Remdesivir Shows Promise for Helping COVID-19 Patients Recover More Quickly
Preliminary results of a clinical trial have provided some hope for an effective treatment to reduce severity of COVID-19. Federal health officials announced results of a study, involving more than 1,000 patients, that indicates quicker recovery for patients receiving the antiviral remdesivir than a placebo. Here is more information.
BETHESDA, MD – The antiviral remdesivir is showing promise as an effective treatment for COVID-19.
Preliminary data analysis from a recent randomized controlled trial indicates that patients hospitalized for advanced novel coronavirus infection and lung involvement recovered more quickly when they received remdesivir than when they were treated with a placebo, according to a government press release.
The National Institute of Allergy and Infectious Diseases-sponsored study involved 1,063 patients and began on Feb. 21, 2020. It is the first clinical trial launched in the United States to evaluate an experimental treatment for COVID-19.
Based on the review of an independent data and safety monitoring board (DSMB) overseeing the trial – which met on April 27 to review data and shared their interim analysis with the study team -- remdesivir was deemed better than placebo for the primary endpoint. That was time to recovery, defined as being well enough for hospital discharge or returning to normal activity level.
In fact, preliminary results found that patients who received remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001). Patients treated with remdesivir had a median time to recovery of 11 days vs. 15 days for those who received placebo.
A survival benefit also was suggested, with a mortality rate calculated at 8.0% for the group receiving remdesivir compared to 11.6% for the placebo group (p=0.059). A yet-to-be released report will provide more details, according to NAIAD, which is part of the National Institutes of Health.
Meanwhile, in an effort to expedite the development and availability of potential COVID-19 treatments, the Food and Drug Administration has been discussing with remdesivir’s maker, Gilead Sciences Inc., how to make the drug available for use in patients as quickly as possible, as appropriate. Remdesivir is an investigational broad-spectrum antiviral treatment administered via daily infusion for 10 days.
While the initial trial was closed to new enrollments on April 19, NIAID is discussing how to move forward with the research, possibly looking at the incorporation of additional investigative treatments. The agency’s director, Anthony Fauci, MD, said at a White House press conference that one possibility was testing the administration of remdesivir with some type of anti-inflammatory.
NAIAD said the first participant in the ACTT trial was an American who was repatriated after being quarantined on the Diamond Princess cruise ship that docked in Yokohama, Japan, and volunteered to participate in the study at the first study site, the University of Nebraska Medical Center/Nebraska Medicine, in February 2020. Ultimately, 68 sites were part of the study -- 47 in the United States and 21 in countries in Europe and Asia.
Remdesivir also has shown hopeful signs in animal studies. NIH announced results of a preliminary trial showing that early treatment with the antiviral significantly reduced clinical disease and damage to the lungs of rhesus macaques infected with SARS-CoV-2, the coronavirus that causes COVID-19.
What Medications Are Okay for Continued Use by Patients With COVID-19?
With so many different reports – from specialty societies and others – about which drugs are acceptable or dangerous for novel coronavirus patients to use, pharmacists and other healthcare professionals are likely to be confused. Find out how new treatment guidelines from the National Institutes of Health can help, by evaluating and pulling together all of the information.
NEW YORK – What medications are okay to continue to use for patients with COVID-19 and which should be discontinued?
Those were among the questions answered by a panel of U.S. physicians, statisticians, and other experts who developed treatment guidelines for coronavirus disease 2019 (COVID-19).
The guidelines for healthcare provider are based on published and preliminary data and the clinical expertise of the panelists, many of whom are frontline clinicians caring for patients during the pandemic. Panel co-chairs -- Roy M. Gulick, MD, chief of the Infectious Disease Division at Weill Medical Hospital of Cornell University in New York, and Clifford Lane, MD, clinical director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health and Henry Masur, MD, chief of the Critical Care Medicine Department at the NIH Clinical Center, say the guidance will be updated with the availability of new data.
