Blood Pressure Control for Stroke

(ENCHANTED3/MT Trial)

Recruiting at 1 trial location

Overseen By Xiaoying Chen, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The George Institute

Disqualifiers: Contraindications to BP lowering

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 90 days

2000 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for blood pressure control in stroke patients?

Research shows that intensive systolic blood pressure control can improve outcomes in some patients, as seen in the STEP trial, but it may not be beneficial for all, especially those with higher initial blood pressure or after certain stroke treatments, as indicated by the SPRINT and BP TARGET trials. ^{1 2 3 4 5}

Is intensive blood pressure control generally safe for humans?

Intensive blood pressure control can lead to serious falls and fainting in some people, especially if their blood pressure becomes too low. There is also a risk of increased mortality in patients with higher initial blood pressure and lower cardiovascular risk when using intensive control. ^{1 3 5 6 7}

How does the treatment for blood pressure control in stroke patients differ from other treatments?

This treatment for blood pressure control in stroke patients is unique because it involves different levels of systolic blood pressure (SBP) management, including conservative, moderate, and intensive control, which are tailored to the patient's baseline SBP and cardiovascular risk. Intensive SBP control has shown a trend of reducing the risk of major adverse cardiovascular events and cerebrovascular diseases, although it may not significantly reduce overall cardiovascular and cerebrovascular disease risk compared to standard control. ^{1 2 8 9 10}

What is the purpose of this trial?

Several clinical trials have produced variable conclusions regarding the effects of intensive blood pressure (BP) lowering in post-EVT acute ischaemic stroke (AIS) patients. Although two trials indicate harm from very intensive target-based treatment (SBP \<130 mmHg), the others neutral effects in the SBP range 140-160 mmHg. The ENCHANTED3/MT domain of the ACT-GLOBAL platform trial aims to test different approaches to the treatment of elevated SBP in post-EVT AIS patients to find an optimal BP management strategy. ENCHANTED3/MT will randomize (1:1:1) up to 2,000 patients with SBP ≥150 mmHg post-EVT to conservative (no or minimal SBP reduction by 5-10mmHg or a target of 175-180mmHg if very-high baseline SBP \[≥180mmHg\]), moderate (SBP reduction by 10-20mmHg or a target of 160 ± 5, whichever is higher; no control if low-high baseline SBP \[150-160mmHg\]), or intensive (SBP reduction by 30-50mmHg or a target of 140±5 mmHg, whichever is higher) BP management.

Research Team

Craig Anderson, PhD

Principal Investigator

The George Institute

Eligibility Criteria

This trial is for adults over 18 who've had a stroke treated with endovascular therapy (EVT) within the last day and have high blood pressure (BP ≥150 mmHg). They must not have other conditions that would exclude them from the study.

Inclusion Criteria

I received a special blood vessel procedure within 24 hours of my symptoms starting.

My blood pressure was 150 or higher after a procedure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of three blood pressure management strategies: conservative, moderate, or intensive, to manage elevated SBP post-EVT in AIS patients.

Up to 90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary outcome measured at 90 days.

90 days

Adaptive Analysis

Adaptive analyses are conducted every 3 months with prespecified statistical triggers for superiority, inferiority, and equivalence.

Treatment Details

Interventions

• Conservative SBP Control
• Intensive SBP Control
• Moderate SBP Control

Trial Overview The trial is testing three ways to manage high blood pressure after EVT for stroke: conservative control, moderate control, and intensive control. Patients will be randomly assigned in equal numbers to one of these strategies to find the best BP management approach.

Participant Groups

Group I: Moderate SBP Control Experimental Treatment 1 Intervention

Group II: Intensive SBP Control Experimental Treatment 1 Intervention

Group III: Conservative SBP Control Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

The George Institute

Lead Sponsor

Trials

84

Recruited

275,000+

University of Calgary

Collaborator

Trials

827

Recruited

902,000+

Changhai Hospital

Collaborator

Trials

417

Recruited

553,000+

Findings from Research

In a post hoc analysis of the SPRINT trial involving 9361 participants, intensive blood pressure treatment (targeting SBP <120 mmHg) in patients with a baseline SBP of at least 160 mmHg and lower cardiovascular risk was linked to a higher rate of all-cause death compared to standard treatment (targeting SBP <140 mmHg).

Specifically, the intensive treatment group had an annual death rate of 1.86% versus 1.62% in the standard group, with a hazard ratio of 3.12, indicating a significant increase in mortality risk for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased mortality with intensive control in patients with higher baseline SBP and lower Framingham risk. Pan, HY., Lin, HJ., Chen, WJ., et al.[2022]

In the STEP trial involving 8283 elderly patients with hypertension, high baseline levels of LDL-C and non-HDL-C were linked to a higher risk of cardiovascular events, indicating that lipid levels can influence cardiovascular risk.

However, the benefits of intensive systolic blood pressure control (targeting 110 to <130 mmHg) were consistent regardless of baseline LDL-C and non-HDL-C levels, suggesting that intensive blood pressure management is effective for all patients, irrespective of their lipid profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of baseline serum cholesterol with benefits of intensive blood pressure control. Wang, X., Feng, Y., Yang, L., et al.[2023]

In a post hoc analysis of the BP TARGET trial involving 318 patients, intensive systolic blood pressure (SBP) treatment after endovascular therapy showed no overall benefit, but diabetic patients may experience a trend towards improved outcomes from this treatment.

