U.K. — Results from the STIMULATE-ICP trial, an open-label randomized study in the U.K., showed colchicine and famotidine-loratadine led to modest, temporary reductions in fatigue for long COVID patients, while rivaroxaban demonstrated no benefit. Amitava Banerjee, DPhil, reported the findings in Lancet Infectious Diseases.

The study enrolled 778 adults between August 2022 and August 2024. Patients were randomized to receive 12 weeks of twice-daily colchicine (500 µg), once-daily famotidine (40 mg) and loratadine (10 mg), once-daily rivaroxaban (10 mg), or no drug. All groups received usual care from a long COVID specialist and ongoing community support. The trial excluded patients with a previous COVID hospitalization.

The addition of colchicine resulted in a 1.49 point lower Fatigue Assessment Scale score compared to usual care over 12 weeks (P=0.041). The addition of famotidine-loratadine led to a 1.48 point lower score compared to usual care over the same period (P=0.038). Rivaroxaban added no benefit for fatigue reduction at 12 weeks. Across all trial groups, mean Fatigue Assessment Scale scores dropped from 36.8 at baseline to 32.5 at 12 weeks.

Fatigue Assessment Scale scores fell 4.4 points in the colchicine group, 4.8 points in the famotidine-loratadine group, and 4.4 points in the rivaroxaban group at 12 weeks. The no-drug group saw a 3.3-point drop. By week 24, 12 weeks after stopping the interventions, differences in fatigue scores between the drug groups and usual care were no longer present. Scores reached 32.7 in the colchicine group, 33.4 in the famotidine-loratadine group, and 33.4 in the rivaroxaban group. The no-drug group's scores declined from 34.2 to 34.1 by week 24.

Banerjee said, "Overall, our data do not support widespread clinical use of these drugs for fatigue reduction in long COVID." He added, "But our study does provide a framework to support second-generation, precision medicine, placebo-controlled trials of new and repurposed drugs and drug combinations for long COVID-associated fatigue." Banerjee also stated, "Our trial was done across 12 sites with broadly consistent care models, informed by NHS long COVID guidelines, in a broadly U.K.-representative population."

Tiffany Walker, MD at Emory University School of Medicine in Atlanta, noted that there are no validated disease-specific primary outcome measures for long COVID clinical trials and no FDA-approved treatments. Walker said, "It is possible that the drug effect seen here would be more robust if symptom severity variations were addressed."

Approximately one-quarter of study participants reported an adverse event. Rates were highest in the rivaroxaban group at 36%, followed by colchicine at 30%, and famotidine-loratadine at 26%. The usual care only group reported an 11% rate. Study limitations included an open-label design that may have been subject to placebo effects and expectation bias, and an inability to separate the effects of SARS-CoV-2 exposures, vaccination, or repeated infection on fatigue scores.