The guidelines provide some clarity where a great deal of confusion has been created. For example, despite earlier controversy, the panel recommends that COVID-19 patients prescribed angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for cardiovascular disease (or other indications) should continue the medications.
“Angiotensin-converting enzyme 2 (ACE2) is the cell surface receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),” according to the document. “It has been hypothesized1 that the modulation of ACE2 associated with these therapies could suppress or enhance SARS-CoV-2 replication. Investigations of the role of ARBs and recombinant human ACE2 in treatment and prevention of SARS-CoV-2 infection are underway.” At this point, however, the panel says, “Whether these medications are helpful, harmful, or neutral in the pathogenesis of SARS-CoV-2 infection is unclear. Currently, there is a lack of sufficient clinical evidence demonstrating that ACE inhibitors or ARBs have any impact on the susceptibility of individuals to SARS-CoV-2 or on the severity or outcomes of infection.”
Recommendations on use of systemic corticosteroids are more mixed, however. The panel recommends that oral corticosteroid therapy used prior to COVID-19 diagnosis for another underlying condition, such as primary or secondary adrenal insufficiency or rheumatological diseases, should not be discontinued and suggests that supplemental or stress-dose steroids might be required on a case-by-case basis.
No discontinuation is recommended for inhaled corticosteroids used daily for patients with asthma and chronic obstructive pulmonary disease for control of airway inflammation, according to the document, which notes, “No studies to date have investigated the relationship between inhaled corticosteroids in these settings and virus acquisition, severity of illness, or viral transmission.”
When it comes to more severely ill patients, the recommendations on corticosteroid therapy are more complex, with the authors emphasizing that the medications can affect the pathogenesis of viral infections in several ways. They point out that, in outbreaks of other novel coronavirus infections such as Middle East respiratory syndrome [MERS] and severe acute respiratory syndrome [SARS]), corticosteroid therapy was associated with delayed virus clearance. The concern is that corticosteroid therapy could worsen clinical outcomes, including secondary bacterial infection and mortality.
“Conversely, the potent anti-inflammatory effects of corticosteroids are proposed to have a potential therapeutic role in suppressing cytokine-related lung injury,” the document notes. “Data on the use of corticosteroids in COVID-19 are limited. The recommendations for use of corticosteroids in patients with COVID-19 depend on the severity of illness, indication, and underlying medical conditions and should be considered on a case-by-case basis.”
The authors also recommend against the routine use of systemic corticosteroids for the treatment of COVID-19 in hospitalized patients unless they are in the intensive care unit. Some guidelines outside of the United States have proposed the use of low-dose, short-course corticosteroids in patients with progressive deterioration of oxygenation or elevated inflammatory markers, but the guidelines urge clinicians to use the drugs cautiously, weighing risks and benefits.
If infected with COVID-19, patients prescribed statin therapy for the treatment or prevention of cardiovascular disease should continue their medications, the guidelines states, although not enough data is available to recommend the drugs for treatment of COVID-19. “Observational studies have reported that statin therapy may reduce cardiovascular morbidity in patients admitted with other respiratory infections, such as influenza and bacterial pneumonia,” the authors write.
The guidelines also reject warnings against nonsteroidal anti-inflammatory drugs (NSAIDs), advising that patients using them for a co-morbid condition should continue therapy as previously directed by their physician. In fact, the panel proposes that “there be no difference in the strategy of antipyretic use (e.g., with acetaminophen or NSAIDs) as in patients with or without COVID-19.”
Background information explains that in mid-March 2020, “news agencies promoted reports that anti-inflammatory drugs may worsen COVID-19. It has been proposed that NSAIDs like ibuprofen can increase the expression of ACE21 and inhibit antibody production.Shortly after these reports, the Food and Drug Administration stated that there is no evidence linking the use of NSAIDs with worsening of COVID-19 and advised patients to use NSAIDs as directed.”