Due to negative results, the I-SPY COVID Trial is no longer evaluating cyproheptadine to treat critically ill COVID-19 patients.
Today, Quantum Leap Healthcare (QLHC) announced the termination of the cyproheptadine arm of their sponsored I-SPY COVID Trial. Cyproheptadine was being evaluated as a potential treatment for critically ill COVID-19 patients.
“While we were hopeful that cyproheptadine would specifically target biological pathways that are overactive in patients with severe COVID-19, it did not ultimately improve patient outcomes in this trial,” said Sara Auld, MD, MSc, a lead investigator of I-SPY COVID. “We will continue to evaluate whether there may have been subgroups of patients who did have benefit and remain committed to identifying effective treatments for people with COVID-19."
Cyproheptadine is a first-generation antihistamine commonly used to treat allergies, headaches, and motion sickness. It was hypothesized that cyproheptadine could also alleviate hypoxia and improve clinical outcomes in COVID-19 patients.
COVID-19 patients in critical condition may experience pulmonary edema and acute respiratory failure. Platelet activation is indicated in COVID-19 pathology, but serotonin, a mediator of platelet activation, could boost immune modulation.
As an antiserotonergic agent with a substantial safety profile, cyproheptadine was studied to see if it could reduce platelet and endothelial dysfunction in the lungs of COVID-19 patients.
The I-SPY COVID Trail tested cyproheptadine in hospitalized and critically ill COVID-19 patients, with 2 primary endpoints: reducing recovery time and risk of mortality.
During the trial, 8 mg of cyproheptadine was administered to 35 test participants every 8 hours for 10 days. If a patient weighed less than 48 kg, dosage was reduced to 6 mg every 8 hours for 10 days. All patients, the 35 cyproheptadine subjects and 61 control subjects, received dexamethasone and remdesivir as standard-of-care.
The probability that cyproheptadine could increase COVID-19 recovery rate was estimated to be 0.1%, and the probability that it could reduce mortality was estimated to be 14.4%.
Additionally, a significantly higher proportion of the trial’s cyproheptadine recipients had serious adverse events, adverse events of special interest, and adverse events. All these factors led to the discontinuation of cyproheptadine as a potential agent to treat critical COVID-19.
“One of our future goals is to improve biomarker classification of COVID-19 severe illness,” emphasized Fady Youssef, MD, another lead investigator of the study. The I-SPY COVID Trial will continue, with the team urgently looking for additional agents to test for efficacy against COVID-19. Youssef called this work, “A critical part of the I-SPY COVID trial which will hopefully help us to find effective agents for this incredibly challenging and devastating disease.”