Antihypertensive Treatment in Acute Cerebral Hemorrhage

Stroke Clinical Trial

— ATACH  

Official title:

Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00415610
• Other study ID #: 0609M93128
• Secondary ID: R01NS044976-01A2
• Status: Completed
• Phase: Phase 1
• First received: December 21, 2006
• Last updated: November 17, 2017
• Start date: July 2005
• Est. completion date: March 2008

Study information

• Verified date: November 2017
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

An estimated 37,000 to 52,400 people in the United States have intracerebral hemorrhage (ICH) every year. ICH——a form of stroke that has poor outcome and is difficult to treat——is associated with the highest mortality rate of all strokes. Hematoma expansion has been identified as the most common cause of neurological deterioration in persons with ICH. Early evidence suggests that acute hypertension (HTN)—or elevated blood pressure—may make some individuals more susceptible to hematoma expansion. Treating HTN acutely may prevent hematoma expansion, however, the effect of aggressive HTN treatment has not been determined.

The purpose of this trial is to evaluate the treatment feasibility and safety of lowering blood pressure using nicardipine——an antihypertensive medication——in persons who have acute HTN associated with ICH.

This pilot study will enroll 60 individuals who qualify with a presenting systolic blood pressure of at least 170 mmHg, have an ICH, and can be evaluated and treatment initiated within 6 hours of onset of stroke symptoms. In a stepwise fashion, the scientists will investigate the potential consequences of controlling blood pressure with intravenous nicardipine at 3 sequential levels: 170 to 200 mmHg, 140 to 170 mmHg, and 110 to 140 mmHg. Twenty participants will be enrolled per level.

Treatment will last 18 to 24 hours. Participants will stay in the hospital for about 7 days (including 24 hours in the intensive care unit for close monitoring) and will return for 1-hour follow-up visits at 30 days and at 90 days after discharge from the hospital. During these visits participants will receive neurological assessments to determine their functional outcome. For participants, the study will be completed after the 90-day follow-up visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 2008
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• History of any intracranial hemorrhage (including intracerebral or subarachnoid hemorrhage) or hemorrhagic stroke.

• Seizure at onset of stroke.

• Blood glucose less than 50 mg/dL or greater than 400 mg/dL.

• Current participation in another research drug treatment protocol.

• Isolated ventricular blood on CT scan.

• Subject has a living will that precludes aggressive intensive care unit management.

• Subject has acute myocardial infarction or renal failure that precludes use of aggressive antihypertensive therapy.

• Subjects with unstable angina or acute myocardial infarction within 2 weeks prior to ICH.

• Subjects with renal insufficiency with serum creatinine greater than 2.0 mg/dl or on renal dialysis.

• Sinus tachycardia exceeding 120 beats per minute or supraventricular tachycardia is observed during initial evaluation.

• Ischemic stroke within 4 weeks of presentation.

• Congestive heart failure graded as class III and IV by New York Heart Association (NYHA) classification.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Hypertension
• Intracerebral Hemorrhage
• Stroke

Intervention

Drug:
• nicardipine
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.

Locations

Country	Name	City	State
United States	Massachusetts General/Brigham Women's Hospital	Boston	Massachusetts
United States	Statistical Coordinating Center: Medical University of South Carolina	Charleston	South Carolina
United States	Case Western Reserve University	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	JFK Medical Center	Edison	New Jersey
United States	Kansas University Medical Center	Kansas City	Kansas
United States	The University of Kansas School of Medicine, Wichita Via Christi Regional Medical Center	Kansas City	Kansas
United States	University of Southern California	Los Angeles	California
United States	Clinical Coordinating Center: University of Minnesota, Fairview Hospital	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	Saint Louis University	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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 ren — View Citation

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 — View Citation

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. — View Citation

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. Review. — View Citation

Qureshi AI. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH): rationale and design. Neurocrit Care. 2007;6(1):56-66. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	The tolerability of the study treatment was further ascertained by examination of in-hospital, 1-month, or 3-month mortality in each treatment group.; This pilot study was not powered (did not plan to enroll an adequate number of patients) to draw meaningful conclusions about individual adverse event categories, outcome measures, or to make comparisons between the treatment arms beyond the overall feasibility and tolerability of rapidly and significantly lowering SBP following intracerebral hemorrhage.; The timing and magnitude of SBP reduction was also compared to the timing of individual safety events to further evaluate possible relationships between the study treatment, adverse events, and any recognizable safety concerns. This information is available in publication but is not able to be displayed on this website due to formatting restrictions.	From enrollment through 3 months
Primary	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.
Primary	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
Primary	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	Particpants Who Tolerate Rapid Systolic Blood Pressure Reduction and Maintain Treatment Goals	The ability to maintain the Specified Systolic Blood Pressure Range for the 18-24 Hour Period without Neurological Deterioration or Side Effects	3 months