Efficacy and safety of rivaroxaban, colchicine, and famotidine–loratadine with specialist supportive clinical care for fatigue..., 2026, STIMULATE-ICP

[Dolphin]

Commonly used drugs show small benefit for long Covid fatigue

Over-the-counter antihistamines and a prescription anti-inflammatory drug both have a small benefit in reducing long Covid fatigue among people receiving care from specialist long Covid clinics, according to new findings from a large clinical trial led by UCL (University College London) and UCLH.

www.eurekalert.org

News Release 8-Jul-2026

Commonly used drugs show small benefit for long Covid fatigue​

Peer-Reviewed Publication
University College London


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Over-the-counter antihistamines and a prescription anti-inflammatory drug both have a small benefit in reducing long Covid fatigue among people receiving care from specialist long Covid clinics, according to new findings from a large clinical trial led by UCL and UCLH.

The study, published in The Lancet Infectious Diseases journal and funded by the National Institute for Health and Care Research (NIHR), involved nearly 800 adults in England with long Covid who were randomly assigned either usual care or one of three types of drugs: a combination of antihistamines (allergy medicines), an anti-inflammatory drug called colchicine (used to treat gout), or a blood thinner called rivaroxaban (typically used to prevent blood clots and strokes).

The research team found that all groups experienced a meaningful reduction in their self-reported fatigue over 12 weeks (improving an average of 4.3 points on a 40-point scale), supporting the idea that specialist long Covid care can lead to important improvements in symptoms.

Those taking antihistamines and colchicine, but not the blood thinner rivaroxaban, saw a small additional benefit in fatigue reduction at 12 weeks (an extra 1.5 point improvement on the scale). However, this benefit was not sustained at 24 weeks (12 weeks after the participants stopped taking the drugs).

The trial was conducted by a national team of researchers, clinicians and patients across 12 clinics in England and Scotland led by co-chief investigators Professor Amitava Banerjee at UCL and Dr Melissa Heightman at UCLH. More than 30 organisations were involved, with UCLH recruiting around half the patients on this trial and the University of Lancashire Clinical Trials Unit co-ordinating all of the recruiting sites.

Professor Banerjee (UCL Institute of Health Informatics), the corresponding author, said: “We tested potential medicines based on the most promising theories of how to improve long Covid when we started out in 2021. Our findings suggest these drugs alone are unlikely to be the answer to long Covid fatigue. Antihistamines and the anti-inflammatory drug, colchicine, did provide a small benefit, but this did not last once participants stopped taking them and so they are unlikely to improve symptoms over the long term on their own.

“Both antihistamines and colchicine affect the immune system and it may be that they address the immune dysregulation that long Covid has been linked to, but further research is needed to understand the possible mechanism.

“The blood thinner, rivaroxaban, had no benefit and so our results do not support the use of anti-coagulation medicine for long Covid.”

Dr Melissa Heightman, clinical lead for the post-Covid service at UCLH, said: “It is heartening that people had a significant reduction in fatigue across all arms of the trial. This is more than you would expect based on time alone, given that participants had severe fatigue at recruitment and been ill for more than a year on average.

“This level of improvement shows the importance of specialist long Covid care. These services in England offer integrated care from a range of specialties with community-based rehabilitation to develop a plan for a person based on their symptoms and all of the ways the condition affects them.”

Participants of the trial were adults with long Covid who had not been hospitalised. The 12 long Covid clinics ranged from Hull and the Highlands to Leicester and London. Fatigue was assessed with a questionnaire at the start of the trial and then after 12 and 24 weeks.

The trial was open-label, meaning participants knew which drug they were taking (there was no placebo in the non-drug group), and so the researchers were unable to rule out a placebo effect. However, they said the benefit seen in two of the drug groups was unlikely to be caused by placebo alone, given that no such benefit was found for the other drug group (rivaroxaban).

Professor Banerjee said: “We have shown it is possible to conduct a large clinical trial for long Covid and to test treatments as we would for any other condition.”

Professor Danny McAuley, Scientific Director for NIHR Programmes, said: "The NIHR is proud to have funded this vital trial, which highlights the value of specialist care in delivering meaningful relief for long Covid patients. Finding even modest benefits for these inexpensive drugs, which are safe and commonly used for other conditions, is incredibly important to improve the evidence-based treatment of this complex condition. By providing the high-quality data needed to refine clinical approaches, this research ensures that the NIHR is helping to build a clearer, safer path forward for patient care which can be provided in the community."

