mass lesion which might increase the risk of bleeding.

• Absence of ischemic changes on EKG (i.e. > than 1mm ST segment elevation or depression in at least two contiguous leads, new T waves inversion in two leads).

• No contraindication to MRI studies, including allergy to gadolinium.

Exclusion Criteria:

• History of unstable angina, any recent angina (defined as chest pain) in the past 3 months, recent myocardial infarction (less then 3 months), any history of ventricular arrhythmia, presence of left ventricular bundle branch block on EKG.

• History of severe and symptomatic cardiac valvular disease.

• History of congestive heart failure, dilated cardiomyopathy, hypertrophic obstructive cardiomyopathy, or known ejection fraction < 25%.

• Systolic blood pressure greater > 200 mm Hg or MAP > 120 mm HG when patient is initially monitored.

• Serum creatinine greater then 2 mg/dl.

• History of symptomatic peripheral vascular disease or Raynaud's syndrome.

• Suspected seizure at the onset of stroke.

• Treatment with IV tPA or other thrombolytic agent.

• Massive stroke (> 2/3 MCA territory) or any amount of midline shift due to cerebral edema on head CT.

• Pregnancy

• Current use of MAO inhibitors, tricyclic antidepressant medications, or cyclopropane or halothane anesthetic agents.

• Coma.

• Allergies or known contraindications to the use of IV phenylephrine, IV norepinephrine, sodium metabisulfite, or oral midodrine.

• Hemorrhage on initial MRI or CT or other structural lesion that might raise the risk of intracranial bleeding.

• Thrombocytopenia (plt < 100 k), PTT > 100 sec, INR > 3.0 at time of treatment.

• Participation in other investigational trial within 30 days.

• Moderate to severe baseline disability (pre-stroke Rankin score of > 3), severe or terminal concurrent medical illness with expected survival of < 3 months, or other concurrent medical or psychiatric condition which may limit neurologic assessment or patient follow-up in the opinion of the investigator.

• Requirement for anticoagulation with IV heparin or warfarin in the first 48 hours after enrollment.

• Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

• Toxicology screen positive for cocaine.

• Intubated at time of enrollment.

• Mesenteric or peripheral vascular thrombosis.

• Profound hypoxia or hypercarbia as defined as a PaO2 level less than 50 or a PaCO2 level of greater than 60.

• Norepinephrine Exclusion Criteria- The patient will not receive Norepinephrine if the patient has any of the following: lack of sufficient vascular access (central line or peripheral line greater than 18 gauge is sufficient), hypersensitivity to norepinephrine products, severe hypertension as in 4.2.4 above, tachycardia defined as HR >100 for 10 minutes sustained, myocardial infarction, pulmonary edema, peripheral ischemia, or ventricular arrhythmias.