(090) Characteristics of Registered Clinical Trials Investigating Therapeutic Interventions for Long COVID

Background: Although many patients with COVID-19 recover within days or weeks, nearly 7% of individuals continue experiencing symptoms or adverse effects for months and years, a condition known as Long COVID. Given the high burden of Long COVID, several clinical trials are ongoing to find new drugs or repurpose existing drugs for Long COVID treatment.

Objectives: To characterize the study design and quality of currently registered clinical trials aimed to investigate therapeutic interventions to address Long COVID symptoms.

Methods: We used clinicaltrials.gov data and conducted a search to identify registered clinical trials exploring interventions to treat Long COVID registered through January 21, 2024. We included trials if they were investigating Long COVID, included a pharmaceutical or biologic therapeutic, used an interventional design, and listed treatment as their primary exposure. We used descriptive statistics to characterize Long COVID treatments, outcomes, and study design elements such as randomization, phase, blinding, sample size, and sponsor.

Results: Of 666 trials identified in the initial search on clinicaltrials.gov, 64 met the inclusion criteria. Across these 64 registered trials, 59 unique medications and biologics are being studied. Nearly two thirds (64.1%) of the trials focused on an individual symptom, with 26.6% exploring fatigue, 21.9% cognitive function, and 12.5% mental health as their primary outcomes. Nearly a sixth of trials (15.6%) investigated a combination of symptoms rather than one specific symptom in their primary outcomes. Of the 64 registered trials, the majority were in Phase 2 or earlier (73.4%), use randomization (82.8%) as the assignment mechanism, and follow a parallel intervention model (81.3%). For masking, the study design included blinding the participant in 70.3% of trials, the care providers in 54.7% of trials, the investigators in 71.9% of trials, and the outcomes assessors in 54.7% of trials. Overall, 45 trials (70.3%) included both randomization and at least double blinded masking. The mean enrollment size was 171 and nearly two-third of trials (64%) trials had sample size < 100.

Conclusions: Although registered trials for Long COVID treatment were well-designed, their small sample sizes limit their utility. Well-conducted target trial emulations can provide valuable real-world evidence to complement clinical trial results.