This phase 3, open-label RCT evaluated whether colchicine (500 µg twice daily), rivaroxaban (10 mg once daily), or famotidine–loratadine (40 mg/10 mg once daily) reduced fatigue versus usual care alone over 12 weeks in 778 non-hospitalised UK adults with long COVID, using the Fatigue Assessment Scale (FAS) as the primary endpoint.
All groups improved: mean FAS dropped ~4.3 points across the board (36.8 → 32.5). Colchicine (−1.49 pts, p=0.041) and famotidine–loratadine (−1.48 pts, p=0.038) showed small but statistically significant additional reductions vs. no drug; rivaroxaban did not (−1.06 pts, p=0.139). Crucially, these differences were gone at 24 weeks (12 weeks after stopping). Serious adverse events occurred in 8 of 778 participants (1.0%), with 5 events in 3 rivaroxaban-group patients.
- Open-label design may introduce bias in patient-reported fatigue scores. - Effect sizes (~1.5 FAS points) are well below the pre-specified clinically meaningful threshold of >4.6 points (>10% of 46-point scale). - Benefits did not persist after drug withdrawal, limiting long-term clinical relevance.
These three repurposed drugs are unlikely to provide meaningful or lasting fatigue relief for unselected long COVID patients — do not routinely prescribe them for this indication. Future research should focus on defined subgroups, combination regimens, or alternative delivery strategies.
