Antihypertensive Treatment in Acute Cerebral Hemorrhage

NCT00415610 | Completed Phase 1 Results DMC

• 2 other identifiers: 0609M93128R01NS044976-01A2
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this trial is to evaluate the safety and effectiveness of lowering blood pressure using nicardipine in persons with acute hypertension associated with intracerebral hemorrhage.

Conditions

Intracerebral Hemorrhage; Hypertension; Stroke

Keywords

cerebral hemorrhage; intracerebral hemorrhage; stroke; hypertension; blood pressure; nicardipine; antihypertensive agent; hematoma expansion

Outcome Measures

Primary Outcomes (3)

• Particpants Who Achieve and Maintain the Systolic Blood Pressure Goals for Each Treatment Tier.

  Feasibility of treatment was assessed by whether SBP reduction and maintenance within the respective target range was achieved (treatment success) or not (treatment failure), and secondarily by whether a significant difference between treatment arms was achieved. Treatment failure was defined based on the observed hourly hourly minimum SBP remaining greater than the upper limit of the target range for 2 consecutive hours after initiation of nicardipine infusion. Spontaneous decline of SBP below the lower limit of the specific tier was not considered treatment failure as all such declines were asymptomatic.The lower number in the more intensive treatment groups reflects in part the greater challenge of rapidly lowering systolic blood pressure to a more intensive (lower) range, as a higher number of treatment failures as pre-defined by meeting the SBP range goal within 3 hours of symptom onset in this group predictably occurred.

  Within 3 hours of symptom onset and sustained through 18-24 hours.

• Number of Participants With Neurological Deteriorations (Decrease of 2 or More Points on the GCS Score or an Increase of 4 or More Points on the NIHSS Score) During the 24 Hour Treatment",

  Neurological status was monitored quantitatively and independently of other adverse events using two scales. The Glasgow Coma Scale (GCS) score measures level of consciousness in eye, motor, and verbal components. At least one point is given in each category. The scale ranges from 3 to 15, with 3 indicating deep unconsciousness and 15 indicating consciousness is not impaired. The National Institutes of Health Stroke Scale (NIHSS) quantifies neurologic deficits in 11 categories. Level of consciousness, horizontal eye movements, visual fields, facial palsy, movement in each limb, sensation, language and speech, and extinction or inattention on one side of the body are tested. Scores range from 0 to 42; 0 indicates normal function and higher scores indicate greater deficit severity.

  within the first 72 hours of treatment initiation

• Total Number of Serious Adverse Events Within the Initial 72 Hours From Treatment Per Subject

  Serious adverse events were ascertained by site investigators using FDA-defined guidelines, defined as any untoward clinical events having been fatal, life-threatening, resulting in new or prolonged hospitalization, resulting in disability or congenital anomaly, or requiring intervention to prevent permanent impairment or damage. Subjects were followed closely from randomization through 90 days. The initial 72-hour period was chosen as the most meaningful time period for which to examine SAEs likely to be related to the acute safety of the study treatment.

  from treatment initiation through 72 hours

Secondary Outcomes (1)

• Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals

  3 months

Other Outcomes (1)

• Particpants Who Achieve Reduction of Blood Pressure and Maintain Treatment Goals (the Specified Systolic Blood Pressure Range for the 18-24 Hour Period) Without Neurological Deterioration or Side Effects Resulting in Death.

  From enrollment through 3 months

Study Arms (3)

Tier 1

OTHER

Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 170 to 200 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Drug: nicardipine

Tier 2

OTHER

Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 140 to 170 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Drug: nicardipine

Tier 3

OTHER

Dose escalation: The scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine to a range between 110 to 140 mmHg. Treatment with nicardipine must begin within 6 hours of symptom onset and will continue for an estimated 18 - 24 hours, until SBP is stabilized. The assigned SBP range will be maintained for 24 hours. After 24 hours, management of blood pressure is at the discretion of the primary physician.

Drug: nicardipine

Interventions

nicardipine DRUG

Intravenous (IV) nicardipine infusion. It is expected that the treatment duration will vary between 18 and 24 hours. * Started at 5mg/h * Titrated by 2.5mg/hour every 15 minutes to bring systolic blood pressure in target range for the applicable Tier. Max dose 15mg/hour \*Once target systolic blood pressure reached, dose decreased by 2.5mg/hour every 15 minutes until systolic blood pressure maintained in the target range or the medication is discontinued.

Also known as: Cardene, nicardipine hydrochloride

Tier 1; Tier 2; Tier 3

Eligibility Criteria

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

You may qualify if:

• Age older than 18 years.
• Onset of new neurological signs of a stroke within 12 hours of the time to evaluation AND initiation of treatment with intravenous nicardipine.
• Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
• The total GCS score is greater than 8 at the time of enrollment.
• CT scan demonstrates intraparenchymal hematoma with manual hematoma volume measurement less than 60 cc.
• ICH is supratentorial and is located in lobar, basal ganglionic, or thalamic based on the initial CT scan appearance.
• Admission systolic blood pressure greater than 170 mm Hg on two repeat measurements at least 5 minutes apart.
• Evidence of chronic hypertension.
• Subject is not considered a surgical candidate by the neurosurgery service.