Professor Emma Wall, Clinical Research Group Leader at the Crick, Professor of Infectious Diseases at Queen Mary University of London, and academic consultant in Infectious Diseases and Acute Medicine for UCLH, said: "Because long Covid is such a new and complex condition, when it came to designing the trial, we started by listening to what patients were telling us about their symptoms and experiences, then looking for biological signals that might explain them and treatments that might help.

"The value of these results is not only that they suggest a potential treatment approach, but that they help us understand the biology of long Covid itself. Every signal we see in the trial helps us refine our understanding of the immune and inflammatory mechanisms that may be driving the disease, to develop new, better targeted treatments for future trials.”

---

Journal​

The Lancet Infectious Diseases

 

[Jonathan Edwards]

Dr Melissa Heightman, clinical lead for the post-Covid service at UCLH, said: “It is heartening that people had a significant reduction in fatigue across all arms of the trial. This is more than you would expect based on time alone, given that participants had severe fatigue at recruitment and been ill for more than a year on average.

With an open trial and a subjective outcome measures I do not think you can say that. Graham's PACE trial video points out why. Given all the contextual factors I think the result is absolutely what one would expect if none of the treatments had any specific useful action.

 

[Utsikt]

Wow, this is bad. It’s like they’ve decided beforehand on what to do, and then asked an LLM to give them a list of reasons for why they should do it that way.

We did a phase 3, four-group, randomised, controlled, adaptive platform, open-label drug trial nested within a pragmatic, multicentre, cluster-randomised trial of an integrated care pathway (ICP) for long COVID across 12 UK National Health Service (NHS) specialist long COVID care clinics in the UK.

That’s a mouthful.

Across all trial groups, there was severe baseline fatigue (mean FAS score 36·8 [SD 7·49]) and a clinically relevant mean FAS reduction of 4·3 points to 32·5 (SD 9·13) at 12 weeks.

So the in-group changes were «clinically significant»…

Adjusted analyses showed small, statistically significant FAS reductions in the colchicine (–1·49 points [95% CI –2·92 to –0·06], p=0·041) and famotidine–loratadine (–1·48 points [–2·88 to –0·08], p=0·038) groups, but not in the rivaroxaban group (–1·06 points [–2·47 to 0·35, p=0·139), compared with no study drug at 12 weeks. However, 24-week FAS scores, 12 weeks after drug cessation, were not significantly different between groups.

…but the between-group differences were only statistically significant.

Here's the fatigue graph from main paper:

View attachment 33160

That’s straight out of the textbook on how to lie with graphs. Why on earth would they crop the y-axis?

I don’t even understand the scale on the y-axis. They say FAS ranges from 10-50, but the labels says 0-40. Have they transformed the values so 40 means 50, or does 40 actually mean 40 on the 10-50 scale? And how far off are they from the 20 of normal fatigue - is that really at 10? Why not show that as a line to demonstrate how absurdly little difference the interventions made and how much the participants are still affected by fatigue?

We chose an open-label design in this publicly funded trial, supported by the funder, our PPIE team, and ethical committee, with two aims: (1) to avoid estimated delays of 1 year and excessive costs (estimated £1 million) of developing placebo controls matched across all trial arms; and (2) to retain the trust of our patient population, many of whom experienced substantial stigma and barriers to care, reducing their trust in researchers and clinicians

1) we chose to waste all of the time and money instead of spending a bit more to ensure none was wasted.

2) uhm, what? How would include a placebo erode trust?

Professor Banerjee said: “We have shown it is possible to conduct a large clinical trial for long Covid and to test treatments as we would for any other condition.”

Evidently you have not because we normally use controlled trials. But LC patients are snowflakes that can’t handle potentially getting a placebo after providing informed consent to potentially getting placebo, and we can’t be bothering spending the resources to do it properly.

However, they said the benefit seen in two of the drug groups was unlikely to be caused by placebo alone, given that no such benefit was found for the other drug group (rivaroxaban).

That assumes all expectations were equal for the different drugs.

 

[ME/CFS Science Blog]

With an open trial and a subjective outcome measures I do not think you can say that. Graham's PACE trial video points out why.

