"Nature Medicine asks leading researchers to name their top clinical trial for 2026, from long-awaited vaccines for infectious diseases to new treatments for advanced cancers and long COVID."
Anyone have access to see what they say for long COVID?
"Nature Medicine asks leading researchers to name their top clinical trial for 2026, from long-awaited vaccines for infectious diseases to new treatments for advanced cancers and long COVID."
Anyone have access to see what they say for long COVID?
Emma Wall: I am an infectious disease physician and research scientist at University College Hospital in London and the Francis Crick Institute. During the pandemic, I was working both in acute-COVID care and in a long-COVID clinic with respiratory colleagues. We were seeing many patients with extreme fatigue, and we talked about which, if any, drugs we should use, but decided instead to do a trial. We joined forces with others and were awarded £6.8 million funding from the National Institute for Health and Care Research, which is like the UK’s version of the National Institutes of Health (NIH), to run a major trial testing drugs and other interventions for long COVID [1].
We designed the trial in 2021, when we still knew very little about long COVID. Most of our patients had debilitating fatigue, especially something called post-exertional malaise — basically, when any effort makes people feel like they have run a marathon. We found that even short walks caused abnormal blood changes, suggesting problems in tiny blood vessels. So, we tested drugs in the trial that might reduce inflammation or improve blood flow, including an anticoagulant and anti-inflammatory options.
It has been heartbreaking — many patients were previously healthy young professionals who have been ill for years. We involved patients directly in designing and running the trial, including drug selection and shaping the study design, making it open label because they wanted transparency. The trial is complete, the analysis finished and the manuscript has been submitted — we are planning to present the results later this year in Boston and publish them in 2026.
Emma Wall is a clinical research group leader at the Crick and consultant in infectious diseases at University College London Hospitals, London, UK.
If anyone's interested, here's a 51 minute talk from Emma Wall from earlier this year:
00:00 Intro
02:54 What is long COVID?
07:48 A patient's perspective
10:30 Who can be affected?
13:50 What is the cause?
19:06 Symptoms
23:43 Can it be prevented?
27:44 Treatment
33:07 What's being done?
36:18 Studies and trials
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...
journals.plos.org
An explanation of why these drugs were chosen is available here:
STIMULATE-ICP (Symptoms, Trajectory, Inequalities and Management: Understanding Long COVID to Address and Transform Existing Integrated Care Pathways) NIHR Long COVID trial. UCLH Study.
www.stimulate-icp.org
Why have these drugs been chosen?
Long COVID is a new disease and the underlying mechanisms are still being investigated and understood. Therefore, we do not yet know which drugs will work. That is why we need to do trials to assess whether these drugs are useful and effective for patients. First, the drugs we have chosen are widely available and some health professionals and patients have reported that they may be useful. Second, there is a plausible mechanism by which these drugs might work in long COVID. Third, these drugs are already available for use in other conditions, and so could be relatively easily “repurposed” at scale to treat long COVID, if they were shown to be effective in a trial.
Famotidine/Loratidine: Patients with long COVID may have persistent inflammation, which is related to “mast cell activation” and release of histamine. Famotidine and loratadine are histamine receptor blockers which are commonly used to treat mast-cell activation in other conditions. In long COVID, antihistamines have been of benefit in some patients.
Rivaroxaban: People with long COVID may have “micro-clots” in their circulation. These clots could reduce oxygen reaching large muscles during exercise, possibly explaining the “post-exertional malaise” which people with long COVID often describe. There are increasing reports from patients and their health professionals of success of therapy with anti-clotting drugs such as rivaroxaban.
Colchicine: In some patients with long COVID, there is inflammation around the lining of the heart (“pericarditis”) and lungs (“pleuritis”). Colchicine is an anti-inflammatory drug which has benefit in pericarditis. Given the high proportion of people with long COVID who have chest pain and breathlessness, pericarditis and pleuritis are likely to be common, and colchicine may be of benefit.
There is potentially scope for other drugs to be added to the trial platform via the COVID Therapeutic Taskforce.
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...
journals.plos.org
An explanation of why these drugs were chosen is available here:
STIMULATE-ICP (Symptoms, Trajectory, Inequalities and Management: Understanding Long COVID to Address and Transform Existing Integrated Care Pathways) NIHR Long COVID trial. UCLH Study.
It is insane to me this trial has taken what - four years? Without adding other drugs. These are very basic drugs, and if they help pwLC we should have had that info years ago and moved on. There should be a Stimulate ICP anti cd38 or even JAK inhibitor trial in the works. There should have been so much more basic research into LC and ME/CFS funded. The government's refusal to fund any new long covid research for years, including Danny Altmann's stuff, is absolutely unforgivable and will go down in history as a cynicial and hubristic refusual to engage in any way with one of the biggest health issues facing society. It shows just how poorly equipped the politcal class, regardless of party, are to deal with emerging public health crises.
There is also already a trial of Colchicine for LC, which found null results:
Conclusions and Relevance In this randomized clinical trial, among adults with long COVID, colchicine did not improve functional capacity, respiratory function, or inflammatory markers. These findings underscore the need to explore alternative therapeutic approaches for long COVID.
Full title: STIMULATE-ICP-Delphi (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways Delphi): Study protocol
Abstract
Introduction
As mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in...
Full title: STIMULATE-ICP-CAREINEQUAL (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways) study protocol: Defining usual care and examining inequalities in Long Covid support
Abstract
Introduction
Individuals with Long Covid represent a new and growing patient population. In England, fewer than 90 Long Covid clinics deliver assessment and treatment informed by NICE guidelines. However, a paucity of clinical trials or longitudinal cohort studies means that the epidemiology...
This BPS-focused questionnaire is open to everyone with a long-term chronic illness. Its explicit aim is to build support for a BPS approach to LC. You know what to do: answer honestly. It's short, about 5-10 minutes.
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
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.
Why on earth was the trial open label?
Presumably it didn't show anything, otherwise we would have heard.
The rationales are cringemakingly simplistic.
This is just the sort of thing people might get from a 'Centre of Excellence Hub' for ME/CFS. Be careful what you wish for.
The more useful aspects of this study will be the proteomics, eg TGF-beta, cell motility, extracellular vesicles and platelet activation.
The drug therapies probably won't shed too much light. As above, colchicine wasn't going to be useful (I think I recall them saying they chose it before they really had much idea what was going on in LC). Low dose Rivaroxiban is also unlikely to have ever been able to do much either (±homeopathic because they were worried about side effects in a cohort with many menstruating women). Famotidine/larotodine gave some modest signal on-drug / off-drug — but as noted this was open-label with questionnaires.
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