Repurposed Drugs Show Modest, Short-Term Benefit for Long COVID Fatigue

A multisite, open-label, randomized controlled trial has found that the anti-inflammatory drug colchicine and a combination antihistamine regimen of famotidine and loratadine produced small, short-lived reductions in fatigue among adults with long COVID. However, the anticoagulant rivaroxaban showed no benefit at all.¹

The trial, led by University College London (UCL) and University College London Hospitals and funded by the National Institute for Health and Care Research (NIHR), enrolled nearly 800 adults with post-COVID-19 conditions across 12 specialist long COVID clinics in England and Scotland. Findings were published in The Lancet Infectious Diseases on July 8, 2026.¹

Trial Design and Key Findings

The trial, conducted through the STIMULATE-ICP consortium, randomly assigned nonhospitalized adults with long COVID to usual specialist care alone or to usual care plus 1 of 3 repurposed drug regimens: rivaroxaban, colchicine, or famotidine–loratadine. Fatigue was measured with a validated questionnaire on a 40-point scale at baseline and again at 12 and 24 weeks. Across all study groups, including the no-drug comparator, participants reported a meaningful reduction in fatigue over 12 weeks, improving by an average of 4.3 points, a finding the investigators attributed to the effect of specialist, multidisciplinary long COVID care itself rather than to any single drug.¹

Participants receiving colchicine or famotidine–loratadine saw a small additional benefit at 12 weeks, an extra 1.5-point improvement in fatigue score compared with usual care, but this benefit disappeared by 24 weeks, 12 weeks after participants stopped taking the study drugs. Rivaroxaban produced no measurable benefit over usual care at either time point. The trial was well tolerated, with 10 serious adverse events, unrelated to trial drugs, reported in 8 of 778 participants (1.0%), with 5 of these events occurring in 3 participants assigned to rivaroxaban.¹

Amitava Banerjee, MD, PhD, corresponding author and co-chief investigator at UCL's Institute of Health Informatics, said the trial tested drugs based on the leading mechanistic theories for long COVID when the study began in 2021.

"Our findings suggest these drugs alone are unlikely to be the answer to long Covid fatigue," Banerjee said in a news release.² He noted that colchicine and antihistamines both act on the immune system, which may explain their modest signal, though the underlying mechanism requires further study, and that the rivaroxaban results do not support using anticoagulation to treat long COVID fatigue.

Pharmacist Considerations for the Study Drugs

Rivaroxaban (Xarelto) is a factor Xa inhibitor approved for preventing and treating venous thromboembolism and for stroke prevention in atrial fibrillation, among other indications. It carries a well-established risk of serious, potentially life-threatening bleeding and numerous clinically significant drug interactions.³

Colchicine, marketed for gout and familial Mediterranean fever and, at low doses, for cardiovascular risk reduction in atherosclerosis, most commonly causes diarrhea, nausea, and abdominal pain and has a long list of contraindicated interacting medications, including several used to treat HIV and certain infections, related to its narrow therapeutic index.⁴

Neither drug carries an FDA-approved indication for long COVID, and pharmacists fielding questions from patients or prescribers should be prepared to discuss that this trial's findings do not establish a new approved use for either agent.

What This Means for Long COVID Care

The Centers for Disease Control and Prevention (CDC) defines long COVID as a chronic condition present for at least 3 months following SARS-CoV-2 infection, with symptoms that can improve, worsen, or persist over time. There is currently no approved laboratory test to diagnose it and no approved treatment.⁵

The CDC clinical guidance for health care providers describes long COVID as an infection-associated chronic condition that can affect one or more organ systems, and it recommends an individualized, symptom-focused approach to management, including FDA-approved and OTC medications tailored to a patient's most burdensome symptoms, alongside rehabilitation planning and validation of patient-reported symptoms. The CDC guidance also notes that some patients with long COVID benefit from symptom-management strategies borrowed from myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, and other post-infectious conditions, including strategies to manage post-exertional malaise.⁶

This trial adds evidence that specialist, multidisciplinary long COVID care, rather than any single repurposed drug, is what most reliably improves fatigue in the near term. For community and health-system pharmacists, colchicine and antihistamines may offer patients a modest, time-limited symptom benefit as part of a broader care plan, but rivaroxaban and other anticoagulants are not supported for this use, and none of the 3 drugs studied should be presented to patients as a durable fix for long COVID fatigue.

REFERENCES

1. STIMULATE-ICP consortium. Efficacy and safety of rivaroxaban, colchicine, and famotidine–loratadine with specialist supportive clinical care for fatigue in patients with post-COVID-19 condition in the UK: a multisite, open-label, randomised controlled trial. Lancet Infect Dis. 2026. doi:10.1016/S1473-3099(26)00242-2.

2. Commonly used drugs show small benefit for long Covid fatigue. News release. University College of London. July 8, 2026. Accessed July 15, 2026. https://www.eurekalert.org/news-releases/1135110

3. Merative, Micromedex. Rivaroxaban (oral route) - description and side effects. Mayo Clinic. Updated June 1, 2026. Accessed July 15, 2026. https://www.mayoclinic.org/drugs-supplements/rivaroxaban-oral-route/description/drg-20075013

4. Merative, Micromedex. Colchicine (oral route) - description and side effects. Mayo Clinic. Updated June 1, 2026. Accessed July 15, 2026. https://www.mayoclinic.org/drugs-supplements/colchicine-oral-route/description/drg-20067653

5. Centers for Disease Control and Prevention. Long COVID Basics. CDC. Updated May 6, 2026. Accessed July 15, 2026. https://www.cdc.gov/long-covid/about/index.html

6. Centers for Disease Control and Prevention. Long COVID Clinical Guidance. CDC. Updated March 9, 2026. Accessed July 15, 2026. https://www.cdc.gov/long-covid/hcp/clinical-guidance/index.html