In addition, the treatment effects were not clinically significant from what I can see.

They defined the minimally clinically important difference (MCID) for the primary outcome (the FAS) as a change of 3 points.

The FAS benefits compared to no treatment were :

-1.49 points [95% CI –2·92 to –0·06] for colchicine
-1·48 points [95% CI –2·88 to –0·08] for famotidine–loratadine.

So in both cases, there's clear evidence that the effect is not clinically significant.

 

[Hutan]

News Release 8-Jul-2026

Commonly used drugs show small benefit for long Covid fatigue​

That's as bad a press release as I have seen, in terms of spreading misinformation. It had me spluttering into my morning cup of tea. I kept quoting bits that were egregiously bad to comment on, and found that I had quoted virtually all of it.

Over-the-counter antihistamines and a prescription anti-inflammatory drug both have a small benefit in reducing long Covid fatigue among people receiving care from specialist long Covid clinics, according to new findings from a large clinical trial led by UCL and UCLH.

Wrong. The charts show that.

The research team found that all groups experienced a meaningful reduction in their self-reported fatigue over 12 weeks (improving an average of 4.3 points on a 40-point scale), supporting the idea that specialist long Covid care can lead to important improvements in symptoms.

Wrong. It says nothing at all about the benefits or otherwise of specialist Long Covid care.

Dr Melissa Heightman, clinical lead for the post-Covid service at UCLH, said: “It is heartening that people had a significant reduction in fatigue across all arms of the trial. This is more than you would expect based on time alone, given that participants had severe fatigue at recruitment and been ill for more than a year on average.

Dr Melissa Heightman and everyone associated with that press release should be embarrassed because it is clear that they do not understand the impact of subjective outcomes in unblinded trials.

“This level of improvement shows the importance of specialist long Covid care. These services in England offer integrated care from a range of specialties with community-based rehabilitation to develop a plan for a person based on their symptoms and all of the ways the condition affects them.”

splutter

Professor Banerjee said: “We have shown it is possible to conduct a large clinical trial for long Covid and to test treatments as we would for any other condition.”

What a strange statement from Professor Banerjee. No, if it was any other condition, you would probably do a proper blinded study when assessing the value of drugs.

Professor Danny McAuley, Scientific Director for NIHR Programmes, said: "The NIHR is proud to have funded this vital trial, which highlights the value of specialist care in delivering meaningful relief for long Covid patients. Finding even modest benefits for these inexpensive drugs, which are safe and commonly used for other conditions, is incredibly important to improve the evidence-based treatment of this complex condition. By providing the high-quality data needed to refine clinical approaches, this research ensures that the NIHR is helping to build a clearer, safer path forward for patient care which can be provided in the community."

The NIHR and Professor Danny McAuley should be embarrassed. There is clearly a political agenda here to support the idea of specialist clinics that teach people with Long Covid to 'have goals' and answer subjective questionnaires more positively, while giving them a placebo prescription of an anti-histamine or whatever else is cheap and fairly harmless.

I wonder when this data first became available - does it link in with the time when Garner et al started writing pieces about microclots?

 

[Hutan]

This makes me so furious. We have such an uphill job trying to convince patients to not waste money and effort and risk side effects on treatments that the evidence shows is ineffective.

And here, the people who, despite the amateurishness of the trial, have actually shown that several treatments are ineffective are spinning their results as showing the drugs are useful.

I think we might have to have an annual prize for 'most misleading but influential press release'. I would certainly nominate this one.

Letters need to be sent to everyone involved in running this trial.

 

[Jonathan Edwards]

I seem to remember saying a while ago that this is precisely what NIHR was set up to provide - politically convenient bogus answers. It is still disappointing.

 

[Chandelier]

Highland patients play key part in long Covid study

In a large clinical trial patients from the Highlands were the only ones in Scotland to take part.

www.inverness-courier.co.uk

Highland patients play key part in long Covid study​

Tiny 300-word article, ending on:

Dr Melissa Heightman, clinical lead for the post-Covid service at UCLH, said: “It is heartening that people had a significant reduction in fatigue across all arms of the trial. This is more than you would expect based on time alone, given that participants had severe fatigue at recruitment and been ill for more than a year on average.

“This level of improvement shows the importance of specialist long Covid care.”