Treatment with colchicine and famotidine plus loratadine, in addition to specialist supportive care, can substantially ease severe fatigue among patients suffering from long COVID, as shown by the results of the STIMULATE ICP trial.

“In individuals with long COVID, severe fatigue reduces with specialist supportive care and may further be reduced by colchicine and famotidine/loratadine,” said study co-author and presenter Dr Emma Wall, from the Francis Crick Institute, London, UK, and the National Institute for Health Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.

STIMULATE ICP is a phase 3, four-arm randomized controlled, open-label trial conducted across 12 UK NHS specialist long COVID clinics. Wall and her team randomly allocated a total of 778 adults to receive colchicine 500 mcg BD, rivaroxaban 10 mg OD, famotidine 40 mg OD with loratadine 10 mg OD, or no drug for 12 weeks.

Fatigue, the primary endpoint, was measured using the Fatigue Assessment Scale (FAS) score, ranging from 10 (no fatigue) to 50 (debilitating fatigue). Other endpoints assessed included quality of life, measured using the EuroQol Visual Analogue Scale (EQ-VAS) at 12 and 24 weeks and FAS at 24 weeks.

Of the adult patients with long COVID (mean age 46 years), 495 were female (63.6 percent), and 91 (11.9 percent) were from a UK minority ethnic group. High FAS (mean 36.8) at baseline hinted at “equivalent and severe fatigue” across groups. [ESCMID Global 2026, abstract L0020]

Reduced fatigue

At 12 weeks, all treatment groups showed improvements in fatigue, with an overall reported reduction of 4.3 points to 32.5 in mean FAS across trial arms.

Furthermore, slight decreases in FAS were seen among participants who received both colchicine and famotidine with loratadine relative to those assigned to the on-drug arm, but not to the rivaroxaban arm (colchicine: -1.49 points, 95 percent confidence interval [CI], -2.92 to -0.06; p=0.041; famotidine plus loratadine: -1.48 points, 95 percent CI, -2.87 to -0.08; p=0.038; rivaroxaban: -1.06 points, 95 percent CI, -2.47 to 0.34; p=0.139).

After correcting for symptom duration, participants who received rivaroxaban reported a change in FAS of -1.71 points (95 percent CI, -3.15 to -0.27; p=0.020).

In terms of quality of life, all treatment arms demonstrated a small but significant improvement in EQ-VAS when compared to the no-drug arm. However, 12 weeks following treatment cessation, FAS was equivalent between groups at 24 weeks.

“Quality of life was marginally improved in all drug arms, but additional observed effects on either FAS or EQ-VAS were not sustained after drug withdrawal,” Wall said.

Long COVID continues to have a substantial impact on individuals and health systems, with nearly 2 million people estimated to suffer from it in the UK and major long-term effects on healthcare utilization. [Nat Commun 2022;13:3528; J R Soc Med 2024;117:369-381; BMC Med 2024;22:255]

Moreover, definitions of long COVID are vague, and diagnostic tests are lacking. The trajectory of the disease is also poorly defined, with only a few clinical trials investigating the condition. Currently, no high-quality evidence base exists for therapeutic effectiveness, according to a related study. [BMJ 2024;387:e081318; BMJ Open 2026;16:e103884]

Fatigue, including postexertional malaise, is the most common symptom of long COVID, “but data to support treatment, including the use of repurposed medications, are limited,” Wall said.