What is the problem/background? We don’t know whether the addition of steroids (a class of medications that reduce the body’s reaction to injury or infection) to standard treatment in patients with pneumonia in Kenya is beneficial or not. Trials in patients with COVID-19 have shown that the addition of steroids reduces mortality. However, in Kenya most patients with pneumonia will not be tested for COVID-19 due to lack of resources. It is likely that clinicians in Kenya will treat all patients with pneumonia using steroids, in the belief that this strategy may be beneficial, based on data from preceding trials. This trial aims to determine whether such a strategy is beneficial to patients who are either negative for COVID-19 or their COVID-19 status is not known.

What questions are we trying to answer? In this randomized clinical trial, we would like to determine if the addition of steroids to the treatment regimen of patients with pneumonia in Kenyan hospitals is associated with reduced risk of death in the 30 days after admission to hospital. We will also study the perceptions of patients on the disease process and its treatment and determine if there are any specific biological features that influence the response to treatment in some patients.

Where is the study taking place, how many people does it involve and how are they selected? The study will take place at multiple health facilities in Kenya that participate in the Clinical Information Network (CIN), a collaboration that aims improve collection of inpatient information for use in improving care. The total number of patients will be 2,180 who will have been admitted to any of the participating hospitals with signs and symptoms of pneumonia. Patients who are willing and meet the criteria for entering the trial will be randomly assigned to either receive steroids in addition to their standard care, or standard care only.

What does the study involve for those who are in it? Adult patients admitted to hospital with a diagnosis of pneumonia, who are negative for COVID-19 or whose COVID-19 status is not yet known, will be eligible to participate. The attending clinicians will prescribe the standard antibiotics for pneumonia according to Kenyan clinical guidelines for all patients. The consenting process will take about 15-30 minutes. We will use a computer to randomly select approximately half of all the patients in the study, who will in addition to the antibiotics, also receive low-dose steroids. The duration of treatment with steroids will be for 10 days, in keeping with recent international trials. At the end of 30 days from entry into the study, we will make phone calls to all of the study participants in order to determine if there is a difference in the proportions of patients that are alive between the two study groups. In addition, ~100 randomly selected patients will also have their blood drawn at admission and after 24,48, and 72 hours of treatment for tests to examine factors associated with their response to the treatments.

What are the benefits and risks/costs of the study for those involved? 

There are no direct benefits to participating in the study. There is a benefit to society by helping us quickly find out if addition of steroids to treat patients with pneumonia is beneficial or not. Short term use of low-dose steroids is generally safe, but may lead to increased blood sugar in some patients. There might also be a small increased risk of other infections. Patients will be closely monitored for any complications and the study team will ensure that these are managed appropriately should they arise. For the ~100 participants who will have their blood drawn, this may be associated with slight pain and bruising which will resolve in a few days. There is also a small risk of local infection, which will be minimized by use of sterile equipment and trained clinical staff. The blood sampling will take an additional 15-30 minutes overall of the patient’s time, but this will be during the time that they are admitted to the ward. There are no costs to be incurred by patients participating in the study.

 How will the study benefit society?  The trial will help determine if steroids which are readily available in resource limited settings can be useful as an additional treatment for patients with pneumonia.

When does the study start and finish? The study will start upon receipt of ethical and regulatory clearance. Data collection, analysis and write up will take place over 12 months.

It is not known if adjunctive steroid therapy is beneficial in community-acquired pneumonia. Studies conducted elsewhere in the world have yielded conflicting results, and in those that suggested a benefit, this was limited to patients with severe disease. Dexamethasone was shown to be beneficial in patients with confirmed COVID-19 who had severe disease. The study showing benefit had most patients recruited in Europe. The WHO subsequently revised treatment guidelines to recommend the use of steroids in patients with severe COVID-19. COVID-19 testing remains low in low and middle-income countries such as Kenya; patients with acute respiratory signs and symptoms, possibly due to COVD-19 infection, do not always get tested. In the absence of routine testing for COVID-19, it is likely that clinicians will consider prescribing adjunctive steroids to patients with community-acquired pneumonia because of their proven benefit in patients with COVID-19. This open-label clinical trial will evaluate adjunctive low-dose steroids for treatment of adults admitted with pneumonia whose SARS-CoV-2 status is either unknown or negative, in order to determine if steroids are beneficial in our setting. We will also conduct immunology work in a subset of study participants to determine the correlation of pre-existing and treatment induced immune and metabolic changes with study outcomes.