Outcome in Patients Treated With Intraarterial Thrombectomy - optiMAL Blood Pressure Control (OPTIMAL-BP)

• ClinicalTrials.gov Identifier: NCT04205305
• Recruitment Status: Active, not recruiting
• First Posted: December 19, 2019
• Last Update Posted: March 30, 2023
• Sponsor: Yonsei University
• Information provided by (Responsible Party): Yonsei University

Study Description

Brief Summary:

Recent endovascular thrombectomy (EVT) trial have proven the effectiveness of intraarterial revascularization in patients with larger cerebral artery occlusion. The success rate of EVT is close to 80%, but only 50% of patients improve to independent functional outcome. Therefore, new treatment strategies are needed to reduce the futile revascularization. However, updated guidelines recommend the indications for EVT based on the results of randomized clinical trials (RCT), management of post-revascularization is largely unknown.

Current guidelines suggest that systolic blood pressure should be adjusted below 180 mmHg and diastolic blood pressure below 105 mmHg in patients undergoing intraarterial reopening. However, in the case of successful recanalization by EVT, same guideline is adopted even though the possibility of intracerebral hemorrhage or reperfusion injury by high blood pressure. On the other hand, too low blood pressure can worsen cerebral ischemia.

Therefore, this study will compare the effectiveness of active blood pressure control group (with less than 140 mmHg systolic blood pressure) versus standard blood pressure control group (with less than 180 mmHg systolic blood pressure) during the first 24 hours in patients who underwent EVT and achieved successful recanalization (TICI 2b-3). The goal is to reach the target blood pressure within 60 minutes of randomization.

Condition or disease	Intervention/treatment	Phase
Ischemic Stroke	Drug: conventional blood pressure control (labetalol, nicardipine); Drug: intensive blood pressure control (labetalol, nicardipine)	Phase 4

Detailed Description:

1. The study is a multicenter, prospective, randomized, open-label trial with blinded end-point assessment (PROBE) design study.
2. After successful revascularization, the active blood pressure control group and the standard blood pressure control group will be randomized by 1: 1.
3. Patients who is admitted to the Department of Neurology at the participating hospital with acute cerebral infarction will will be included for 5 years from December 2019 to December 2023 (based on the date of stroke). Patients who have undergone intraarterial thrombectomy and have successfully reopened arteries should be enrolled.
4. Collect medical history, laboratory findings and blood pressure parameters (systolic blood pressure, diastolic blood pressure, blood pressure variability, etc.), neurological scores, functional recovery, and quality of life indicators.
5. Neurological scores, functional recovery scores, and quality of life indicators are performed by independent researchers in the blind state.
6. All data is collected using e-CRF, and the image study will be anonymized and sent to the central adjudication.
7. Central adjudication will review the image study.
8. One intermediate analysis will be conducted at the end of first period or when a half of study patients were enrolled.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 306 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

1. The study is a multicenter, prospective, randomized, open-label trial with blinded end-point assessment (PROBE) design study.
2. After successful revascularization, the active blood pressure control group and the standard blood pressure control group will be randomized by 1: 1.
3. Patients who have undergone intraarterial thrombectomy due to acute cerebral infarction and have successfully reopened arteries will be enrolled.
4. Medical history, laboratory findings and blood pressure parameters (systolic blood pressure, diastolic blood pressure, blood pressure variability, etc.), neurological scores, functional recovery, and quality of life indicators will be collected.
5. Neurological scores, functional recovery scores, and quality of life indicators are performed by independent researchers in the blind state.
6. All data is collected using e-CRF, and the image study will be anonymized and sent to the central adjudication.

• Masking: Single (Outcomes Assessor)
• Masking Description: Three months after discharge, the independence assessment will be performed by the researcher who don't know the patients group.
• Primary Purpose: Treatment
• Official Title: Outcome in Patients Treated With Intraarterial Thrombectomy - optiMAL Blood Pressure Control (OPTIMAL-BP)
• Actual Study Start Date: June 18, 2020
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Conventional blood pressure control group; systolic blood pressure <180 mmHg	Drug: conventional blood pressure control (labetalol, nicardipine); After successful recanalization, appropriate antihypertension medication is administered to control systolic blood pressure <180 mmHg.
Experimental: Intensive blood pressure control group; systolic blood pressure <140 mmHg	Drug: intensive blood pressure control (labetalol, nicardipine); After successful recanalization, appropriate antihypertension medication is administered to control systolic blood pressure <140 mmHg.

Outcome Measures

Primary Outcome Measures :

1. Modified Rankin scale scores(mRS) [ Time Frame: 90 days ]

   Effectiveness outcome: Functional independence (modified Rankin score 0 to 2)

   -The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire.

2. symptomatic intracerebral hemorrhage: Number of participants with symptomatic intracerebral hemorrhage [ Time Frame: 36 hours ]
   Safety outcome: The definition in the European Cooperative Acute Stroke Study III (ECASS 3) will be adopted : a large local or remote parenchymal pattern (>30% of the infarcted area affected by hemorrhage, with mass effect or extension outside the infarct), intraventricular hemorrhage, or subarachnoid hemorrhage which is identified as the predominant cause of the neurologic deterioration from baseline (increase of ≥4 points in the NIHSS score) or death within 36 hours.
3. Death related to the index stroke within 90 days [ Time Frame: 90 days ]

Secondary Outcome Measures :

