Stanford Medicine trial: 15-day paxlovir therapy safe, but no clear benefit against long COVID | News Center

Midway through the study, the data were submitted to an independent group for preliminary analysis, and the researchers determined that safety was good but that benefits were not yet clear, so they continued the trial but stopped recruiting new participants.

At 10 weeks, the pre-specified time point for the final comparison, there were no statistically significant differences between the two groups in terms of the study's primary endpoint — reduction in the severity of the six core symptoms. There were also no detectable differences between the two groups in terms of a number of secondary outcomes, including sitting and standing blood pressure and heart rate, and performance on a one-minute “sit-to-stand” test (in which subjects are asked to sit in a chair, stand up, and sit back down as quickly as possible for one minute).

However, the 15-day treatment was safe: One serious adverse event possibly related to the study (hepatitis) occurred in the placebo group, but three serious adverse events in the Paxlobid group (blood loss anemia, forearm fracture, and melanoma) were determined to be unrelated to treatment.

“One reasonable conclusion from our findings is that paxlobidi could be safely administered for longer periods, for example in newly infected patients who are immunocompromised,” Singh said.

The challenge of being the first

Singh said the lack of clinical response in the recent trial does not rule out the possibility that Paxlobidi may prove to reduce long-COVID symptoms in some people, but he noted there are too many unanswered questions: “Should we have tested patients who developed symptoms after 7-8 months instead of 16-17 months? Should we have treated them for longer? Were we testing the right patients in the first place? Maybe only a subset of symptoms respond to antiviral treatment.”

If Long COVID is not a single entity, different people exhibiting different clusters of symptoms may require different treatments.

Singh said even routinely testing subjects for the presence of latent SARS-CoV-2 early or after treatment, which by definition is hidden beyond the reach of the immune system and perhaps a simple blood test, is not possible because no easy, non-invasive and cheap test exists.

Interestingly, on average, the overall symptoms of participants in both the intervention and placebo groups improved over the course of the study. This could be good news – it suggests that Long COVID symptoms generally subside over time. On the other hand, it could also be a placebo effect: the extra care and attention from nurses, doctors, and other healthcare professionals, and the expectation of relief from the medication, could lead placebo recipients to feel subjective improvement and even experience objective improvement.

Furthermore, in the absence of validated objective biomarkers, it was difficult to determine whether the improvements reported by one person were greater than those of another.

Results from numerous chemical, immunological and wearable tests administered throughout the trial could help the Stanford Medicine team determine whether some people benefited significantly more from paxlobidi than others and, if so, how to distinguish between them prior to treatment or entry into new trials.

“We hope to report the results of our analysis of these measurements within four to six months,” Singh said. The results could inform other clinical trials currently underway or in the planning stages testing the ability of Paxlobid and other drugs to combat long-term symptoms of COVID-19. The trials are sponsored by the National Institutes of Health and Pfizer, the company that developed, manufactured and sells Paxlobid.

Researchers from Kaiser Permanente Northern California and Pfizer contributed to the study.

The trial was funded by Pfizer.