Ignite Creation Date:
2024-05-06 @ 3:25 AM
Last Modification Date:
2024-10-26 @ 11:33 AM
Study NCT ID:
NCT02281838
Status:
RECRUITING
Last Update Posted:
2024-04-05
First Post:
2014-10-29
Brief Title:
The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II
Sponsor:
University of Alberta
Organization:
University of Alberta
Study Overview
Official Title:
The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ICH-ADAPT II
Brief Summary:
The vast majority of intracerebral hemorrhage ICH patients present with elevated blood pressureBP Management of BP is controversial with two competing rationales There is some evidence that hyperacute treatment may improve outcomes by reducing the rate of hematoma expansion Physicians have been reluctant to reduce BP early after ICH onset fearing reduced cerebral blood flow CBF will increase ischemia and increase the risk of further damage Other confounding mediators to further ischemic injury following ICH include increased platelet activity withdrawal of antithrombotic therapy endothelial dysfunction inflammation and hypercoagulability
This study is phase II of the ICH-ADAPT study The investigators hypothesize that aggressive antihypertensive therapy will alter the natural history of heamatoma growth improving outcomes after Intracranial Hemorrhage ICH The previous phase I ICH-ADAPT study has established the safety of early BP treatment
The investigators have designed a phase II study in which ICH patients are randomized to aggressive versus conservative BP treatment using a deferred consent procedure An adaptive randomization will be used to treat BP to 140 mmHg SBP or 180 mmHg SBP Treatment must be implemented as soon as possible after radiological confirmation of diagnosis Antihypertensive therapy must begin within 6 hours of symptom onset The patient will be re-imaged 24 hours later The patient will have continuous non-invasive BP and heart rateHR monitoring for a minimum of 24 hours Antihypertensive drug use and dosage will be recorded with BP and HR Patients will be monitored regularly until study completion MRIs will be done at 48 hours day 7 and day 30 This imaging will help to detect ischemic changes that may occur Blood will be collected at the same time as the MRI Blood analysis will be done to possibly identify biomarkers that may be putative mediators of ischemic injury in ICH patients
This study is phase II of the ICH-ADAPT study The investigators hypothesize that aggressive antihypertensive therapy will alter the natural history of heamatoma growth improving outcomes after Intracranial Hemorrhage ICH The previous phase I ICH-ADAPT study has established the safety of early BP treatment
The investigators have designed a phase II study in which ICH patients are randomized to aggressive versus conservative BP treatment using a deferred consent procedure An adaptive randomization will be used to treat BP to 140 mmHg SBP or 180 mmHg SBP Treatment must be implemented as soon as possible after radiological confirmation of diagnosis Antihypertensive therapy must begin within 6 hours of symptom onset The patient will be re-imaged 24 hours later The patient will have continuous non-invasive BP and heart rateHR monitoring for a minimum of 24 hours Antihypertensive drug use and dosage will be recorded with BP and HR Patients will be monitored regularly until study completion MRIs will be done at 48 hours day 7 and day 30 This imaging will help to detect ischemic changes that may occur Blood will be collected at the same time as the MRI Blood analysis will be done to possibly identify biomarkers that may be putative mediators of ischemic injury in ICH patients
Detailed Description:
Study Design multi-centre randomized open-label blinded-endpoint trial of two different BP management strategies This study is being conducted in the Emergency Departments and Stroke Units of Canadian academic and non-academic centres
Overall Aim and Hypothesis The primary study aim is to assess the rate of ischemic lesion development in patients randomized to two different BP treatment strategies The overall a priori hypothesis is that aggressive BP reduction will not be associated with ischemic injury after ICH
Patients Male and female patients will be recruited from Emergency Departments of participating hospitals A total of 270 patients will be included over 3 years
Baseline Data and Randomization Demographics Glasgow Coma Scale GCS and National Institutes of Health Stroke Scale NIHSS scores both of which are part of routine stroke patient assessment time of symptom onset and diagnostic CT scan will all be recorded If the CT scan is completed within 6 hours of onset and confirms evidence of a primary ICH patients will be randomized Where patients are incompetent and surrogate decision makers are not immediately available randomization will occur using a deferred consent procedure Stroke risk factors past medical history and medications with emphasis on antihypertensives as well as standard clinical blood work complete blood count and coagulation profile will be recorded after randomization in order to avoid delays to BP treatment
Intervention - Blood Pressure Management Protocols
