Early monitoring of intravenous thrombolysis in acute ischaemic stroke using wearable intelligent vital sign devices: protocol for a prospective, multicentre, observational registry cohort study

Abstract

Introduction

Continuous monitoring of vital signs during and after ischaemic stroke was recommended by the ‘Guidelines for the Early Management of Patients with Acute Ischaemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischaemic Stroke’. Vital sign data can be associated with disease conditions and prognosis, while there is limited evidence regarding continuous monitoring of vital signs during and after acute ischaemic stroke. The wearable intelligent vital sign monitoring device is small and lightweight and constantly monitors the health status during daily activities. However, wearable intelligent vital sign monitoring devices have not been widely used in clinical practice so far. Therefore, we will investigate the effectiveness and safety of wearable intelligent vital sign monitoring devices in early in-hospital management and monitoring programmes for patients with acute ischaemic stroke. This paper presents the study protocol.

Methods and design

This study is a prospective, multicentre, observational registry study starting from 20 March 2023 to 20 March 2025. A total of 5740 patients with acute ischaemic stroke from 10 Chinese hospitals are planned to be enrolled. Continuous vital sign data, demographics, medical history, medication history, treatments, laboratory tests, imaging scans and follow-up data will be collected. Follow-up time points were 30 days after discharge, 30 days after intravenous thrombolysis, 3 months after intravenous thrombolysis and 12 months after intravenous thrombolysis (until March 2026). The primary outcome included the evaluation of the modified Rankin Scale at 3 months, as well as the assessment of the rate of symptomatic and asymptomatic intracranial haemorrhage throughout the hospitalisation period.

Ethics and dissemination

This study has been approved by the Medical Ethics Committee of Xuanwu Hospital, Capital Medical University ([2022] 203). We plan to disseminate the research findings through publication in peer-reviewed scientific journals and presentations at international conferences.

Trial registration number

ChiCTR2300069512.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• A large number of vital sign parameters will be monitored, encompassing respiratory rate, systolic and diastolic blood pressure, heart rate and oxygen saturation, rather than relying solely on a solitary vital sign.

• Substantial sample sizes will be enlisted: an estimated 5740 cases of patients with acute ischaemic stroke, who have received intravenous thrombolysis treatment.

• A prospective design will be adopted, encompassing consecutive patients and mitigating selection bias.

• As an observational study, there is a possibility of residual confounding factors.

• This research exclusively takes place in China and aims to recruit participants from the local population, which may limit the generalisability of the findings.

Introduction

According to the 2019 Global Burden of Disease study, stroke is the second leading cause of death and the third leading cause of disability in the world.¹ Importantly, it is the first cause of death and disability among Chinese adults.² Ischaemic stroke (IS) is the most common stroke type, accounting for 69.6% of all cases.³ Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is one of the most effective drug therapies to improve the outcome of patients with AIS and has been recommended by international clinical guidelines.⁴ It has also been proposed that the vital signs of patients with stroke should be continuously monitored during intravenous thrombolytic therapy and 24 hours after thrombolytic therapy.⁴ These measured objective values can be associated with patients’ real-time status.⁵ With the rapid development of science and technology, wearable devices are gradually being applied in medical care.⁶ A combination of wearable devices and vital sign monitoring enables remote monitoring of heart rate, blood pressure and/or respiration, exerting a beneficial effect on reducing serious adverse events and improving clinical outcomes.⁷ Although vital sign monitoring technology can be intelligent, it has not been widely used in clinical practice.^{8 9} At present, registration studies regarding continuous vital sign monitoring based on wearable devices are lacking, and thus, it is difficult to explore the relationship between vital signs and the long-term prognosis of patients with ischaemic stroke who have received intravenous thrombolysis.^10–14 This prospective, multicentre, observational study aimed to investigate the effectiveness and safety of wearable intelligent vital sign monitoring devices in the early in-hospital management and monitoring programme for patients with AIS.

Methods and design

Objective

1. Evaluate the effectiveness and safety of an in-hospital treatment and monitoring programme for ultra-early AIS based on intelligent wearable vital sign monitoring devices.

2. Explore the relationship between changes in ultra-early AIS vital signs and disease prognosis.

Study design

This prospective, multicentre, observational study will include 10 tertiary hospitals in China. Patients will be prospectively recruited from 20 March 2023 to 20 March 2025.

