The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II

NCT02281838 | Terminated Phase 2 DMC

• 1 other identifier: Version 2.0
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 2

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.

Conditions

Intracerebral Hemorrhage

Keywords

Stroke; Hypertension

Outcome Measures

Primary Outcomes (1)

• Diffusion-weighted imaging (DWI) lesion frequency

  48 hours

Secondary Outcomes (3)

• Cumulative diffusion-weighted imaging (DWI) lesion frequency

  30 days post randomization

• Absolute hematoma growth

  24 hours post randomization

• Functional disability as assessed by the Modified Rankin Scale

  90 days post randomization

Study Arms (2)

Target systolic BP <140mmHg

EXPERIMENTAL

Systolic blood pressure will be reduced to \<140 mmHg within 1 hour of randomization.

Drug: labetalol/hydralazine/enalapril

Target systolic BP <180mmHg

ACTIVE COMPARATOR

Systolic blood pressure will be reduced, to \<180 mmHg within 1 hour of randomization.

Drug: labetalol/hydralazine/enalapril

Interventions

labetalol/hydralazine/enalapril DRUG

Blood pressure will be treated with intravenous labetalol (10 mg starting dose)/hydralazine (5 mg starting dose)/enalapril (1.25 mg starting dose).

Target systolic BP <140mmHg; Target systolic BP <180mmHg

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• Patients with suspected secondary cause of ICH.
• 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)

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (2)

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Related Publications (1)

• Gioia L, Klahr A, Kate M, Buck B, Dowlatshahi D, Jeerakathil T, Emery D, Butcher K. The intracerebral hemorrhage acutely decreasing arterial pressure trial II (ICH ADAPT II) protocol. BMC Neurol. 2017 May 19;17(1):100. doi: 10.1186/s12883-017-0884-4.

  PMID: 28525977 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Stroke; Hypertension

Interventions

Labetalol

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)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: November 4, 2014
• Study Start: August 1, 2011
• Primary Completion: November 1, 2021
• Study Completion: December 1, 2021
• Last Updated: November 6, 2024

Record last verified: 2024-11

Locations

CA (2)