Q&A: How to request remdesivir for patients with COVID-19
[Editor’s note: Gilead Sciences announced that it is no longer accepting new individual compassionate use requests for remdesivir due to overwhelming demand, except in cases of severe disease in children and pregnant women. It is transitioning to making the drug available under expanded access programs. For more on that, please see this story.]
Physicians around the world are repurposing old drugs as potential therapies for critically ill patients with COVID-19, including the HIV combination therapy lopinavir-ritonavir and the antimalarial chloroquine. WHO announced this week that it will test some of these treatments in an international trial, and other studies are underway or have been announced. Results of a study published this week showed no benefit from lopinavir-ritonavir in hospitalized adults with severe COVID-19.
Remdesivir (Gilead Science), an investigational antiviral developed as a potential therapy for Ebola, will be included in the WHO study and is already being tested against COVID-19 in five clinical trials. The first began last month at the University of Nebraska.
Infectious Disease News Editorial Board Member Peter Chin-Hong, MD, professor of medicine and director of the transplant infectious disease program at the University of California, San Francisco (UCSF), has managed patients with COVID-19, including some who are critically ill, and has requested remdesivir for compassionate use. He said UCSF is now part of one of the trials.
We spoke with Chin-Hong about his experience managing patients with COVID-19 and requesting remdesivir, and the fears facing members of the medical community who are on the front lines of this pandemic. – by Gerard Gallagher
Q: Do you have advice for physicians who would like to request remdesivir?
A: You need to work with a pharmacist. Pharmacists are your friends. And you need to do some prework before you even see your first sick patient so when the time comes, you don’t have to scramble to get everything done. Prework might include calling the institutional review board locally to tell them what the situation is so they are prepared, having pharmacists build order sets in electronic medical records, getting the investigational pharmacists up to speed, and identifying who will give consent to use the drug if a critically ill patient is unable to do so. The adage is, “Any consent is better than nothing.” But if you can’t find anyone, you can write that on the chart and will still be able to give them the drug.
The first step to communicate with Gilead is to submit information electronically. Everything is online. [Editor’s note: For the link where you can submit a request, please see the infographic included with this story.] In a regular situation, you pick up the phone and talk to someone. But you can’t talk to anyone right now. There are just too many people calling. The pharmacist helped me with that first step, submitting the form. I gave her some clinical data, and she was able to do most of it. The critical criteria for the drug exemplify somebody who is critically ill.
The main problem is the exclusion criteria, which are very strict. Many patients who are critically ill or septic wouldn’t qualify. I’ve heard rumors that the CDC is working with Gilead to see if it can relax the criteria. An interesting and controversial criterion that’s not understood by the population is concomitant use of antiviral drugs. We used Kaletra (lopinavir-ritonavir, AbbVie) and were worried that it would exclude patients from the trial of remdesivir for compassionate use. But it was OK. They just don’t like the patient to be on it at the same time. A lot of people might be turned off from applying for remdesivir, thinking that their patient may not be eligible. But the reality is that they allow patients to have used an antiviral before, as long as it’s not used at the same time as remdesivir. So don’t be discouraged by that language, which you will see on the website.
That’s the start. You have to jump through a lot of hoops in the next 72 hours after the initial request. It’s almost like a Broadway show, where you are coordinating some complex choreography. You’re the middle man between the FDA, Gilead and the institution. [Editor’s note: Steps are shown in the infographic.] In my experience, Gilead has been very responsive given the circumstances they’re facing, and very professional. Once they approve it, a lot of the other stuff comes easily but it just takes time because they are backlogged.
Q: To provide remdesivir for compassionate use, Gilead requires that a patient have confirmed COVID-19 infection “with significant clinical manifestations.” What are some clinical features that might lead a physician to request remdesivir?
A: A typical patient will be in the ICU, on a ventilator and have PCR confirmation of SARS-CoV-2 infection. They may have acute respiratory distress syndrome, sepsis, altered mental status or multiorgan failure. So, someone in the ICU with one of those things. If someone is on extracorporeal membrane oxygenation, they may not qualify for compassionate use or a trial. It’s kind of like Goldilocks: You have to be sick enough but not too sick, which is hard with a 72-hour timeline for this process because a patient’s condition can change in 72 hours.
Q: How is it being used to treat patients?
A: It’s a 200 mg loading dose, then 100 mg daily for 2 to 10 days. You can use it for up to 10 days. They give you a range so you can decide when you want to stop it if the patient is getting better. In my experience, we’re probably just going to continue to use it the whole time.
Q: Do you have hopes that the drug will be effective?
A: Of all the drugs, it’s one that people have hope for. It makes sense biologically. It interacts with the viral polymerase. There are promising case reports and animal data. It’s not a toxic drug. It’s generally well tolerated, which is amazing. When you think of a drug like that: If it’s not going to cause a patient that much harm and you have a little evidence of benefit and the patient might die without treatment, of course you want to use it as much as you can. Scientifically, we always want evidence. But the risks are very low as we know them.
Q: As a practicing physician, do you worry about your own health during this pandemic?
A: All the time. I saw a really sick patient. And, of course, we know this stuff inside out. I’ve done it a thousand times: mask, gloves. And with Clostridioides difficile, we use a gown all the time. But this infection has so much meaning, and so much is unknown. It was scary. I was surprised. Before I went in, I went through all the steps with a nurse in the anteroom to make sure I was doing it right, because I just couldn’t think. People are more anxious about this disease. It’s so high stakes. The nurse was super reassuring, and when I came out, I had the nurse help me again.
Then I started having all these fears. What if I picked up coronavirus on my shoes by stepping around the bed and I bring it home and spread it all over the house? Someone might touch the floor and then get it. I know colleagues who have started keeping their shoes in the car and changing their shoes before going into their house. I know people who are staying in guest rooms because they are on the front line — ED physicians or nurses. When I come home, I shower before I even talk to family members. Those are things that people are doing to overcome their fears.
And then there is the personal fear of getting sick, although I’m not that fearful because in ID, we live with that fear all the time. I used to tell my medical students that I’m not afraid of anything, except maybe Ebola, because they were always asking me if I was afraid of getting something like Salmonella from eating some random food. But I think in ID you can be in two camps: You can be afraid of everything because you know too much, or you can be afraid of nothing because, what’s the point? There’s too much to worry about. I’m in the not afraid of anything camp, but it was very different with this infection. There’s a fear of making other people sick.
In ID, we’re very altruistic in general. It’s a special person who goes into ID, and I think we take a lot of pride in being at the forefront and that people are looking to us for guidance. I think this situation has restored a lot of mission and pride in what we do, kind of like the early HIV days. There’s a lot of purpose around who we are as a profession.
Disclosure: Chin-Hong reports no relevant financial disclosures.