Aggressive BP Target 140 mmHg Treatment Group Patients randomized to the 140 mmHg group n135 will immediately receive a 10 mg IV bolus of labetalol administered over 1 minute A protocol designed to achieve and maintain systolic BP 140 mmHg within 60 minutes of randomization has been designed Appendix 5 A key feature of this protocol is the utilization of IV enalapril which can be given regularly Q 6 hourly avoiding BP fluctuations a problem which has been noted previously when using bolus-based protocols109 Patients randomized to the 140 mmHg group will be treated with 125 mg of IV enalapril immediately after labetalol administration A lower limit of 120 mmHg has been stipulated although given the investigators experience in ICH ADAPT I this is unlikely to be achieved In the event of systolic BP falling below 120 mmHg antihypertensive therapy will be held and patients will be fluid resuscitated with isotonic saline Pressor agents will not be used
Conservative BP Target 180 mmHg Treatment Group Patients randomized to the 180 mmHg group n135 will be administered parenteral antihypertensive therapy only if systolic BP is 180 mmHg consistent with current guidelines
All patients will have continuous non-invasive BP and heart rate HR monitoring for a minimum of 24h BP and HR will be recorded most intensively during the hyperacute phase as per the NINDS r-tPA protocol for vital signs monitoring Antihypertensive drug use and dosages will be recorded concomitantly with BP and HR Patients will be monitored regularly until study completion Door-to-needle times will be documented with respect to the initiation of antihypertensive medication and the proportion of patients achieving BP targets within 1 hour of treatment
At completion of the 24h active treatment period all patients will continue to receive standard stroke care and rehabilitation and treating physicians will manage BP in the manner they feel is appropriate Physicians will be encouraged to start oral antihypertensive therapy administered via nasogastric feeding tube if necessary on day 2 BP HR and antihypertensive medication doses will continue to be monitored and recorded every 4 h for the first 48 h and then twice daily until discharge Long-term goals for both patient groups after the active treatment period are a systolic BP of 140 mmHg or 130 mmHg in those with diabetes as per current stroke prevention and hypertension guidelines
Imaging Procedures
Baseline - Immediately prior to randomization and BP reduction patients will undergo a standard non-contrast CT diagnostic brain scan In the event of early neurological deterioration at any point a repeat CT scan will be obtained immediately
24 hour CT - All patients will have a repeat CT brain scan at 243 h in order to assess for hematoma expansion and peri-hematoma edema volume
48 hour MRI - At 4812 h patients will undergo MRI scanning including a T1-weighted sagittal localizer DWI Gradient Recalled Echo GRESusceptibility Weighted Imaging SWI diffusion-weighted DWI and perfusion-weighted images PWI
Day 7 MRI Scan Secondary Endpoint - A repeat MRI will be obtained at 72 days to assess for new DWI lesion development and evolution of those identified at 24 hours
Day 30 MRI Scan Secondary Endpoint - A repeat MRI will be obtained at 305 days to assess for new DWI lesion development and evolution of those identified at 24 hours and 7 days
Clinical Assessments
In Hospital - In addition to BP data GCS and NIHSS scores will be collected in the event of early neurological deterioration Both of these scores will also be recorded at the time of each MRI scan and at hospital discharge or transfer to alternate level of care ie rehabilitation or long-term care facility Discharge modified Rankin Scores mRS will also be recorded Cognitive changes will be assessed with the Montreal Cognitive Assessment MoCA at the time of each MRI scan
Follow-up Day 30 - A standardized interview aimed at determining mortality and current residence of the patient homehospitalrehabilitation hospitallong-term care facility will be administered at the time of the day 30 MRI The NIHSS and MoCA scores will also be recorded as will modified Rankin scale mRS scores Quality of life will be assessed with the EQ-5D
Day 90 - This is the standard time point for measuring functional outcomes in stroke trials as the bulk of neurological recovery occurs within that time frame All neurological functional and cognitive disability tests will be repeated at this time
Overall Aim and Hypothesis The primary study aim is to assess the rate of ischemic lesion development in patients randomized to two different BP treatment strategies The overall a priori hypothesis is that aggressive BP reduction will not be associated with ischemic injury after ICH
Patients Male and female patients will be recruited from Emergency Departments of participating hospitals A total of 270 patients will be included over 3 years