Study participants

Inclusion criteria

1. Age older than 18.

2. Diagnosed with AIS.

3. Within 4.5 hours from clinical symptom onset.

4. Received intravenous rt-PA.

5. Each participant or representative provided written informed consent.

Exclusion criteria

1. Uncooperative participants during follow-up.

2. Participants who have not completed intravenous thrombolysis.

3. Participants received bridging therapy or direct endovascular thrombectomy.

4. Participants who were admitted to our hospital after intravenous thrombolysis in other hospitals.

5. Participants with a life expectancy ≤6 months.

6. Participants who have participated in other clinical trials.

Outcome measures

Primary outcome

1. The proportion of mRS 0–1 at 90 days.

2. Rate of symptomatic intracranial haemorrhage during hospitalisation.

3. Rate of asymptomatic intracranial haemorrhage during hospitalisation.

Secondary outcome

1. Readmission at 30 days (±3 days) after discharge.

2. The distribution of mRS at 90 days (±14 days) and 1 year (±1 month) was 0–6 points.

3. Recurrent stroke events at 30 days (±7 days), 90 days (±14 days) and 1 year (±1 month).

4. Cardiovascular events at 30 days (±7 days), 90 days (±14 days) and 1 year (±1 month).

5. All-cause deaths occurred at 30 days (±7 days), 90 days (±14 days) and 1 year (±1 month).

6. Nursing Activities Score and self-designed Technology Acceptance Scale.

Determination of sample size

The sample size was calculated based on mRS obtained from previous studies.^13–15 According to favourable neurological outcomes (mRS 0–1) in patients who received intravenous thrombolytic therapy under the conventional clinical monitoring mode, the target value was not less than 50%. On the assumption that the target value of 55% favourable prognosis (mRS 0–1) at 90 days in patients who received intravenous thrombolytic therapy for vital signs monitoring with wearable monitoring devices. This study estimated the number of samples according to the sample content estimation formula designed in the cohort study. To compensate for potential dropouts (assumed dropout rate: 10%), the total samples are about 2870 cases in each group, and a total of 5740 observation samples are required in both groups.

Subject grouping

Participants will be enrolled in the conventional monitoring group from 20 March,2023 to 20 March, 2024 and the wearable monitoring group from 21 March, 2024 to 20 March, 2025.

Wearable vital sign monitoring devices

The WisMed (HPMS109) wearable monitor enables healthcare professionals to manage patients’ vital signs while they are active or in remote monitoring settings. This wearable monitor was validated by the Heilongjiang Provincial Drug Administration (No. 20192070038). WisMed (HPMS109) is a wearable, arm-mounted device that monitors blood pressure, ECG, pulse rate, oxygen saturation and respiratory rate. On the basis of guideline requirements and previous development by the team, the wearable monitor monitored blood pressure at prespecified frequencies every 15 min for 1 hour from the start of alteplase therapy, every 15 min for 2 hours from the end of alteplase therapy, followed by every 30 min for 6 hours and then every hour for 16 hours.

Conventional vital signs monitoring devices

Participants in the conventional monitoring group use conventional vital signs monitoring devices for blood pressure, ECG, pulse rate, oxygen saturation and respiratory rate. In this group, vital signs will also be monitored according to guidelines, while monitoring devices cannot be moved with the participant and the frequency of monitoring has to be adjusted manually. In addition, neurological assessments will be performed in accordance with guidelines, regardless of the assigned groups.

Training

Uniform training will be provided to the doctors and nurses who participated in this study. The training was supervised by the organiser and conducted at Xuanwu Hospital, Capital Medical University, China. The following standard operating procedures (figure 1) should be followed if wearable intelligent vital signs monitoring devices are used to monitor the intravenous thrombolysis process and post-thrombolysis monitoring of patients with AIS, while the following standard operating procedures (figure 2) should be followed in the conventional monitoring device group.

Figure 1.

Standard procedure for wearable vital signs monitoring group.

Figure 2.

Standard procedure for conventional vital signs monitoring group.

Data collection

We have established a complete and standardised Clinical Research Form (CRF) and developed the Electronic Data Capture System (EDC) based on the standard CRF (http://study.ericure.com/login). The trained Clinical Research Coordinator of each participating centre will collect the contents of the CRF from medical records and then upload them to the EDC system. The data will be mainly recorded in the electronic database. The Clinical Research Associate will supervise the electronic database.

The follow-up data in this study will be centralised and implemented by Xuanwu Hospital, Capital Medical University. Assessments during follow-up periods will be conducted at baseline, 24–48 hours after thrombolytic therapy, at discharge 30 days (±7 days) after intravenous thrombolysis, 30 days (±3 days) after discharge, 90 days (±14 days) after intravenous thrombolysis and 1 year (±1 month) after intravenous thrombolysis. The study schedule of assessments is shown in table 1.

Table 1.

Main variables registered in this study

Follow-up	The baseline (first clinical data entry after admission)	24–48 hours after thrombolytic therapy	At discharge	30 days (±7 days) after intravenous thrombolysis	30 days (±3 days) after discharge	90 days (±14 days) after intravenous thrombolysis	1 year (±1 month) after intravenous thrombolysis
Timing	Visit 1	Visit 2	Visit 3	Visit 4	Visit 5	Visit 6	Visit 7
Method of follow-up	Face-to-face	Face-to-face	Face-to-face	Telephone follow-up	Telephone follow-up	Telephone follow-up	Telephone follow-up
Informed consent	×
Inclusion/exclusion criteria	×
Demographic data*	×
Medical history†	×
Medication history‡	×
Family history§	×
Baseline information¶	×
Information on intravenous thrombolytic therapy**	×
Information after intravenous thrombolytic therapy††		×	×
Laboratory examination and imaging examination‡‡	×	×	×
Wearable intelligent monitor information§§		×	×
Discharge information¶¶			×
Neural function recovery***			×			×	×
Stroke recurrence†††				×		×	×
Cardiovascular events‡‡‡				×		×	×
Readmission to hospital§§§					×
All-cause mortality¶¶¶				×		×	×

*Patients’ demographics: age, sex, height and weight.