You may not qualify if:

• Time of symptom onset cannot be reliably assessed.
• Previously known neoplasms, arteriovenous malformation, or aneurysms.
• Intracerebral hematoma considered to be related to trauma by the neurologist or neurosurgeon.
• ICH is located in the cortex or infratentorial regions such as pons or cerebellum.
• Blood is visualized in the subarachnoid space.
• Intravenous nicardipine cannot be initiated within 12 hours of symptom onset.
• Use of clonidine hydrochloride and other central alpha-agonist within the last 48 hours that have the potential of withdrawal hypertension.
• Pregnancy, lactation, or parturition within previous 30 days.
• Any history of bleeding diathesis or coagulopathy, including the use of warfarin.
• Use of heparin in the previous 48 hours and a prolonged partial thromboplastin time.
• Known atrial-ventricular heart block other than first degree, or sick sinus syndrome without a pacemaker.
• Intolerance to calcium channel blockers.
• Exposure to study medication in the preceding 24 hours prior to enrollment.
• A platelet counts less than 100 000/mm3.
• Major surgery within the previous six weeks.

Sponsors & Collaborators

• University of Minnesota: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (12)

University of Southern California

Los Angeles, California, 90033, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

The University of Kansas School of Medicine, Wichita Via Christi Regional Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General/Brigham Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Clinical Coordinating Center: University of Minnesota, Fairview Hospital

Minneapolis, Minnesota, 55455, United States

Location

Saint Louis University

St Louis, Missouri, 63108, United States

Location

JFK Medical Center

Edison, New Jersey, 08818, United States

Location

University of Medicine and Dentistry of New Jersey

Newark, New Jersey, 07107, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Statistical Coordinating Center: Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (7)

• Qureshi AI. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): rationale and design. Neurocrit Care. 2007;6(1):56-66. doi: 10.1385/ncc:6:1:56.

  PMID: 17356194 BACKGROUND

• Qureshi AI, Palesch YY, Martin R, Novitzke J, Cruz-Flores S, Ehtisham A, Ezzeddine MA, Goldstein JN, Hussein HM, Suri MF, Tariq N; Antihypertensive Treatment of Acute Cerebral Hemorrhage Study Investigators. Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study. Arch Neurol. 2010 May;67(5):570-6. doi: 10.1001/archneurol.2010.61.

  PMID: 20457956 RESULT

• Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) investigators. Antihypertensive treatment of acute cerebral hemorrhage. Crit Care Med. 2010 Feb;38(2):637-48. doi: 10.1097/CCM.0b013e3181b9e1a5.

  PMID: 19770736 RESULT

• Qureshi AI. Acute hypertensive response in patients with stroke: pathophysiology and management. Circulation. 2008 Jul 8;118(2):176-87. doi: 10.1161/CIRCULATIONAHA.107.723874. No abstract available.

  PMID: 18606927 RESULT

• Qureshi AI, Palesch YY, Martin R, Novitzke J, Cruz Flores S, Ehtisham A, Goldstein JN, Kirmani JF, Hussein HM, Suri MF, Tariq N; Antihypertensive Treatment of Acute Cerebral Hemorrhage Investigators. Systolic blood pressure reduction and risk of acute renal injury in patients with intracerebral hemorrhage. Am J Med. 2012 Jul;125(7):718.e1-6. doi: 10.1016/j.amjmed.2011.09.031. Epub 2012 May 4.

  PMID: 22560810 RESULT

• Qureshi AI, Palesch YY. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: design, methods, and rationale. Neurocrit Care. 2011 Dec;15(3):559-76. doi: 10.1007/s12028-011-9538-3.

  PMID: 21626077 RESULT

• Hussein HM, Tariq NA, Palesch YY, Qureshi AI; ATACH Investigators. Reliability of hematoma volume measurement at local sites in a multicenter acute intracerebral hemorrhage clinical trial. Stroke. 2013 Jan;44(1):237-9. doi: 10.1161/STROKEAHA.112.667220. Epub 2012 Dec 11.

  PMID: 23233387 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Hypertension; Stroke

Interventions

Nicardipine

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Limited by small sample size and likelihood of imbalances in subject characteristics among the three tiers. Clinical measures may be insensitive. Not designed to provide comparative event rates and not powered toward prediction of clinical outcomes.

Results Point of Contact

• Title: Adnan I Qureshi, MD
• Organization: University of Minnesota

qureshai@gmail.com

612-624-2431

Study Officials

• Adnan I. Qureshi, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open treatment assignment was employed because it is not safe to conceal SBP measurement. Patient data routinely entered by clinical staff were used to evaluate safety.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Staged intensity levels of rapid intravenous antihypertensive control for elevated SBP in patients with intracerebral hemorrhage were implemented in 3 sequential treatment arms to assess the feasibility and tolerability (safety) of this treatment.

Study Record Dates

• First Submitted: December 21, 2006
• First Posted: December 25, 2006
• Study Start: July 1, 2005
• Primary Completion: September 1, 2007
• Study Completion: March 1, 2008
• Last Updated: November 21, 2017
• Results First Posted: September 7, 2015

Record last verified: 2017-11

Locations

US (12)