STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol

Abstract

Introduction Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace. Methods and analysis This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as “standard of care” in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6–10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately. Ethics and dissemination The protocol was reviewed by South Central—Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations. Trial registration number ISRCTN10665760.

Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection

“…Early MRI assessment may identify organ-specific impairment (including cardiac), leading to early referral for appropriate specialist assessment and treatment, in contrast to the experience of many patients who are currently having multiple appointments with multiple specialists for multiple assessments. In a cluster-randomised design, the STIMULATE-ICP trial is currently evaluating whether multiorgan MRI (Coverscan) can aid diagnosis and follow-up of cardiac and multiorgan impairment in Long COVID, and reduce burden to healthcare systems, already struggling due to COVID-19-related lack of resources and backlogs, while achieving integrated care 29…”

Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder

“…Impaired exercise capacity such as in post-exertional malaise (PEM) has been reported to occur in 20% of patients, of which 18–55% was found to have indicators of a hypercoagulable state in lab tests [ 57 ]. Physical activity may worsen the condition of 75% of Long COVID patients and improves less than 1% [ 22 ], which suggests possible ongoing microvascular or endothelial dysfunction to play a role. Therefore, antithrombotic therapy might be considered in the treatment of these patients, which is currently evaluated in the ongoing STIMULATE-ICP trial [ 58 ].…”

“…A major new consortium of researchers, health professionals and patients are engaged in it to conduct a clinical trial evaluating integrated care and medication for Long COVID. Still in its recruitment phase, currently more than 500 patients have been recruited and are participating in the trial [ 22 ]. In addition, the STIMULATE-ICP-Delphi sub study seeks to answer the research question what are effective integrated care pathways for individuals with Long COVID and how can they be transferred to other long-term conditions [ 23 ].…”

What is current care for people with Long COVID in England? A qualitative interview study

“…The service manager and clinical lead for each of the six post-COVID-19 services, which were identified as part of a previous study, known as Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways, 26 were asked to review their database of people living with Long COVID, including those that may have signed up to take part in the research. Depending on the most appropriate site-specific means to approach people living with Long COVID, we contacted (via email, via an online Long COVID group at one site (led by the post-COVID-19 service) and/or via an internal hospital communication app at another site (MyCare application)) them to advertise the project and request their involvement.…”