A phase II clinical trial has found that a combination of three drugs — interferon beta-1b, lopinavir-ritonavir, and ribavirin — plus standard care is successful in treating mild-to-moderate cases of COVID-19.
This three-drug combination also shortens the duration of viral shedding — that is, the period during which the virus is detectable in a person’s body and transmissible to others.
The results of the new multicenter, prospective, open-label, randomized trial now appear in the journal The Lancet.
The researchers recruited 127 participants between February 10 and March 20, 2020. These participants came from six hospitals in Hong Kong, China, where doctors had tested them for SARS-CoV-2 and obtained positive results.
On average, 5 days passed between the onset of symptoms and the start of treatment with the drug combination.
The team randomly assigned 86 of the participants to a group that received the combination and 41 of the participants to a control group.
In the combination group, participants took a combination of “lopinavir 400 [milligrams (mg)] and ritonavir 100 mg every 12 [hours], ribavirin 400 mg every 12 [hours], and three doses of 8 million international units of interferon beta-1b on alternate days.” The treatment lasted for 14 days.
In the control group, participants took lopinavir 400 mg and ritonavir 100 mg every 12 hours, also for 14 days.
The results revealed that the three-drug combination was safe and more efficient than lopinavir-ritonavir in relieving COVID-19 symptoms, reducing the period of viral shedding, and shortening the length of hospital stays.
Specifically, nasopharyngeal swabs showed that the average time before the virus cleared was 7 days in the combination group, compared with 12 days in the control group.
Side effects across both groups included nausea — which resolved with no intervention — and diarrhea, with no difference between the two groups.
“Our trial demonstrates that early treatment of mild-to-moderate COVID-19 with a triple combination of antiviral drugs may rapidly suppress the amount of virus in a patient’s body, relieve symptoms, and reduce the risk to healthcare workers by reducing the duration and quantity of viral shedding (when the virus is detectable and potentially transmissible).”
— Lead researcher Prof. Kwok-Yung Yuen, University of Hong Kong
“Furthermore, the treatment combination appeared safe and well-tolerated,” adds Prof. Yuen.
However, Prof. Yuen also warns that “despite these encouraging findings, we must confirm in larger phase III trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe illness (in whom the virus has had more time to replicate).”
Dr. Jenny Lo, from Ruttonjee Hospital in Hong Kong, echoes this sentiment. She says, “Interferon beta-1b may be a key component of the combination treatment and is worth further investigation for the treatment of COVID-19.”
“Interferons are naturally occurring proteins, produced in response to viral infection, and the hope is that interferon beta-1b will boost the body’s ability to fight SARS-CoV-2,” she adds. “Future phase III trials will soon confirm or refute the usefulness of this candidate drug as a backbone treatment for COVID-19.”
The study authors also highlight some limitations to their study. For example, they say that the open-label nature of the trial meant that both the researchers and the participants knew which treatment they were giving and receiving, respectively, and that there was no placebo group.
Still, Dr. Sarah Shalhoub — from Western University in Ontario, Canada — mentions the strengths of the trial a linked comment: “Most published studies so far have been retrospective or observational. Therefore, this prospective, randomized controlled design adds notable value to the growing evidence on treatments, eliminating a number of limitations inherent to retrospective studies.”
She adds, “This study presents a step toward finding a much-needed therapy for SARS-CoV-2. However, as the authors acknowledge, future studies to examine the efficacy of interferon beta-1b alone or in combination with other drugs to treat severe or critically ill patients with confirmed COVID-19 compared with placebo are warranted.”