With the Delta variant causing the number of COVID-19 cases and deaths to climb, developing new treatments quickly and safely is critical. Led by the clinical research team at the Lankenau Institute for Medical Research (LIMR), part of Main Line Health, the health system's four acute-care hospitals are part of a cutting-edge trial designed to do just that.
Main Line Health is among 20-plus health systems—and one of the few community health systems nationwide—participating in the I-SPY COVID-19 trial, giving its critically ill COVID patients access to state-of-the-art therapies. Only patients receiving a high volume of oxygen or on a ventilator are eligible. Studies estimate that patients placed on a ventilator have only about a 50% survival rate.
The trial's unique setup involves testing four drugs concurrently in addition to administering the existing backbone of approved therapies to all eligible patients. This standard-of-care regimen includes remdesivir, an antiviral drug; dexamethasone, a steroid medication; and tocilizumab or baricitinib, which are immunomodulating drugs. Study participants have an 80% probability of receiving one of the four trial drugs added to their regimen. The other 20% are part of the control group and receive no trial drugs.
Therapies found effective after a certain number of patients are enrolled will "graduate," at which point they will be part of a larger study or, if patient improvement is robust, could move into the standard of care when appropriate. Ineffective drugs are dropped. Each time testing of a drug is completed, another is rotated into the trial.
"I'm so proud that, as a community hospital, we can be part of a collaborative with larger university centers and help in the discovery of new agents that can help our sickest patients," said Eliot Friedman, MD, the lead investigator of the I-SPY trial for Main Line Health on behalf of LIMR. "It's an important endeavor, particularly in such a tragic situation where the pandemic has caused so much loss of life."
"Throughout its nearly 100-year history, LIMR has been dedicated to moving treatments from the study bench to the patient's bedside as quickly and safely as possible," said George Prendergast, LIMR's president and CEO. "I can think of no better example of serving that mission than the I-SPY trial. We're helping make a real difference against the greatest health threat of our time."
The I-SPY platform for simultaneously testing multiple agents already had a 10-year track record of safety and effectiveness in the treatment of breast cancer when the Quantum Leap Healthcare Collaborative, a nonprofit organization focused on uniting patient care and research, provided it for COVID-19 research in April 2020.
Because it is an early phase trial, I-SPY COVID-19 involves a smaller number of patients per experimental treatment arm than later-stage trials, allowing researchers to test drugs more quickly. Once 125 patients are enrolled nationally, the treatment arm is closed, and another drug tested.
"Safety is paramount in the trial," said Paul Gilman, MD, director of LIMR's clinical research center. "Unlike standard clinical trials, efficacy and safety data that are collected and analyzed during the course of it can lead to modifications of the trial while it is being conducted. Measures of safety are tracked and reported by the research team at Main Line Health and monitored by a national safety committee. Ongoing evaluation of safety is critical to the conduct of the trial and our ability to offer these state-of-the-art therapies."
Some of the drugs being evaluated have been around for many years and are approved for other uses. Others are new.
Patients and caregivers generally have one of two reactions when offered the chance to participate, said Christina Angelucci, who is senior clinical research coordinator for LIMR and oversees day-to-day operation of the trial. Some are resistant, although often they still can be convinced to participate.
"We need to remind them that we are just adding to the standard of care they are already receiving," Angelucci said. "Plus, they get another layer of oversight, because they have our team along with the physician team already treating them."
Others want to start as soon as possible. In fact, after receiving the prescribed four days of a monoclonal antibody treatment, one man was doing so well he asked if he could stay on it an extra day."I had to tell him, 'Sir, that's not how it works!'" she said, laughing. "But it was great. He was really seeing such a positive result from the infusion. It kind of put a smile on everyone's face who interacted with him and assisted with his care here."