Cognitive Care Bundle for Ischaemic Stroke : A Pilot Randomised Controlled Trial

Study Design Overview

This is a single-centre, pilot prospective randomised open-label, blinded end-point (PROBE) controlled trial. The study aims to evaluate the feasibility, adherence, and preliminary efficacy of a multi-domain cognitive care bundle in preventing post-stroke cognitive impairment (PSCI) among patients with acute ischemic stroke.

Rationale

Post-stroke cognitive impairment affects up to 60% of stroke survivors within the first year and is associated with poorer functional outcomes, reduced rehabilitation potential, and increased long-term risk of dementia. Despite identification of several modifiable risk factors-including hypertension, hyperglycaemia, malnutrition, sensory impairments (visual and hearing loss), and post-stroke depression-there is limited real-world evidence that systematic optimisation of these factors improves cognitive outcomes. This study will test a bundled intervention targeting these modifiable domains.

Study Setting

The trial will be conducted at Hospital Canselor Tuanku Muhriz (HCTM), Universiti Kebangsaan Malaysia, a tertiary academic medical centre. Recruitment will occur from the acute stroke ward and neurology clinic.

Participant Timeline

Screening and enrolment: Within 7 days of ischemic stroke onset

Baseline assessment: Montreal Cognitive Assessment (MoCA), Ascertain Dementia 8 (AD-8), Hospital Anxiety and Depression Scale (HADS), modified Rankin Scale (mRS), and EQ-5D-5L

Intervention period: From hospital discharge to 3 months post-stroke

Follow-up assessment: At 3 months post-stroke (primary timepoint), conducted by a blinded rater

Intervention Description

Participants randomised to the intervention arm will receive standard medical therapy plus a cognitive care bundle consisting of six components:

Home blood pressure (BP) monitoring: Daily BP measurement using a provided home device, with target BP <130/80 mmHg. Readings recorded on a standardised logsheet. Weekly teleconsultation with the study investigator; if ≥3 of 7 readings are above target, antihypertensive medication adjustment will be considered (prescriptions issued as needed).

Home blood glucose monitoring (for participants with diabetes mellitus): Daily fasting and random capillary glucose measurement using a provided glucometer. Target ranges: fasting 4.4-7.0 mmol/L, random 4.4-8.5 mmol/L. Weekly review during teleconsultation; medication adjustment if ≥3 of 7 readings are out of range.

Dietitian referral: All intervention participants receive a referral to a clinical dietitian for comprehensive nutritional assessment, individualised dietary advice, and optimisation of feeding regimes (including for those with dysphagia or enteral tube feeding). Nutritional deficiencies will be screened and managed.

Vision screening: Bedside assessment using Snellen chart and confrontational visual field testing by the research team. Participants with detected visual impairment will be referred to the ophthalmology clinic for formal evaluation and management.

Hearing assessment: Referral to audiology for formal hearing evaluation using pure-tone audiometry. Appropriate management (e.g., hearing aids) will be arranged as indicated.

Depression screening: Administration of the Hospital Anxiety and Depression Scale (HADS) prior to discharge. Participants with HADS-depression subscore ≥8 (indicating probable depression) will be referred to psychiatrist or psychological services for further assessment and treatment.

Control Arm

Participants in the control arm will receive standard medical therapy as per local clinical practice guidelines. This includes routine blood pressure and glucose monitoring (in clinic), physiotherapy referral, dietitian referral only for nasogastric tube-fed patients, risk factor screening, and cognitive screening with referral to cognitive therapy if clinically indicated. No weekly teleconsultation or proactive home monitoring is provided.

Randomisation and Blinding

Eligible participants will be randomised 1:1 to intervention or control using a blocked randomisation list (block size variable, concealed). Stratification factors: age (≥65 years vs. <65 years) and baseline MoCA score (18-21 vs. 22-25). The randomisation sequence will be generated using Sealed Envelope (https://www.sealedenvelope.com) and kept by an independent person not involved in enrolment or outcome assessment.

The study is open-label for participants and investigators delivering the intervention. However, outcome assessors at 3 months will be blinded to treatment allocation. The primary analyses will be conducted on an intention-to-treat basis.

Data Collection and Management

Data will be collected using standardised case report forms (CRFs) at baseline and 3 months. Source documents include medical records, participant-completed logs (BP and glucose), teleconsultation records, and specialist referral outcomes. Hard-copy CRFs will be stored in locked cabinets; data will be entered into SPSS (Version 29.0) with password-encrypted files. Participant identities will be coded and not traceable in the analytical dataset.

Feasibility Outcomes (Primary)

Feasibility will be assessed by:

Adherence rate to the cognitive care bundle (proportion of participants completing ≥80% of scheduled weekly teleconsultations and home monitoring logs)

Proportion of participants requiring medication adjustments during weekly reviews

Proportion of participants successfully referred to and attending dietitian, ophthalmology, audiology, and psychiatry/psychology services

Clinical Outcomes (Secondary)

Cognitive function: MoCA score (range 0-30, higher better) and AD-8 score (range 0-8, score ≥2 indicates cognitive impairment) at 3 months

BP control (systolic and diastolic BP at 3 months)

Glycaemic control (HbA1c at 3 months)

Functional status: modified Rankin Scale (mRS) at 3 months

Mood: HADS score (anxiety and depression subscores) at 3 months

Quality of life: EQ-5D-5L index value and visual analogue scale (VAS) at 3 months

Sample Size Justification

Based on Whitehead et al. (2016) and Teresi et al. recommendations for pilot feasibility studies, a sample size of 25 participants per arm (total N=50) is adequate to estimate feasibility parameters and provide a small effect size (standardised effect size 0.2) for preliminary efficacy. This sample size is appropriate for a pilot trial designed to inform a future definitive randomised controlled trial.

Statistical Analysis Plan

Descriptive statistics will be used to summarise baseline characteristics and feasibility outcomes. Categorical variables presented as frequencies (percentages); continuous variables as mean (SD) or median (IQR) based on normality. Between-group comparisons at 3 months will be performed using:

Chi-square test (or Fisher's exact) for binary outcomes (e.g., proportion with MoCA <26)

Independent t-test (or Mann-Whitney U test) for continuous outcomes (MoCA, HbA1c, BP, HADS, EQ-5D-5L)

Ordinal logistic regression for mRS (ordinal outcome)

Multivariable regression will adjust for prespecified confounders (age, baseline MoCA, and any baseline variable with p<0.10 on univariate analysis). Two-tailed p<0.05 will be considered statistically significant. All analyses will be performed using SPSS Version 29.0.

Data Monitoring

Periodic data monitoring will be conducted by a researcher independent of the study team to verify that CRF data match source documents. Given the low-risk nature of the intervention (behavioural and monitoring interventions with no investigational drug or device), no independent Data Safety Monitoring Board (DSMB) is planned. Serious adverse events will be reported to the Principal Investigator within 24 hours and to the UKM Research Ethics Committee as per institutional policy.

Ethics and Dissemination

The study has received approval from the Universiti Kebangsaan Malaysia Research Ethics Committee (approval number to be JEP-2026-144). Written informed consent will be obtained from all participants or their legal guardians.