This study finds evidence that corticosteroids can speed recovery and reduce the risk of death among hospitalized COVID-19 patients. However, these benefits are only found in patients who already need supplemental oxygen or ventilator support for breathing.
- In this randomized control trial, a cheap and common corticosteroid
(dexamethasone)reduced mortality and time spent in the hospital for patients who needed help breathing - either with supplemental oxygen or with a ventilator.
- Dexamethasone does not appear to help patients who don’t require oxygen or a ventilator, and may actually cause harm for these patients.
- These results indicate that use of corticosteroids should be considered for patients who have more severe symptoms from COVID-19.
Why is this important?
COVID-19 can have very high mortality rates for patients who have been hospitalized, and there are not many good treatments for patients who are doing poorly. In England, rates of mortality are as high as 37% in patients who need a ventilator to help them breathe. As a result, doctors have been looking at multiple possible treatments, including ones that have been seen in the news: vitamin D, hydroxychloroquine, remdesivir, and other medications. Among the treatments that have been tested in clinical trials, so far only remdesivir has demonstrated a reduction in the time for recovery, and it is not clear whether it reduces mortality from COVID-19. Even if remdesivir is an effective treatment, it remains fairly expensive and may not be widely available for all patients.
This particular study suggests that use of a commonly available corticosteroid, dexamethasone, may help to significantly reduce the risk of death or deterioration in the hospital, and improve the rate of recovery.
What did the study do?
Enrolled 6,425 patients across the UK
The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is a randomized control trial comparing multiple treatments for COVID-19 to standard hospital care in the United Kingdom, recruiting patients from 176 National Health Service hospitals.
Patients were eligible to join the trial if they had suspected or laboratory confirmed SARS-CoV2 infection, without medical history that might place them at risk for being part of the study. Pregnant and breast-feeding women were eligible. Initially patients had to be older than 18 years old, but this age limit was removed during the trial. Ultimately, 6,425 patients were included in this trial.
Researchers collected baseline data for patients: demographic information, other health conditions, and the level of respiratory support they needed (no support, oxygen, ventilation). They were then randomized to either receive standard hospital care (control), or to receive standard care plus dexamethasone, a corticosteroid (treatment).
Large diverse group of patients
Researchers did a good job of matching important factors that might affect how well patients would do: age, gender, need for respiratory support, and pre-existing health issues. However, they did not offer a specific breakdown of patient ages below 70 years, which means that there might be differences in the two groups.
Patients recieved other treatments too
The researchers point out that a number of patients received other treatments beyond steroids or standard care: azithromycin (24%), hydroxychloroquine (1%), and other treatments. However, they note that the number of patients receiving these treatments was very similar in control and treatment groups.
Unknown ethnic breakdown of patients
Researchers did not report patient ethnicity, so it is not clear whether these findings will apply across different ethnic groups.
Patients received standard care or standard care + dexamethasone
Patients were given either standard care in the hospital or were given dexamethasone (6 mg daily, for up to 10 days) in addition to standard care. Dexamethasone was given either as a pill or through an IV, and was administered “open label”. Open label randomization is where patients are randomized to a treatment that both patients and doctors are aware of.
By the end of the study, 95% of the treatment group and 7% of the control group received dexamethasone.
Not properly randomized
The randomization was done as an “open label” trial, meaning that both doctors and patients were aware of their treatment. This could have affected the results of the trial, as it might have generated a placebo effect for patients, and could have affected how patients were treated by their doctors. These factors could have affected their recovery in the hospital.
Compared mortality in dexamethasone group to control group
Researchers followed up with patients online at 28 days to determine whether they died, recovered, or were still in the hospital. They also determined other information, including whether they needed to move to the intensive care unit, whether they had to start using a ventilator, and whether they were discharged from the hospital.
These results were analyzed by an intention-to-treat analysis, which analyzes data from all patients assigned to the control and treatment arms, regardless of whether they received the treatment or not. Analyzing the results in this way helps researchers determine how effective an intervention (prescribing dexamethasone) is at treating a disease.
Researchers followed strict statistical approach
"Intention-to-treat" analysis is a stricter statistical approach. It includes patients who either drop out, or do not receive the intended treatment. This helps to preserve the randomization of patients and avoid possible factors that could bias the results of the study.
Limited follow up
Follow up was limited to 28 days after inclusion in the trial. Understanding the longer term effects of this treatment on both hospitalized patients and patients who leave the hospital will be important in evaluating corticosteroids as a therapy for COVID-19.
Dexamethasone can help patients who already need respiratory support
The researchers found that overall, giving hospitalized patients corticosteroids significantly reduced the rate of death due to COVID-19 (21.6% vs 24.6% mortality). As a further analysis, researchers examined which kinds of patients benefited the most from corticosteroids. They divided patients into three categories:
- those who did not require any assistance breathing
- those who required supplemental oxygen
- those who required ventilator support
They found that patients who had more severe disease (requiring oxygen or ventilator) had statistically significant benefit with corticosteroids:
- patients requiring oxygen - 20% reduction
- patients requiring ventilator - 35% reduction
However, patients with mild symptoms did not show any benefit, and may have actually done worse, though this was not statistically significant (20% increase in mortality).
When looking at other outcomes, the researchers found that corticosteroids were associated with a statistically significant reduced hospital stay (12 vs 13 days) and a statistically significant decrease in the risk of needing to be put on a ventilator (14% reduction).
Statistics for study were well planned
The researchers performed a power analysis to guide the size of their study population. We do note that the original power calculation was performed for a larger effect size (4% decrease in mortality), but the results of the study are fairly close to the predicted effect size, so the study is still well designed.