Intensive Ambulance-delivered Blood Pressure Reduction in Hyper-Acute Stroke Trial (INTERACT4)

A multicentre, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) study to assess the effects of hyperacute intensive blood pressure (BP) lowering initiated in ambulance setting on (i) functional outcome in patients with acute stroke (ii) safety in patients with confirmed acute stroke and other conditions that were initially suspected as acute stroke (i.e. stroke mimic).

Study Overview

• Status: Completed
• Conditions: Cerebrovascular Disorders; Stroke, Acute
• Intervention / Treatment: Drug: urapidil

Detailed Description

As an investigator initiated and conducted, multicentre, ambulance-delivered, prospective, randomised, open-label, blinded outcome (PROBE) study. INTERACT4 aims to evaluate the effects of functional outcome according to an ordinal analysis of the full range of scores on the mRS, the safety in all randomised patients; reperfusion treatment (thrombolysis and/or thrombectomy) related symptomatic ICH (sICH, according to standard definitions), infarct size, the time to and overall rate of reperfusion treatment in AIS patients; hematoma volume and early expansion in ICH.

• Study Type: Interventional
• Enrollment (Actual): 2425
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lily Song; Phone Number: +86 13916466400; Email: lsong@georgeinstitute.org.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100088
      • The George Institute for Global Health
  • Shanghai
    • Shanghai, Shanghai, China, 200123
      • Shanghai East Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China
    • Chengdu, Sichuan, China, 610500
      • The First Affliated Hospital of Chengdu Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age ≥18 years;
2. Acute syndrome that is due to presumed acute stroke, defined as FAST（Face, Arm, Speech, Time） scores of ≥2 with an arm motor deficit and time ≤2 hours from last seen well;
3. Systolic BP ≥150
4. Able to provide brief informed consent (if a waver of consent is not approved by the ethics committee)

Exclusion Criteria:

1. Coma - no response to tactile stimuli or verbal stimuli;
2. Severe co-morbid disease (e.g. cancer, chronic airflow disease, severe dementia,severe heart failure,pre-stroke disability[needed help]);
3. History of epilepsy or seizure at onset;
4. History of recent head injury (<7 days);
5. Hypoglycemia(glucose<2.8mmol/L)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; If systolic blood pressure>180:IV Urapidil 25mg If systolic blood pressure>150 (or 5 mins after first bolus) : IV Urapidil 25mg and to maintain this level after admission to hospital in those with confirmed acute stroke for the next 7 days (or hospital discharge if earlier)	Drug: urapidil; A standard treatment regime based on intravenous (IV) bolus of 25mg urapidil administered over 1 minute. For those patients initial systolic blood pressure 180, another 25mg urapidil bolus will be given if the systolic blood pressure level persists >150 after 5 minutes.; Other Names: Intensive BP lowing
No Intervention: control group; To receive blood pressure management according to standard local guidelines which recommend blood pressure lowering in hospital if systolic level is >220mmHg. This level will be considered by ambulance staff as a threshold for treatment if considered clinically important.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
level of physical function	Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with serious adverse events	total number of serious adverse events reported during follow-up, according to standard definitions	Day 90
number of patients with any intracranial hemorrhage	reperfusion treatment (thrombolysis/thrombectomy) related symptomatic intracerebral number of cases of intracranial hemorrhage, according to standard definitions	Day 7
size of cerebral infarction	overall size of cerebral infarction on MRI within 2 days in cases of ischaemic stroke	Day 2
number of patients who receive reperfusion treatment	total number of cases of reperfusion (thrombolysis and/or thrombectomy) in ischemic stroke	Day 0
time to use of reperfusion treatment	time from symptom onset to reperfusion treatment in patients with ischemic stroke	Day 0
size of hematoma volume	change in volume of hematoma from baseline to 24 hours, measured on brain imaging	Day 1
size of hematoma volume	volume of hematoma at baseline measured on brain imaging	Day 0
death or major disability	Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death. mRS(3-6)	Day 90
Death		Day 90
Disability	Level of function defined across 7 categories of disability on the modified Rankin scale （mRS 0-6) in which scores of 0 or 1 indicate good function without or with symptoms but not disability, socress of 2 indicates slight disability but independence, 3 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.	Day 90
death or dependency measured by a shift in NIHSS		day 1 and day 7
Health related quality of life	according to the EQ-5D	day 90

Collaborators and Investigators

• Sponsor: The George Institute for Global Health, China
• Collaborators: Shanghai East Hospital, China; First Affiliated Hospital of Chengdu Medical College, China; Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China
• Investigators: Principal Investigator: Craig Anderson, The George Institute for Global Health, China; Principal Investigator: Gang Li, Shanghai East Hospital, China; Principal Investigator: Jie Yang, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China; Principal Investigator: Yapeng Lin, The First Affliated Hospital of Chengdu Medical College, China

Publications and helpful links

General Publications

• Song L, Chen C, Chen X, Guo Y, Liu F, Lin Y, Billot L, Li Q, Liu H, Si L, Ouyang M, Arima H, Bath PM, Ford GA, Robinson T, Sandset EC, Saver JL, Sprigg N, van der Worp HB, Zhang C, Yang J, Li G, Anderson CS; INTERACT4 investigators. INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): study protocol for a randomized controlled trial. Trials. 2021 Dec 6;22(1):885. doi: 10.1186/s13063-021-05860-y.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2020
• Primary Completion (Actual): November 23, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: December 26, 2018
• First Submitted That Met QC Criteria: December 29, 2018
• First Posted (Actual): January 2, 2019

Study Record Updates

• Last Update Posted (Estimated): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 23, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: stroke; hypertension; clinical trial; blood pressure control; ambulances
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Cerebrovascular Disorders; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Serotonin Agents; Serotonin Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Urapidil
• Other Study ID Numbers: INTERACT4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared with bona fide researchers after 1 year following conclusion of the study, based on a submitted protocol to the research office of The George Institute for Global Health, Sydney Australia
• IPD Sharing Time Frame: 1 year after conclusion of the study
• IPD Sharing Access Criteria: genuine researcher with supporting institution protocol review and approval by the research office of The George Institute
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No