1. BP parameters - systolic blood pressure [ Time Frame: 24 hour ]
   change in systolic blood pressure
2. BP parameters - diastolic blood pressure [ Time Frame: 24 hour ]
   change in diastolic blood pressure
3. BP parameters - blood pressure variability [ Time Frame: 24 hour ]
   change in blood pressure variability
4. Functional independence [ Time Frame: 1 month ]
   modified Rankin score 0 to 2
5. Distribution of the modified Rankin scores (shift analysis) [ Time Frame: 90 days ]
   The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire.
6. National Institutes of Health Stroke Scale(NIHSS) score [ Time Frame: 24 hour ]
   The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment.
7. Excellent recovery [ Time Frame: 24 hour ]
   NIHSS 0 -1 or improvement more than 8. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment.
8. Recanalization status on CT Angiography(CTA) or MR Angiography(MRA) [ Time Frame: 24±12 hour ]

   occurence of TICI 2b or 3 recanalization on CTA or MRA

   - The thrombolysis in cerebral infarction(TICI) scale is a tool for determining the response of thrombolytic therapy for ischemic stroke. The original description 1 was based on the angiographic appearances of the treated occluded vessel and the distal branches(Grade 0: no perfusion, Grade 1: penetration with minimal perfusion, Grade 2: partial perfusion, Grade 2A: only partial filling(less than two-thirds) of the entire vascular territory is visualized, Grade 2B: complete filling of all of the expected vascular territory is visualized but the filling is slower than normal, Grade 3: complete perfusion)

9. Quality of life measured by Euro-QoL [ Time Frame: 90 days ]
   EuroQol-5D (EQ-5D) is an instrument for measuring quality of life. The answers given to ED-5D permit to find 243 unique health states or can be converted into EQ-5D index an utility scores anchored at 0 for death and 1 for perfect health.
10. Number of participants with malignant brain edema [ Time Frame: 24 hour ]
    1) acute, complete MCA(middle cerebral artery) infarction with early parenchymal hypodensity of at least 50% of the MCA territory and signs of local brain swelling such as sulcal effacement and compression of the lateral ventricle; 2) midline shift of >5 mm at the septum pellucidum or pineal gland with obliteration of the basal cisterns; and 3) neurological deterioration consisting of a NIHSS increase by >2 points and decrease in the level of consciousness to a score of ≥ 1 on item 1A of the NIHSS.
11. Number of participants with treatment failure [ Time Frame: 24 hour ]
    failure to achieve goal blood pressure(BP) for 2 consecutive BP measurements during the first 24 hours following EVT(endovascular thrombectomy)
12. CT or MRI ASPECTS(Alberta Stroke Program Early CT Score) [ Time Frame: 36 hour ]

    Alberta Stroke Program Early CT Score(ASPECTS) is a 10-point quantitative score used to assess early ischemic changes on non-contrast CT head.

    To compute the ASPECTS, 1 point is subtracted from 10 for any evidence of early ischemic change for each of the defined regions. Identifying patients with a greater likelihood of poor functional outcome (scores <8) may be helpful in the early stages of care for supporting transfer or therapy decisions.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥20 years
2. Acute ischemic stroke patients who underwent intraarterial treatment for large vessel occlusion. (ICA, MCA M1 or M2, ACA A1, PCA P1)
3. Patients with successful recanalization after intraarterial thrombectomy (TICI 2b or TICI 3) 4. Patients with elevated BP (systolic BP ≥140 mmHg) on at least two measurements with a two-minute interval within 2 hours of successful recanalization.

Exclusion Criteria:

1. Age <20
2. Patients with contraindication for use antihypertensive medication after intraarterial thrombectomy.
3. Patients with blood pressure <140 mmHg after successful recanalization.
4. Patients with symptomatic intracranial hemorrhage after successful recanalization
5. Patients with pre-morbid neurological dysfunction (modified Rankin Scale, mRS >2)
6. Patients with severe medical and surgical diseases.
7. Patients who are considered having a difficulty to enrollment.
8. No informed consents from patients.
9. Patients who participated in a study that did not allow duplicate participation

Contacts and Locations

Locations

Korea, Republic of

Department of Neurology, Yonsei University College of Medicine

Seoul, Korea, Republic of, 120-752

Sponsors and Collaborators

Yonsei University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nam HS, Kim YD, Choi JK, Baik M, Kim BM, Kim DJ, Heo J, Shin DH, Lee KY, Jung YH, Baek JH, Hwang YH, Sohn SI, Hong JH, Park H, Kim CK, Kim GS, Seo KD, Lee K, Seo JH, Bang OY, Seo WK, Chung JW, Chang JY, Kwon SU, Lee J, Kim J, Yoo J, Song TJ, Ahn SH, Cho BH, Cho HJ, Kim JG, Chang Y, Lee CJ, Park S, Park G, Lee HS. Outcome in Patients Treated with Intra-arterial thrombectomy: The optiMAL Blood Pressure control (OPTIMAL-BP) Trial. Int J Stroke. 2021 Aug 29:17474930211041213. doi: 10.1177/17474930211041213. Online ahead of print.

• Responsible Party: Yonsei University
• ClinicalTrials.gov Identifier: NCT04205305
• Other Study ID Numbers: 4-2019-1208
• First Posted: December 19, 2019
• Last Update Posted: March 30, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: This is not a drug comparison study. Therefore IPD will not be shared.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yonsei University:

Acute ischemic stroke; blood pressure; hypertension; endovascular thrombectomy; recanalization

Additional relevant MeSH terms:

Ischemic Stroke; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Labetalol; Nicardipine; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antihypertensive Agents; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Calcium Channel Blockers; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Vasodilator Agents