Factors such as age, occlusion location, and history of hypertension did not influence the effectiveness of intensive SBP treatment, highlighting that diabetes may play a significant role in modifying treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intensive systolic blood pressure lowering after successful endovascular therapy: a post hoc analysis of the BP TARGET trial. Anadani, M., Maier, B., Escalard, S., et al.[2023]

Lowering systolic blood pressure (SBP) to 120-129 mm Hg is associated with a reduced risk of stroke and major cardiovascular events compared to higher SBP levels, based on a network meta-analysis of 14 trials involving 44,015 patients.

Further reduction of SBP to below 120 mm Hg can significantly decrease stroke risk, but maintaining SBP above 150 mm Hg increases the risk of myocardial infarction and cardiovascular mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining the Optimal Systolic Blood Pressure for Hypertensive Patients: A Network Meta-analysis. Fei, Y., Tsoi, MF., Cheung, BMY.[2019]

In a study of 477,516 treated hypertensive individuals, those with a minimum systolic blood pressure (SBP) below 110 mmHg had a significantly higher risk of serious falls and syncope, with an odds ratio of 2.18, indicating more than double the risk compared to those with SBP of 110 mmHg or higher.

The findings suggest that while intensive blood pressure control is important, maintaining SBP above 110 mmHg may be crucial to prevent adverse outcomes like serious falls and syncope in hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Systolic Blood Pressure From Treatment and Association With Serious Falls/Syncope. Sim, JJ., Zhou, H., Bhandari, S., et al.[2019]

In a study of 6427 older patients (average age 80) with hypertension, the best cardiovascular outcomes were observed in those with an average systolic blood pressure (SBP) of 120-129 mmHg, indicating a J-shaped relationship between SBP and adverse events.

Maintaining an SBP of less than 130 mmHg was linked to improved health outcomes without significant safety issues, supporting the recommendation to target this level in older patients if they can tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular outcomes according to on-treatment systolic blood pressure in older hypertensive patients: a multicenter cohort using a common data model. Kim, JH., Joo, HJ., Chung, SH., et al.[2023]

In the SPRINT study involving 9068 participants, intensive blood pressure treatment initially reduced the risk of serious cardiovascular events, but this benefit diminished after about 3.4 years of follow-up.

Factors such as cumulative systolic blood pressure and serious adverse events during treatment may negatively impact the long-term efficacy of intensive hypertension management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cumulative SBP and serious adverse events on efficacy of intensive blood pressure treatment: a randomized clinical trial. Rueda-Ochoa, OL., Rojas, LZ., Ahmad, S., et al.[2022]

Lowering systolic blood pressure (SBP) to 160 mmHg or less using intravenous nicardipine in patients with acute intracerebral hemorrhage (ICH) was found to be safe and well tolerated, with only 0.9% experiencing serious adverse effects.

In a study of 211 patients, neurological deterioration occurred in only 8.1% of cases, and the rates of hematoma expansion and death were within expected ranges, suggesting that this treatment approach is effective in managing blood pressure without significant risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systolic blood pressure lowering to 160 mmHg or less using nicardipine in acute intracerebral hemorrhage: a prospective, multicenter, observational study (the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-Intracerebral Hemorrhage study). Koga, M., Toyoda, K., Yamagami, H., et al.[2022]

Maintaining proper cerebral perfusion pressure is crucial in treating acute neurological diseases, as it helps preserve brain function during conditions like hypertensive encephalopathy and stroke.

In cases of ischemic stroke, blood pressure should be gradually reduced over several days to avoid complications, and the ideal antihypertensive medication should precisely control blood pressure without causing severe hypotension or negatively affecting intracranial pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of hypertension in acute neurological diseases]. Kadojić, D.[2009]

In a study of 3,628 hypertensive patients in China, only 5% achieved intensive systolic blood pressure (SBP) control (≤130 mmHg), but those with higher education, healthier diets, and combination treatments were more likely to meet this goal.

While there was a trend indicating that more intensive SBP control could reduce the risk of major adverse cardiovascular events and cerebrovascular diseases, the study found no significant overall risk reduction for these outcomes compared to standard SBP control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study on the associations of meeting intensive systolic blood pressure control goals with risk for incident cardiovascular and cerebrovascular diseases among the adult hypertensive patients in China]. Yang, HM., Zhao, YX., Lyu, J., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Increased mortality with intensive control in patients with higher baseline SBP and lower Framingham risk. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Association of baseline serum cholesterol with benefits of intensive blood pressure control. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intensive systolic blood pressure lowering after successful endovascular therapy: a post hoc analysis of the BP TARGET trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Determining the Optimal Systolic Blood Pressure for Hypertensive Patients: A Network Meta-analysis. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Low Systolic Blood Pressure From Treatment and Association With Serious Falls/Syncope. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Cardiovascular outcomes according to on-treatment systolic blood pressure in older hypertensive patients: a multicenter cohort using a common data model. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of cumulative SBP and serious adverse events on efficacy of intensive blood pressure treatment: a randomized clinical trial. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Systolic blood pressure lowering to 160 mmHg or less using nicardipine in acute intracerebral hemorrhage: a prospective, multicenter, observational study (the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-Intracerebral Hemorrhage study). [2022]

9. Croatia pubmed.ncbi.nlm.nih.gov

[Treatment of hypertension in acute neurological diseases]. [2009]

10. China pubmed.ncbi.nlm.nih.gov

[Study on the associations of meeting intensive systolic blood pressure control goals with risk for incident cardiovascular and cerebrovascular diseases among the adult hypertensive patients in China]. [2023]