The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alberta
• Treatments: Enalapril; Enalaprilat; Hydralazine; Labetalol

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)