Penn Is Enrolling Pregnant Women in a COVID-19 Clinical Trial. Here’s Why That’s Important
Of the 900 COVID-19 clinical trials launched around the world, very few have been related to pregnancy — even though pregnant women are more likely to have worse outcomes from the virus than non-pregnant women. Penn’s convalescent plasma trial is working to change that.
Remember convalescent plasma?
Early in the pandemic, researchers had the idea of gathering blood plasma from patients who’d recovered from COVID-19. They presumed those patients would have developed antibodies in their blood plasma that could be infused in other patients who needed an antibody boost to fight the virus. The idea isn’t entirely new. Convalescent plasma has been used in the past to treat patients during measles and influenza outbreaks.
So, it was no surprise that, in August, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for convalescent plasma to be used in hospitalized patients with COVID-19. Some COVID-19 patients who received convalescent plasma believed it made all the difference in their recovery from the virus. But for researchers to prove the treatment was effective in improving outcomes for all COVID-19 patients, they’d have to conduct some clinical trials.
In April, Penn Medicine launched its Convalescent Plasma therapy study for COVID-19 with a two-fold goal: prove the effectiveness of blood plasma as a treatment for COVID-19 and enroll a population that has been largely ignored during recruitment for other COVID-19 studies — pregnant women.
According to the Journal of American Perinatology, of the 900 COVID-19 clinical trials launched around the world as of June, less than two percent were related to pregnancy, and most of the trials either explicitly exclude or do not address pregnancy at all. It’s an issue that Penn’s assistant professor of medicine, Katie Bar, says has been limiting clinical studies for years.
“There is a lot of history of clinical trials not enrolling a full representation of our society; that has been going on forever and a day,” said Bar, the lead investigator on Penn’s convalescent plasma trial. “We have issues with representation in clinical trials for a whole bunch of different groups, including women, and it’s mostly because clinical trialists want to get their trials done as quickly as possible. So, the people who are the most enfranchised to healthcare and the most trustful of the system are the easiest to enroll. It takes more effort to reach different groups.”
Bar’s team decided to take the extra effort to enroll pregnant women in its non-pregnancy specific clinical trial — a first for the institution. It’s a boon for pregnant women as two new studies from the Centers for Disease Control suggest pregnant women with COVID-19 could be at a higher risk for complications of the virus than non-pregnant individuals who get the infection. In one study of 400,000 women with COVID-19, those who were pregnant were likelier to be admitted to the intensive care unit (ICU), to be intubated for ventilation, and to die than women who weren’t pregnant.
“We know that being pregnant places a lot of stress on a woman’s body and we know that any form of immune compromise potentially hampers your ability to fight off infections. Given the physical and immunological changes of pregnancy, it makes sense that pregnant woman would be at greater risk,” Bar said. “So, I think those studies are super important because we definitely want to have as good a sense as possible about what the risks are for them and how we can intervene to hopefully allow them to have the best outcomes possible.”
Penn’s Phase I convalescent plasma trial aims to assess the safety and efficacy of the treatment when used in severely ill, mechanically ventilated participants with pneumonia due to COVID-19. Bar says the trial has been open to pregnant women from day one, and over five months, no pregnant women were enrolled. Then suddenly, this month, they enrolled two. As Bar sees it, that’s both good and somber news.
“Unfortunately, the community spread of this virus has really increased. So, we went from having no pregnant women with any sort of hypoxia or severe enough pneumonia that they would qualify for an interventional trial to, in the past couple of weeks having multiples,” Bar said. “So that’s a sad thing but it’s also nice for us to have the ability to offer this trial to pregnant women.”
The study will enroll 50 eligible adults, 18 years old and older, who will receive two units of convalescent plasma collected from compatible donors who have recovered from COVID-19 in addition to standard care. Bar’s team will then follow up with participants at 15, 22, 29 and 60 days to see if the treatment improves their condition with no serious adverse events.
Bar’s team is steadily moving toward its primary trial completion date of December 31st. But much has changed in the realm of COVID-19 treatments since Penn launched this study in the spring. The controversial treatment remdesivir managed to coast to FDA approval and the monoclonal antibody drug, Bamlanivimab, earned an emergency-use authorization from the FDA. Meanwhile, convalescent plasma has largely been shifted to the background as a viable treatment option for the virus. Mixed results from early clinical trials seemed to shift the public and some researchers’ faith in it as a solution.
Bar believes that, even if the treatment ends up taking a backseat to a more sophisticated treatment in America, it could be a viable option for other countries. Most important, she says, we need to know if it works.
“In terms of my optimism, I don’t know how optimistic I am. I think that it’s important to know if convalescent plasma, in the right clinical scenario can be helpful because I do think that even as the U.S. moves on using convalescent plasma because we have a really great antibody monoclonal antibodies based drug, that drug is going to be very expensive and that may not be the sort of thing that all the health systems around the world are going to be able to afford,” she explained. “So, it’d be nice if we knew when convalescent plasma works, and if it does help, this could be a rapidly scalable intervention that people around the world could use.”
The Director of Penn’s Prematurity Prevention Program, Michal Elovitz, played a critical role in enrolling pregnant women in the trial. She remains hopeful that the study will prove convalescent plasma works for patients with COVID-19, including moms.
“What would be so great, in the simplest of terms, is if we find convalescent plasma works for a subset of patients with COVID, and when that paper comes out, instead of saying, Huh, I wonder if it works for pregnant women too?, I will be able to say whether it does or not, because they were included.”