Baseline Data and Randomization Demographics Glasgow Coma Scale GCS and National Institutes of Health Stroke Scale NIHSS scores both of which are part of routine stroke patient assessment time of symptom onset and diagnostic CT scan will all be recorded If the CT scan is completed within 6 hours of onset and confirms evidence of a primary ICH patients will be randomized Where patients are incompetent and surrogate decision makers are not immediately available randomization will occur using a deferred consent procedure Stroke risk factors past medical history and medications with emphasis on antihypertensives as well as standard clinical blood work complete blood count and coagulation profile will be recorded after randomization in order to avoid delays to BP treatment
Intervention - Blood Pressure Management Protocols
Aggressive BP Target 140 mmHg Treatment Group Patients randomized to the 140 mmHg group n135 will immediately receive a 10 mg IV bolus of labetalol administered over 1 minute A protocol designed to achieve and maintain systolic BP 140 mmHg within 60 minutes of randomization has been designed Appendix 5 A key feature of this protocol is the utilization of IV enalapril which can be given regularly Q 6 hourly avoiding BP fluctuations a problem which has been noted previously when using bolus-based protocols109 Patients randomized to the 140 mmHg group will be treated with 125 mg of IV enalapril immediately after labetalol administration A lower limit of 120 mmHg has been stipulated although given the investigators experience in ICH ADAPT I this is unlikely to be achieved In the event of systolic BP falling below 120 mmHg antihypertensive therapy will be held and patients will be fluid resuscitated with isotonic saline Pressor agents will not be used
Conservative BP Target 180 mmHg Treatment Group Patients randomized to the 180 mmHg group n135 will be administered parenteral antihypertensive therapy only if systolic BP is 180 mmHg consistent with current guidelines
All patients will have continuous non-invasive BP and heart rate HR monitoring for a minimum of 24h BP and HR will be recorded most intensively during the hyperacute phase as per the NINDS r-tPA protocol for vital signs monitoring Antihypertensive drug use and dosages will be recorded concomitantly with BP and HR Patients will be monitored regularly until study completion Door-to-needle times will be documented with respect to the initiation of antihypertensive medication and the proportion of patients achieving BP targets within 1 hour of treatment
At completion of the 24h active treatment period all patients will continue to receive standard stroke care and rehabilitation and treating physicians will manage BP in the manner they feel is appropriate Physicians will be encouraged to start oral antihypertensive therapy administered via nasogastric feeding tube if necessary on day 2 BP HR and antihypertensive medication doses will continue to be monitored and recorded every 4 h for the first 48 h and then twice daily until discharge Long-term goals for both patient groups after the active treatment period are a systolic BP of 140 mmHg or 130 mmHg in those with diabetes as per current stroke prevention and hypertension guidelines
Imaging Procedures
Baseline - Immediately prior to randomization and BP reduction patients will undergo a standard non-contrast CT diagnostic brain scan In the event of early neurological deterioration at any point a repeat CT scan will be obtained immediately
24 hour CT - All patients will have a repeat CT brain scan at 243 h in order to assess for hematoma expansion and peri-hematoma edema volume
48 hour MRI - At 4812 h patients will undergo MRI scanning including a T1-weighted sagittal localizer DWI Gradient Recalled Echo GRESusceptibility Weighted Imaging SWI diffusion-weighted DWI and perfusion-weighted images PWI
Day 7 MRI Scan Secondary Endpoint - A repeat MRI will be obtained at 72 days to assess for new DWI lesion development and evolution of those identified at 24 hours
Day 30 MRI Scan Secondary Endpoint - A repeat MRI will be obtained at 305 days to assess for new DWI lesion development and evolution of those identified at 24 hours and 7 days
Clinical Assessments
In Hospital - In addition to BP data GCS and NIHSS scores will be collected in the event of early neurological deterioration Both of these scores will also be recorded at the time of each MRI scan and at hospital discharge or transfer to alternate level of care ie rehabilitation or long-term care facility Discharge modified Rankin Scores mRS will also be recorded Cognitive changes will be assessed with the Montreal Cognitive Assessment MoCA at the time of each MRI scan
Follow-up Day 30 - A standardized interview aimed at determining mortality and current residence of the patient homehospitalrehabilitation hospitallong-term care facility will be administered at the time of the day 30 MRI The NIHSS and MoCA scores will also be recorded as will modified Rankin scale mRS scores Quality of life will be assessed with the EQ-5D
Day 90 - This is the standard time point for measuring functional outcomes in stroke trials as the bulk of neurological recovery occurs within that time frame All neurological functional and cognitive disability tests will be repeated at this time
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None