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The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II (ICH-ADAPT II)

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ClinicalTrials.gov Identifier: NCT02281838
Recruitment Status : Recruiting
First Posted : November 4, 2014
Last Update Posted : April 5, 2018
Sponsor:
Information provided by (Responsible Party):
Ken Butcher, University of Alberta

Brief Summary:

The vast majority of intracerebral hemorrhage (ICH) patients present with elevated blood pressure(BP). 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 rate(HR) 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. MRI's 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.


Condition or disease Intervention/treatment Phase
Intracerebral Hemorrhage Drug: labetalol/hydralazine/enalapril Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II
Study Start Date : November 2012
Estimated Primary Completion Date : December 2018


Arm Intervention/treatment
Experimental: Target systolic BP <140mmHg
Systolic blood pressure will be reduced to <140 mmHg within 1 hour of randomization.
Drug: labetalol/hydralazine/enalapril
Blood pressure will be treated with intravenous labetalol (10 mg starting dose)/hydralazine (5 mg starting dose)/enalapril (1.25 mg starting dose).

Active Comparator: Target systolic BP <180mmHg
Systolic blood pressure will be reduced, to <180 mmHg within 1 hour of randomization.
Drug: labetalol/hydralazine/enalapril
Blood pressure will be treated with intravenous labetalol (10 mg starting dose)/hydralazine (5 mg starting dose)/enalapril (1.25 mg starting dose).




Primary Outcome Measures :
  1. Diffusion-weighted imaging (DWI) lesion frequency [ Time Frame: 48 hours ]

Secondary Outcome Measures :
  1. Cumulative diffusion-weighted imaging (DWI) lesion frequency [ Time Frame: 30 days post randomization ]
  2. Absolute hematoma growth [ Time Frame: 24 hours post randomization ]
  3. Functional disability as assessed by the Modified Rankin Scale [ Time Frame: 90 days post randomization ]
    Modified Rankin scale (0=no symptoms, 1=no significant disability, 2=slight disability, 3=moderate disability, 4=moderately severe disability, 5=severe disability, 6=dead)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years
  • Acute primary ICH demonstrated with CT scan, within 6 h of symptom onset.
  • Two systolic BP measurements ≥140 mmHg recorded >2 min apart to qualify for enrolment.
  • Onset ≤ 24 h prior to randomization

Exclusion Criteria:

  • Contraindication to BP reduction i.e., severe arterial stenosis or high-grade stenotic valvular heart disease
  • Indication for urgent BP reduction i.e., hypertensive encephalopathy, or aortic dissection
  • Definite evidence that the ICH is secondary to underlying cerebral or vascular pathology, i.e., AVM, aneurysm, tumour, trauma, vasculitis, or hemorrhagic transformation of an ischemic infarct
  • Previous ischemic stroke within 90 days of current event NB: Prior ICH is not an exclusion criterion
  • Patients with suspected secondary cause of ICH.
  • Planned surgical resection of hematoma NB: Extraventricular Drain placement is not an exclusion criterion
  • Contraindication to CT perfusion imaging (i.e. contrast allergy, metformin use or Creatinine >160 μmol/l)
  • Patients with pre-existing disability and dependence (defined as a pre-morbid modified Rankin Scale score ≥3) will be excluded
  • Patients with life expectancy <6 months due to pre-morbid conditions/terminal illness
  • Patients with known definite contraindications to MRI (pacemaker, ferrous metallic foreign body)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02281838


Contacts
Contact: Ken S Butcher, MD, 7804072171 ken.butcher@ualberta.ca

Locations
Canada, Alberta
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Ken S Butcher, MD, PhD    7804072171    ken.butcher@ualberta.ca   
Principal Investigator: Ken S Butcher, MD, PhD         
Canada, Ontario
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4E9
Contact: Dar Dowlatshahi    613-761-4709    ddowlat@toh.on.ca   
Principal Investigator: Dar Dowlatshahi, MD         
Sponsors and Collaborators
University of Alberta

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ken Butcher, Assistant Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT02281838     History of Changes
Other Study ID Numbers: Version 2.0
First Posted: November 4, 2014    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: April 2018

Keywords provided by Ken Butcher, University of Alberta:
Stroke
Hypertension

Additional relevant MeSH terms:
Antihypertensive Agents
Hemorrhage
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Enalapril
Enalaprilat
Hydralazine
Labetalol
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists