QCOSTARICA – The first 16 patients who received equine serum as an experimental treatment for the effects of COVID-19 have already returned home and are under surveillance, as part of the clinical trial protocol. Six others died.
“Many were very complicated, with an average age of 70 years, and other pathologies, such as poorly controlled hypertension or others, and that, as a result of the disease and its progression, had greater complications that led to death,” said Willem Buján, one of the researchers in charge of the project.
Buján added with concern that one of the problems they faced is that (the patients) “are arriving very late (to get medical attention), and that makes them very complicated.”
Alfredo Sanabria, coordinator of the investigation, indicates that, of those six people who died, four were admitted with severe pathology and in a very short time they evolved to critical. The other two had various risk factors for complications.
For scientists, the trial has been successful, so far, and they are ready to design protocols with a view to the next phase where the best doses are determined and tested in more people.
This investigation began on September 7 in two men and two women, aged 43, 60, 66 and 77 years old. Subsequently, it was extended to another 23 people in the hospitals Mexico (5 patients), Calderón Guardia (6 patients), San Juan de Dios (10 patients) and the Specialized Attention Center for Covid-19 Patients (CEACO) (6 patients).
The researchers tested two different versions of the serum developed by the ICP-UCR specialists with plasma from horses. In this phase, 27 people participated in the experimental treatment: 13 received one type of serum and the remaining 14, the other type.
“The laboratory results did not indicate differences in efficacy between one formulation of the serum and another, that is why both are tested in people,” said Alfredo Alape, researcher at the Clodomiro Picado Institute of the University of Costa Rica (ICP-UCR), the institution that designed the serum.
The serum is applied intravenously to patients. They are non-critical patients. It is intended that patients do not need more than ten days of hospitalization in order to stop the virus and neutralize its action. People with longer hospitalizations or in critical condition may not see much improvement from the serum.
The intention of the research is not only to determine how safe and effective the serum is, but also which of the two versions gives better results.
This is a double blind trial. This means that neither the participant nor the doctor knows the type of serum they receive.
Who received the experimental serum?
Authorities of the Caja Costarricense de Seguro Social(CCSS) – Costa Rican Social Security Fund Costa Rican Social Security Fund – and the ICP-UCR indicated that 17 men and 10 women between 31 and 77 years old were recruited, with an average age of 59.6 years.
Of the participants, 17 had a moderate evolution of COVID-19 and 10 a severe case. They were given a 10 milliliter dose of one of the two sera, applied between September 6 and 18. Each participant is followed up for 24 days to analyze their evolution.
Of the 16 patients who have already returned home, it is known that eight received one type of serum and the other eight, the other. They were hospitalized on average 10.1 days and have an average age of 55.5 years.
75% of those already at home had a moderate case of the virus and spent on average three days less in the hospital than those who were more serious.
The researchers note that, overall, there is more hope in those who are younger or have a less severe case of the disease. However, these are still preliminary estimates, since the analysis and follow-up of the participants is still ongoing.
Results: safety and efficacy
According to Sanabria and Buján, very satisfactory results were seen in the safety of the product. Safety is determined when the side effects produced by the experimental therapy are less than the benefit.
It was determined that 88% of the adverse effects were related to the evolution of the disease and not to the serum.
Within what was observed, the participants reported feeling drowsy (very possibly caused by being administered an antiallergic before placing the serum), allergy and rash, pharyngeal discomfort and weakness.
“We see a very, very good security profile, ”said Sanabria.
It is still early to know the efficacy results since the production of antibodies and the action of the immune system must be analyzed, but doctors already see some.
“The most notable thing is that patients who are on supplemental oxygen, that during the course of the days that oxygen therapy decreases. Also in some discharges, there was a patient who returned home on the third day, something very, very fast in patients with COVID-19,” said Buján.
Sanabria added the story of a patient who came in severe and began to behave as moderate after receiving the serum, to which on the second day he was already sitting in bed (in the hospital) drinking coffee.
For scientists, this is a very big step, since it is the first treatment to be tested in our country and it is made in Costa Rica from scratch.
Research without phase I
This study began in phase II of research, where it was sought to verify the effectiveness of both versions of the serum and compare them to see which is more effective. This means that phase I was “skipped” and straight phase II.
What does this mean? Once a possible medical treatment proves effective in a laboratory, three phases of clinical trials are conducted in humans to approve its use.
After the product is approved, a fourth phase is carried out to see how its long-term efficacy behaves or if possible rare adverse effects appear.
For Román Macaya, executive president of the CCSS, the long experience of Clodomiro Picado with antivenom and the large number of people who have used them during decades, in this case it was not considered necessary for the Phase I.
“The phase I study is not carried out because these are done with healthy volunteers. And, in healthy volunteers, we already know what the consequences are of administering antibodies in a human body; it is done every day with antivenom. They are products (equine plasma) made with the same protocol, but aimed at a different target, which is the virus (that produces COVID-19),” Macaya explained at the time.
It is still early to know when a final product will be available, as there is much more to investigate.
For scientists, the next step is to design a phase II B study, in which, after submitting the protocol to scientific ethics committees for their endorsement.
According to Sanabria and Buján, it is expected to have about 50 people at the beginning and later, if possible, increase to another 50.
The possibility would be to try different doses to see which is more effective. It must also be defined if there will be a group of patients with placebo, something that would be determined by scientific ethical committees.
“The basis of this is plasma therapy, and international studies say that it is more effective when it is administered sooner, so we also look to start applying equine serum earlier in the evolution of the disease,” said Buján.
There is no date yet to begin this phase of the study, as phase II A studies must first be completed.