Clinical trial in the care of COVID

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As the COVID-19 pandemic continues and the evidence evolves, clinical judgment is the end result for clinical care, according to Adarsh ​​Bhimraj, MD, of Cleveland Clinic, and James Walter, MD, of Northwestern. Medicine, Chicago.

In a debate / debate presented at SHM Converge, the annual conference of the Society of Hospital Medicine, Bhimraj and Walter took part in a friendly debate on the value of remdesivir and tocilizumab for hospitalized COVID-19 patients.

Bhimraj defended the use of remdesivir or tocilizumab in hospitalized patients with COVID-19 pneumonia and Walter filed the case against its use.

Referendum on Remdesivir

The main sources referred to by the presenters with regard to remdesivir were the WHO Solidarity Process (N Engl J Med. 2021, 11 February. doi: 10.1056 / NEJMoa2023184) and the final report of the Covid-19 adaptive treatment trial (ACCT) (N Engl J Med. 2020, 5 November. doi: 10.1056 / NEJMoa2007764).

“The‘ debate ’is partly artificial,” and it aims to illustrate how doctors can use their own faculties and clinical reasoning to make an informed decision when treating patients with COVID-19, Bhimraj said.

The ACCT trial compared remdesivir with placebo in patients with COVID-19 severe enough to require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation. The main result of the study was the timing of the recovery, and “the devil is in the details,” Bhimraj said. The results that doctors should look for in studies are those that are important to patients, such as death, disability and discomfort, he noted. Disease-oriented endpoints are easier to measure, but not always significant for patients, he said. The study showed an average 5-day decrease in the disease, “but the fact is that it showed no mortality benefit,” he noted.

Another comprehensive, open-label study of remdesivir in 30 countries showed no drug-associated survival benefit compared to the standard of care, Bhimraj said. Patients treated with remdesivir remained in the hospital longer, but Bhimraj said he believed it was a bias. “I think the doctors kept the patients in the hospital longer to give the treatment instead of the treatments themselves prolonging the duration of the treatment,” he said.

In conclusion to remdesivir, “solid data show that there is an early recovery,” he said. “At least for serious illnesses, even if there is no mortality benefit, there is a role. I argue that if someone asks if you want to use remdesivir in patients with severe COVID-19, say yes, especially if you value the people leave the hospital earlier. In a crisis situation, there is a role to play. “

Walter discussed the “opposite” side of using remdesivir. “We can start with a pre-data hypothesis, but integrate new efficacy data into a post-data hypothesis,” he said.

Walter made several points against the use of remdesivir in hospitalized COVID-19 patients. First, it has not shown any improvement in mortality and may increase the length of hospital stay, he noted.

Data from the ACCT-1 trial and the WHO solidarity trial showed “no sign of a mortality benefit,” he said. In addition, the World Health Organization, the American College of Physicians and the National Institutes of Health recommend remdesivir for patients who require mechanical ventilation or oxygenation of the extracorporeal membrane, he said. Efficacy when used with steroids is still unclear and long-term safety data is missing, he added.

Take Tocilizumab

Tocilizumab, an anti-inflammatory agent, has been shown to have an impact on several surrogate markers, in particular C-reactive protein, temperature, and oxygenation. Bhimraj said. He reviewed data from eight published studies on the use of tocilizumab in patients with COVID-19.

It could be said that some trials may not have been fed properly and, in combination, some trials show an effect on clinical deterioration, if not a mortality benefit, he said.

Consequently, in the context of COVID-19, tocilizumab “should be used at the beginning of the disease process, especially if the steroids do not work,” Bhimraj said. Despite limited evidence, “there is a niche population where this can be beneficial,” he said.

In contrast, Walter took the position of skepticism about the value of tocilizumab for patients with COVID-19.

It should be noted that decades of research show that tocilizumab has shown no benefit in patients with sepsis or Septic shock, or those with acute respiratory distress syndrome, which have similarities with COVID-19 (JAMA. September 3, 2020. doi: 10.1001 / jama.2020.17052).

He cited a research letter published in JAMA in September 2020, which showed that cytokine levels were in fact lower in critically ill patients with COVID-19, compared to those who had conditions such as sepsis with and without ARDS.

Walter also cited data on the questionable benefit of tocilizumab when used with steroids and the negligible impact on mortality in hospitalized COVID-19 patients seen in the RECOVERY trial.

Limited data mean that COVID-19-related therapeutic decisions are more nuanced, but can be made, the presenters agreed.

Ultimately, when it comes to deciding whether a drug is effective, useless, or harmful, “what we need to do is consider the vast majority of evidence,” Bhimraj emphasized.

Bhimraj and Walter had no relevant financial conflict to reveal.

This article originally appeared on MDedge.com, which is part of the Medscape professional network.





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