†Medical history: stroke, hypertension, hyperlipidaemia, atrial fibrillation, coronary heart disease and diabetes.

‡ Medication history: history of antiplatelet drugs, history of lipid-lowering drugs and history of antihypertensive drugs.

§Family history: history of cerebrovascular and cardiovascular diseases.

¶ Baseline data: duration from onset to admission, duration from onset to treatment, duration from admission to thrombolysis, admission diagnosis, infarct site, mRS, NIHSS, laboratory examination (routine blood test, blood biochemistry, coagulation function test and blood glucose), Imaging examination (CT of the head, Alberta Stroke Programme Early CT Score, brain MRI), UK National Early Warning Score.

**Information in intravenous thrombolytic therapy: types of thrombolytic drugs, dose of thrombolytic drugs, application and dose of antihypertensive drugs during thrombolytic therapy.

††Information after intravenous thrombolytic therapy: application of antiplatelet drugs and antihypertensive drugs after thrombolytic therapy, NIHSS score 24 hours after thrombolytic therapy, mRS after thrombolytic therapy, cerebral haemorrhage transformation after intravenous thrombolytic therapy, neurological deterioration after intravenous thrombolytic therapy, stroke recurrence, cardiovascular events and all-cause death.

‡‡Laboratory examination and imaging examination: laboratory examinations (routine blood test, blood biochemistry, coagulation function test), imaging data (brain CT, brain MRI, transcranial Doppler ultrasound and vascular ultrasound).

§§Vital signs during hospitalisation: blood pressure (systolic/diastolic blood pressure), heart rhythm, heart rate, breathing, oxygen saturation collected by wearable intelligent vital signs monitoring device/conventional multiparameter vital signs monitors.

¶¶ Discharge data: TOAST classification, mRS, NIHSS, Barthel Index and discharge diagnosis.

***Neural function recovery: mRS.

†††Stroke recurrence: The patient was diagnosed with an ischaemic or haemorrhagic stroke for the first time and received systematic treatment. Twenty-four hours after the original neurological defect symptoms and signs were reduced or improved, new neurological impairment symptoms or signs appeared and new lesions were confirmed by head CT or MRI.

‡‡‡Cardiovascular events: composition of non-fatal stroke, non-fatal myocardial infarction and death from cardiovascular causes.

§§§Readmission: rehospitalised after discharge.

¶¶¶All-cause mortality: deaths due to any cause other than unintentional injury during the follow-up period.

mRS, modified Rankin Scale; NIHSS, National Institute of Health Stroke Scale; TOAST, Trial of Org 10172 in Acute Stroke Treatment .

Statistical analysis

The data will be analysed by using SPSS 25.0. If the patient refuses to participate in the study or cannot be contacted after three telephone contacts within 1 week, it will be considered a dropout. Multiple imputations will be used to fill in the missing variables.¹⁶ For continuous variables with normal distribution, it will be expressed as ${\displaystyle \overline{\chi }\pm s}$; for non-normal data, it will be expressed as M (P₂₅∼P₇₅); for count data and ranked data, it will be expressed as cases (n) and rate (%). A parametric test (one-way analysis of variance, t-test) or non-parametric test will be used for intergroup comparison. A t-test or rank sum test will be used for continuous variables, a χ² test or Fisher’s exact test will be used for dichotomous variables and continuous variables will be compared using a Student’s t-test or Mann-Whitney U test, depending on the distribution.

Ethics statements

Informed consent will be obtained from participants. Each participant or representative provided written informed consent. The patient can decide to withdraw from the study at any time. On study completion, all participants will receive their collected research data during this study.

Quality control

During the research process, clinical monitors will conduct on-site or online monitoring visits to the participating centres regularly, ensuring that the research protocol and the accuracy of data filling are strictly followed by all centres. All data and protocol execution/modification should be truly recorded and retained by each research centre. During recruitment, the consistency of inclusion criteria and exclusion criteria should be ensured. At the end of the research, all data and materials related to the study will be archived by Xuanwu Hospital, Capital Medical University.

Data sharing and dissemination

Data and results will be shared among authors, but the leading institution (the Xuanwu Hospital, Capital Medical University) will be responsible for data integrity and statistical analysis.

Patient and public involvement

There was no patient or public involvement in the development of the research question and outcome measures.

Discussion

In this prospective, observational, multicentre study, the standard treatment and nursing procedures for patients with AIS were used. Previous studies indicated that vital sign data, including blood pressure and heart rate variability, are associated with disease progression and prognosis in patients with AIS. However, continuous monitoring, data storage and analysis cannot be achieved using conventional monitoring methods. Therefore, both wearable intelligent vital signs monitoring devices and conventional monitoring devices will be used in this study in order to explore the characteristics of early continuous vital signs in patients with AIS and investigate the relationship between vital signs and disease prognosis. In addition, the safety and effectiveness of wearable vital sign monitoring devices in the early treatment of AIS will be measured.

Ethics statements

Patient consent for publication

Not applicable.