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Beijing – In an open study at a clinic in Wuhan, treatment of seriously ill COVID-19 patients with the antiviral drug lopinavir / ritonavir has neither accelerated the elimination of the viruses nor reduced the morbidity and mortality of the patients. Some of the im New England Journal of Medicine (2020; doi: 10.1056 / NEJMoa2001282) published results, however, show that the use could not be entirely hopeless.
The active ingredient lopinavir has inhibited coronavirus C30 endopeptidase in laboratory experiments. In the 2002/3 SARS epidemic, lopinavir was used sporadically, as usual in combination with the P450 inhibitor ritonavir, which increases the plasma concentration of lopinavir. The experience was mostly positive.
In a clinical study, the outcome “death or lung failure” was only achieved by 2.4% of the patients compared to 28.8% in untreated patients, who, however, came from a historical comparison group, which limits the significance of the study (thorax 2004; 59: 252256).
It was obvious that lopinavir / ritonavir should also be used in patients with COVID-19. Under difficult conditions, doctors from the Jin Yin Tan Clinic in Wuhan managed to carry out a randomized (but not blinded) study in which a total of 199 patients aged median 58 years participated between January 18 and February 3.
The patients had been symptomatic and seriously ill for a median of 13 days, so they had to be treated in an intensive care unit. The lungs’ oxygen intake was restricted, and some of them had to be ventilated. In some patients, extracorporeal membrane oxygenation (ECMO) was required.
Under these difficult conditions, the additional administration of lopinavir / ritonavir has not achieved a safe clinical benefit. As Bin Cao from the Sino-Japanese Friendship Hospital in Beijing and staff report, it took a median of 16 days to recover in both groups if the patients survived.
In the meantime, treatment with lopinavir / ritonavir appeared to accelerate recovery, but the hazard ratio of 1.31 was not significant with a 95% confidence interval of 0.95 to 1.85. The 28-day mortality rate, the study’s primary secondary endpoint, was reduced to 19.2% compared to 25.0% in the control group. The difference of 5.8 percentage points was not significant with a 95% confidence interval of minus 17.3 to 5.7. The viral load in the smears did not differ between the two groups in the course of the study.
A modified analysis without 3 patients who died before starting treatment with lopinavir / ritonavir comes to a somewhat cheaper result. The treatment was now shortened by 1 day and the hazard ratio of 1.39 in the primary endpoint reached the significance level with a 95% confidence interval of 1.00 to 1.91. Such subsequent interventions in the study design are controversial.
However, lopinavir / ritonavir may remain effective in less severely ill patients. An overall limited antiviral effect of lopinavir / ritonavir against SARS-CoV in laboratory experiments could explain this, according to editorialist Lindsey Baden from the Dana-Farber Cancer Institute in Boston.
There would therefore be good reasons to investigate the effectiveness of lopinavir / ritonavir in COVID-19 in further studies, especially since the tolerability was good, even if 13 patients stopped treatment prematurely because of side effects. © rme / aerzteblatt.de