The HonorHealth Research Institute and HonorHealth are enrolling patients with moderate to severe COVID-19 infections in a trial of atovaquone and azithromycin.
Conducted in collaboration with Translational Genomics Research Institute (TGen), the clinical trial is funded as an investigator-initiated clinical trial by HonorHealth Research Institute.
This is one of 10 clinical trials that the HonorHealth Research Institute is working on related to COVID-19 to understand the biology, spread and treatment of the disease. HonorHealth is enrolling about 25 patients in this study at HonorHealth Shea, HonorHealth Osborn and HonorHealth John C. Lincoln Medical Center. Eligibility criteria is at clinicaltrials.gov. For more information, email email@example.com.
“We historically have done lots of clinical trials in cancer,” said Dr. Michael Gordon, medical director, oncology clinical trials, clinical investigator.
“With the development of COVID-19 as a major scourge at this time, we pivoted our activities to develop a new research program on COVID-19. A portion of those trials are therapeutic, and a number are developing as an investigation to better understand the diagnostic criteria to establish COVID-19 recovery-based issues.”
With TGen, HonorHealth is working on a number of translational aspects to understand the biologic response to COVID-19.
“We know 80 percent of patients who are infected with COVID-19 tend to get a classic flu-like syndrome,” Gordon said. “It tends to last longer than we historically have seen with influenza. It can be present a week to two weeks with symptoms like fever, chills, sweats, muscle aches and pains, coughing and shortness of breath.
“It’s most of those symptoms that generate the concern leading to individuals getting tested for COVID-19.”
Nasopharyngeal swabs are the most common way that COVID-19 is diagnosed though they are not 100 percent accurate. Some patients may have negative tests even though they have the infection. The study will use interval nasopharyngeal swabs during treatment to quantify COVID-19 viral load as well as assess additional clinical and laboratory determinants to determine response to therapy.
“I think some of those asymptomatic individuals are people who had symptoms who historically didn’t think of being COVID-19 related. Now, we recognize it could be COVID-19 related. The persons who lose their sense of smell or taste, we’ve learned, probably have COVID-19.”
The test shows the burden of infectious individuals is actually larger than the number of people who medical professionals are testing and showing to be positive, he said.
Among the 20 percent of the patients who have more than just a routine symptoms, about 15 percent to 20 percent of the total population of individuals will have more severe side effects of the virus—shortness of breath, respiratory failure and the need to be hospitalized or be managed in ICU or on a ventilator than population of patients who run the highest risk for dying from COVID-19.
Gordon said patients who are sick and don’t need hospitalization could benefit from a treatment that may reduce the durations of illness and infectiousness. On the other side, the very sick patients who are in the intensive care unit might take part in the clinical trials and reduce the illness’ severity.
“We want to prevent them from dying and ensure, when they do recover, that we can maintain their quality of life,” Gordon said. “That’s the spectrum that we’re investigating as we begin this study.”
The combination of atovaquone and azithromycin has the advantage of less risk of cardiac side effects compared to the other potential COVID-19 treatments. Laboratory modeling suggests that atovaquone may be an active drug in the treatment of COVID-19 and its combination with azithromycin, studied in the rare infectious disease babesiosis, makes this an “intriguing combination to study in COVID-19,” he said.
Atovaquone given in liquid form and azithromycin commonly known as Z-Pak are administered to clinical trial patients over about 10 days. Pharmaceutical companies are looking at new drugs, but some are being repurposed, like these two, to treat COVID-19, Gordon said.
Remdesivir, a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences, has shown to shorten the amount of time patients have to be in the hospital, Gordon said. Gilead is one of many companies working to develop antivirals.
Another possible way of treating COVID-19 is through COVID-convalescent plasma, which Gordon calls “an interesting idea.”
“COVID-19 isn’t the first pandemic to have hit in the last decade to two decades,” he adds. “MERS and SARS taught us a patient who had been infected with a virus and recovers in part because their immune system generated antibodies against the virus.
“Those antibodies land on the virus like a smart bomb and cause the immune system to attack and kill the virus. Historically, we transfer that immunity from one patient to another by taking the antibody portion of that blood plasma and infusing it to the infected patient.”
HonorHealth is working with Vitalant, a nonprofit community blood service provider, to bring donors to undergo plasma pheresis. Then, the plasma is infused into acutely ill patients, a procedure that is considered investigational.
Gordon said it’s been widely discussed but the goal is to motivate the previous patients to visit a blood bank to donate plasma, as the antibodies cannot be generated in a lab.
“Those individuals can donate plasma every four weeks,” Gordon said. “The more people who donate plasma, the greater the number of available units. One of the big questions is where should we use that and who should receive it?
The clinical trial will look at the sickest of patients and seeing if the infusions coupled with medications help.
The atovaquone and azithromycin study is funded by and held by HonorHealth. Although, HonorHealth may invite other facilities around the state to take part.
“That’s a little bit of a challenge,” he said. “We’re in the process of creating an Arizona coalition against COVID. A COVID-19 Arizona coalition is what we would think of where everybody is coming together to work against a common foe.
“As we’re going through this process with the new clinical trial, we want to provide access as best as possible—not just to patients in HonorHealth, but to all patients.”
HonorHealth Research Institute’s Chief Operating Officer Dr. Kiran Avancha notes it’s exciting to have someone like Gordon, who’s an oncologist, pivot to conduct studies on COVID-19 because of the personalized medicine approach and immunological investigations, which are somewhat similar in both these disease states.
“We started right after we had the first wave of cases in Arizona, around March 2020,” Avancha said. “We were one of the first in the country to start looking into this atovaquone and azithromycin combination. This innovation came out of the HonorHealth Research Institute as a clinical trial for a direct impact on COVID-19 patients.”
Beth Gleason, HonorHealth Research Institute’s director of research administration, said the team has collaborated around the clock to build the program.
“We’re combining the strengths and expertise of our team members in designing protocols to provide additional treatment options for patients and providers, and to be supportive of the community with our research efforts here.”