Researchers in the United Kingdom have released the first results from a multisite platform trial that examined three existing drugs for the treatment of fatigue that persists after acute COVID‑19 infection.
Trial design and medication choices
The study, part of the STIMULATE‑ICP consortium, recruited participants from specialized long COVID clinics and additional sites. All volunteers had symptoms lasting at least four weeks and no other identifiable cause, as confirmed by a specialist clinician.
Three drugs were selected based on prior laboratory and clinical hints of benefit: the anticoagulant rivaroxaban, the anti‑inflammatory colchicine, and a combination of the antihistamines famotidine and loratadine. The investigators argued that these agents might address reported abnormalities in clotting pathways, endothelial inflammation, and mast‑cell activity linked to post‑COVID conditions.
Participants were assigned to one of four arms: rivaroxaban 10 mg daily (197 patients), colchicine 500 µg twice daily (192 patients), famotidine 40 mg plus loratadine 10 mg daily (193 patients), or usual integrated care without trial medication (196 patients). The trial remained open‑label and pragmatic, meaning that all patients continued to receive standard long COVID care throughout the study.
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Fatigue outcomes at 12 and 24 weeks
The primary endpoint measured change in Fatigue Assessment Scale (FAS) scores after 12 weeks, with a secondary measurement at 24 weeks. Adjustments accounted for baseline fatigue levels and other relevant clinical variables.
At the 12‑week mark, the colchicine group showed a modest reduction in fatigue scores compared with the control group (‑1.49 points; 95 % CI ‑2.92 to ‑0.04). The famotidine‑loratadine arm produced a similar decline (‑1.48 points; 95 % CI ‑2.88 to ‑0.08). Rivaroxaban did not achieve a statistically significant difference.
By week 24, none of the medication groups displayed a clear advantage over usual care; all arms, including the control, reported some degree of fatigue improvement.
From a broader perspective, the trial illustrates the challenges of repurposing existing drugs for a condition as heterogeneous as long COVID. While the modest gains observed hint at possible mechanisms worth exploring, the lack of durable impact highlights the need for more targeted therapies that address the underlying pathophysiology rather than relying on broad anti‑inflammatory or anticoagulant effects alone.
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Implications and next steps
Study authors emphasized that the open‑label design was chosen to avoid delays associated with placebo manufacturing and to maintain trust among patients who often face stigma and barriers to care. They noted that only a small fraction of control participants inadvertently received trial medications (about 3 % for famotidine and loratadine, 1 % for colchicine).
Future research could focus on specific subgroups of long COVID sufferers or explore combination regimens, acknowledging that “long‑term long COVID symptom benefit is unlikely with these drugs alone.”
The trial’s results add to a growing body of evidence that while some repurposed agents may alleviate certain symptoms, full management of post‑COVID fatigue will likely require novel approaches tailored to individual patient profiles.