Remdesivir, Hydroxychloroquine Ineffective in COVID-19 Management

Researchers aimed to establish new treatments for patients with COVID-19, but found no evidence of antiviral benefits or decreases in hospitalization and ventilation rates.

In the ever-changing clinical world of COVID-19, new treatment options for affected patients are always warranted. However, a recent Norwegian study found that remdesivir and hydroxychloroquine had no antiviral effect on hospitalized patients with COVID-19.

The study was prompted by the World Health Organization’s (WHO) request for the evaluation of 4 drugs approved for other indications, 2 of which were remdesivir and HCQ. An international, open-label, randomized clinical trial was conducted and compared to the standard of care (SoC) in the treatment of hospitalized patients with COVID-19, to varying degrees of success.

Along with a lopinavir group, the hydroxychloroquine group was dropped from the trial due to a lack of effect based on emerging external evidence from various trials, one of which being the RECOVERY (Randomized Evaluation of COVID-19 Therepay) trial.

Additionally, a WHO Solidarity trial showed that remdesivir showed little or no effect on in-hospital mortality and mechanical ventilation.

However, investigators considered the potential effects of both drugs, remdesivir especially, in the clinical course in patients to be “of major interest”, which prompted a NOR-Solidarity trial, and independent add-on study to the WHO-Solidarity trial.

The Study

Participants for the NOR-Solidarity study were recruited from 23 hospitals across Norway. Recruitment began on March 28, 2020, and ended on October 4, 2020.

In total, 181 patients were included in the full analysis set.

Eligible patients were 18 years or older with a confirmed infection of COVID-19. They were also required to be admitted to a hospital ward or intensive care unit with no anticipated transfer to a non-study hospital within 72 hours of inclusion.

Severe comorbid conditions with life expectancy of less than 3 months were considered key inclusion criteria.

The researchers, led by Andreas Barratt-Due, PhD, then allocated patients to the 3 groups using computer randomization procedures.

The 3 groups included local SoC, SoC plus 800 mg of oral hydroxychloroquine twice daily on day 1 and 400 mg twice daily up to 9 days, and SoC plus 200 mg of intravenous remdesivir on day 1, then 100 mg daily up to 9 days.

Systemic steroids for patients with severe and critical COVID-19 were added to the local SoC group in accordance with WHO guidelines on September 4, 2020.

Outcomes

After the trial, a total of 149 participated in 3 months of follow-up, while 32 patients were lost due to death (12), voluntary discontinuation (7), or other reasons such as emigration or underlying cancer (7). Only 6 patients left for unknown reasons.

The study showed that while in-hospital mortality in the study was lower than the overall mortality in the WHO Solidarity trial (6.6% as opposed to 11.8%), no differences in mortality, whether in-hospital, 28 days, or 60 days, were seen in the 3 groups.

Additionally, the investigators found no effects of remdesivir of hydroxychloroquine on ICE admission rates, mechanical ventilation, or time to receipt of mechanical ventilation. The duration of ICE stay and ventilation were also unchanged.

All patient groups had improved respiratory function during the first week of randomization, with the remdesivir group showing an increased improvement rate in the first 7 days.

Both drug groups also had significantly more rapid decreases in levels of ferritin in patients, as well as a decrease in dehydrogenase and procalcitonin (remdesivir and hydroxychloroquine, respectively) during the first week.

However, the study showed no marked or consistent effects on the inflammatory markers.

Researchers also acknowledge that in subgroup analysis, both remdesivir and hydroxychloroquine did not show any increased oropharyngeal viral clearance compared to SoC.

While Barratt-Due and colleagues hypothesized that the effect of both drugs could have been dependent on symptom duration prior to hospitalization, they conceded that the lack of antiviral effect was corroborated in previously published results from the WHO Solidarity study.

Similar findings in the recent trial led the team to question the antiviral potential of the drugs in hospitalized patients with COVID-19.

“Despite the early emergence of reports that both remdesivir and HCQ effectively exerted strong antiviral activities against SARS-CoV-2 in preclinical models, our results show no antiviral effects of these drugs in hospitalized patients,” the team wrote.

The study, “Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19,” was published online in the Annals of Internal Medicine.