Perfusion and Antihypertensive Therapy in Acute Ischemic Stroke

NCT02327793 | Completed Phase 2

• 1 other identifier: PATIS Version 1.0
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to provide a description of blood flow changes in the brain after blood pressure lowering drugs are given. This information will be used by physicians to guide blood pressure lowering therapy in stroke patients in the future.

Conditions

Stroke, Acute

Keywords

Perfusion; Blood pressure

Outcome Measures

Primary Outcomes (1)

• Change in Volume of Hypoperfused Tissue

  Change in the volume of hypoperfused tissue, defined as that having a CBF \<19 ml/100g/min, between the acute and the post treatment initiation perfusion weighted scans.

  15-30 minutes

Secondary Outcomes (1)

• Time-to-Treatment

  15-30 minutes

Study Arms (3)

Mean Arterial Pressure <100 mmHg

NO INTERVENTION

Patients with mean arterial pressure \<100 mmHg at the time of the perfusion weighted magnetic resonance imaging will not be treated. After 15 minutes of the baseline perfusion imaging a repeat perfusion weighted magnetic resonance imaging would be performed.

Mean Arterial Pressure 100-120 mmHg

EXPERIMENTAL

Patients with mean arterial pressure between 100-120 mmHg at the time of the perfusion weighted magnetic resonance imaging will be treated with sublingual 0.3 mg nitroglycerin. A repeat blood pressure would be assessed at 5min, 10min, 15min and 20 min of nitroglycerin administration. After a sustained drop of blood pressure (\>10% of the baseline reading) as defined by two reading 5minutes apart, a perfusion weighted magnetic resonance imaging will be performed.

Drug: Nitroglycerin

Mean Arterial Pressure >120 mmHg

EXPERIMENTAL

Patients with mean arterial pressure \>120 mmHg at the time of the perfusion weighted magnetic resonance imaging will be treated with intravenous 10-20mg labetalol injection. A repeat blood pressure would be assessed at 5min, 10min, 15min and 20 min of labetalol injection. After a sustained drop in blood pressure (\>10% of the baseline reading) as defined by two reading 5minutes apart, a perfusion weighted magnetic resonance imaging will be performed.

Drug: Labetalol

Interventions

Nitroglycerin DRUG

Mean Arterial Pressure 100-120 mmHg

Labetalol DRUG

Mean Arterial Pressure >120 mmHg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute ischemic stroke within 72 hours of symptom onset. In cases where onset time can not be established, it will be considered to be the time when the patient was last known to be well.
• years or older.
• Patients with Partial Anterior Circulation Infarcts (PACI; Oxfordshire Stroke Classification Project; OSCP) will be included.
• Patients with Posterior Circulation Infarcts (POCI) will be included only if there is evidence of cortical infarction in the territory of the posterior cerebral artery or its branches, including the occipital and mesial temporal lobes.

You may not qualify if:

• Patients with a contraindication to the BP lowering protocol (i.e. known extracranial/intracranial arterial stenosis, high-grade stenotic valvular heart disease, or severe renal failure) will be ineligible, as will those with a definite indication for BP reduction (i.e. hypertensive encephalopathy, or aortic dissection).
• Patients with contraindications to MRI will be excluded, including metallic implants and any past sensitivity to gadolinium contrast media.
• Due to recent reports of nephrogenic systemic fibrosis associated with gadolinium exposure in individuals with pre-existing renal failure, patients with Creatinine \> 160 μmol/l or Glomerular Filtration Rate (GFR) \<60 ml/min will also be excluded.
• Patients with renal artery stenosis will be excluded from this study, irrespective of renal function.
• Due to the possibility that oxygen therapy may confound CBF measurements, patients requiring \>4 lpm to keep Sp02 ≥92% by nasal cannulae will be excluded.
• Patients with a suspected hemodynamic stroke mechanism will be ineligible. This will include patients with known or suspected hypotensive periods and/or a watershed territory of cerebral infarction seen on CT or MRI.
• Due to the possibility of increased susceptibility to BP reduction in patients with raised intracerebral pressure (ICP), those with evidence of significant mass effect secondary to acute infarction, including any degree of midline shift and/or ventricular compression will be ineligible. For the same reason, patients with head and eye deviation or other clinical evidence of a Total Anterior Circulation Infarct (TACI; OSCP) will also be ineligible.
• Due to technical difficulties associated with PWI in the posterior fossa, patients with brainstem and cerebellar strokes will be excluded.
• Patients with known sensitivity to nitroglycerin/labetalol/adhesives in nitroglycerin patches/ACE inhibitors/Angiotensin Receptor Blockers will be excluded.
• Amplification of the vasodilatory effects of topical nitroglycerin by phosphodiesterase inhibitors such as sildenafil or tadalafil can result in severe hypotension. Patients who have used either of these drugs within 12 h of initial assessment will therefore be excluded.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

MeSH Terms

Conditions

Stroke

Interventions

Nitroglycerin; Labetalol

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals; Ethanolamines; Amino Alcohols; Alcohols; Salicylamides; Amides; Amines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 24, 2014
• First Posted: December 30, 2014
• Study Start: June 1, 2009
• Primary Completion: July 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 26, 2017

Record last verified: 2017-10

Locations

CA (1)