Photo: Professor Jens Lundgren
Danish patients and physicians have helped provide important answers in the search for the best to new treatment for patients with COVID-19: Patients in hospital do not have shorter admission times and better pathways if they are treated with the antibody LY-CoV555. This is clear from the first treatment results from ACTIV, the largest worldwide study on COVID-19, to which seven Danish hospitals have contributed. The results have been published in the prestigious New England Journal of Medicine.
Antibodies are proteins naturally produced by the immune system to combat infection, and they can potentially prevent a virus from infecting cells. The researchers in the international research network, INSIGHT, who are working together on the new study, will now continue to test another three different antibody treatments to clarify quickly whether these can help patients most seriously ill with COVID-19 in particular.
The clinical trials are being sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health in the US. Prof. Jens Lundgren from Rigshospitalet has been appointed to head the ACTIV trials. He explains that the research network behind the study can help to provide the world with some very quick replies as to whether a treatment has a positive effect on COVID-19, when it is best to administer the treatment over the course of an illness, and how it should be used.
“These results unfortunately lead us to conclude that the LY-CoV555 antibody treatment does not improve the outcome for patients in hospital with COVID-19. However, this does not mean that we have to drop all antibody treatments, because it may turn out that we find a different type of antibody treatment that does work,” said Jens Lundgren.
Ready for the next coronavirus
He explains that timing can also have great significance, because it means a lot when during an illness a treatment is given, and how it is combined with other treatments.
"It is crucial to find as many results as soon as possible, partly to continually optimise treatment under this pandemic. However, it is just as important to be better prepared in the event of another pandemic caused by a coronavirus,” said Jens Lundgren.
The CoV555 antibody treatment is manufactured by Ely Lilly and it has been approved in the US by the FDA under the name Bamlanivimab for treating people with mild and previous corona infections because it has proven to be able to reduce the virus infection in the early phase of the disease and to reduce the rate of hospital admissions. The researchers behind the new study have therefore examined whether it can also help people in hospital with COVID-19.
Call up of patients on the trial stopped before time
Already on 26 October 2020, when less than one-third of the 1,000 patients in the study had been included, the monitoring committee decided to stop calling in more patients, because it was evident that patients in treatment with the antibody were not having better results than patients in the placebo group. According to Jens Lundgren, one of the great strengths with the design of the study is that it is possible to move on quickly if an effect of the treatment cannot be demonstrated.
"We chose what is called adaptive design, which means that we can quickly and smoothly change the trials on the basis of the experience we and others gather. Moreover, several drugs can be tested at the same time and with a common placebo group, so that the fewest possible patients have to be included to test the highest number of treatments.
Treated in accordance with the best standards
The patients included in the study were all treated according to the best standards, and this means that they typically received the antiviral treatment Remdesivir, supplementary oxygen, and infection-inhibiting steroids when necessary. One-half of the patients received the antibody treatment as a supplement to the other treatment, while the other half received a placebo.
The researchers in the study examined the extent to which patients recovered within 90 days, and how early in the process they were discharged from hospital. On the fifth day of treatment, participants in the trial underwent an assessment of the degree of COVID-19 they had in order to determine whether the treatment was helping them, and whether it made any sense at all to continue treatment. Patients in the placebo group had equally good results in the assessment as the patients receiving treatment with the antibody. In other words, 50% of the patients undergoing treatment with the antibody were in the two best result categories, while the corresponding figure was 54% for the placebo group. The results showed that there was no difference between the two groups when comparing deaths and serious illness. It was therefore considered that it would be unethical to continue an ineffective treatment.
The patients in the study were admitted to 31 different hospitals throughout the world, of which seven were Danish hospitals. Researchers ran 314 patients through the study, of whom 161 received treatment with the antibody.
Read the scientific paper in The New England Journal of Medicine.