The ELISPOT-TC multicenter clinical trial aims to evaluate the efficacy of a preventive strategy to deal with cytomegalovirus infection in heart transplant patients. This strategy is based on the response of the T lymphocytes of each person against the cytomegalovirus. The Cardiology Department of Hospital de Bellvitge and the BIOHEART research group of IDIBELL are leading the trial, which will have its first results in mid-2024.
This trial has been financed by the Carlos III Health Institute through R&D projects call in 2019, and by a grant from the Spanish Society of Cardiology.
After closing a complex patient recruitment period, especially due to the pandemic, the ELISPOT-TC trial is underway with the participation of 188 patients from a total of eleven Spanish hospitals that perform heart transplantation. When performing a transplant, the patient remains immunosuppressed, which increases the risk of contracting infections, especially at the beginning, or of reactivating previous infections that have already been overcome. Cytomegalovirus (CMV) is one of the most common microorganisms and at the same time one of the most dangerous in heart transplantation, because it is associated with other infections that can be very harmful, and with graft vasculopathy (the arteries of the new heart deteriorate).
Up to now, the approach to CMV infection has been carried out with two strategies: universal prophylaxis, that is, the administration of a drug in a preventive manner; or closely following up on the patient to facilitate treatment only when the appearance or reactivation of the virus is detected.
In this context, the trial applies a laboratory technique that studies the T lymphocytes of each patient, which are cells that play a key role in the control of viral replication and in the survival of CMV. “If the lymphocytes react in contact with the virus, it means that the patient’s body is capable of responding to CMV on its own, while if they are not activated it will not,” explains the HUB cardiologist and IDIBELL researcher, Elena Garcia-Romero.
“The final goal of the trial is to verify if this procedure is not inferior in results to universal prophylaxis, so that the possible side effects of the preventive administration of the drugs can be avoided, such as interaction with immunosuppressants”, indicates Dr. García-Romero. The results of this assay will allow personalization of treatment and not administering the drug when it is not necessary, since T lymphocytes already act against cytomegalovirus infection.
Infections in heart transplant patients are frequent, especially during the first year after the intervention. In universal prophylaxis, the drug to prevent infection is taken immediately after the transplant, so that it coincides with the administration of immunosuppressants to prevent rejection. “The combination of both elements can cause the patient’s defenses to be greatly reduced,” explains Dr. García-Romero. In this line, one of the most important side effects of the drug is leukopenia, a decrease in leukocytes that increases the risk of infections and can lead to a readjustment of immunosuppressants. In addition, once universal prophylaxis is stopped (after between 3 and 6 months) there is a risk of late infection, of reappearance of the virus, even if it has been overcome.
The ELISPOT-TC clinical trial takes as its starting point the work of Dr. Oriol Bestard’s group at the Vall d’Hebron Hospital, which has studied cellular immunity against cytomegalovirus in kidney transplants. The Microbiology and Infectious Diseases services of Hospital de Bellvitge are collaborating on the trial.