19 Jun 2020, 08:45
- Dexamethasone has been hailed as a major breakthrough in Covid-19 treatment
- This comes after the world’s largest randomised clinical trial (RCT) of potential Covid-19 treatments
- Health24 spoke to experts on whether SA should start using dexamethasone for critically ill Covid-19 patients
Dexamethasone made headlines this week after it emerged that it was the only drug to have made a significant difference to patient mortality from Covid-19. The drug was part of the Randomised Evaluation of Covid-19 Therapy (RECOVERY) trial, a range of potential treatments tested for Covid-19 patients, Health24 reported.
But can we fully trust this drug hailed as a groundbreaking treatment? We spoke to Associate Professor Sean Wasserman, infectious diseases specialist at Groote Schuur Hospital, University of Cape Town; Dr Jantjie Taljaard, infectious diseases specialist at Tygerberg Hospital, Stellenbosch University; and Professor Francois Venter, director of Ezintsha, deputy executive director of Wits RHI, and member of the ministerial advisory committee (MAC).
Taljaard explains that the theoretical basis for this drug is the fact that it is a potent anti-inflammatory. The main problem in Covid-19 patients who deteriorate after a week or more of infection, is the severe inflammatory reaction that develops in response to the respiratory tract infection – also known as a “cytokine storm”. This complication is also well described in other viral respiratory tract infections like SARS and influenza, Taljaard adds.
“The cytokine storm, among other things, results in a condition called ARDS (acute respiratory distress syndrome), and other systemic complications including an increased tendency for clotting. So it makes sense that if one can avoid or suppress the cytokine storm with a potent anti-inflammatory, one may be able to attenuate the severe complications of Covid-19 and prevent mortality.”
Considering side effects for Covid-19 patients
Most drugs produce several side effects, and dexamethasone is no different. According to Wasserman, dexamethasone is a synthetic steroid drug that is widely used for many inflammatory conditions and certain cancers, and has well-established side effects with short term use, such as increased glucose and blood pressure. However, Wasserman says that these side effects are predictable and often not serious.
Venter supports this stance, saying that “the side effects of this course is probably relatively acceptable, as it is so short”.
However, Wasserman also said that the following should be considered: “Preliminary results from the RECOVERY trial reported the overall effect of dexamethasone on survival, but did not provide details about specific side effects when used for Covid pneumonia.”
Should we then use the trial results as definitive guidance?
The BBC reports that the UK government has 200 000 courses of the drug readily available and says the NHS will make the drug available to patients. Similarly, president Cyril Ramaphosa announced in his address to the nation last night that South Africa has “ample supply” of the drug and that the Department of Health and MAC has recommended that it be considered for use on patients on ventilators and oxygen.
However, the results of the RECOVERY trial have not yet been published in a journal. The website indicates: “Given the public health importance of these results, we are now working to publish the full details as soon as possible.”
Considering this, we asked experts whether the results should be treated with caution at this stage.
Wasserman said that the trial steering committee correctly decided to release these preliminary results, considering its public health importance: “RECOVERY is a well-designed randomised controlled trial with a publicly available protocol and transparent data collection processes.
“The large sample size and rigorous study design provide a lot of confidence in the preliminary finding that use of dexamethasone substantially improves survival in patients with Covid pneumonia who require oxygen,” Wasserman said, adding that while the full peer-reviewed publication is awaited as it will provide more details about the profile of trial participants and side effects of the drug, it is unlikely to alter the major findings of survival benefit that were announced this week.
‘Medical fraternity is cautiously optimistic’
Venter says that although the results have not yet been published, they’re likely to be positive: “They are a highly respected team, so we should start thinking hard about what to do if the peer-reviewed article shows the same.”
Taljaard also weighs in: “Although there is currently only a press release from the RECOVERY trial principal investigator, it shows very encouraging results. So the medical fraternity is cautiously optimistic and eagerly awaiting the publication of the complete data set and analysis,” and adds that a couple of things need to be considered, including weighing particular factors against the magnitude of benefit and making comparisons for different population groups, for example:
“Can the drug be recommended for all age groups, or do patients with obesity and diabetes benefit equally compared to patients with hypertension only? Were enough patients with HIV infection or tuberculosis included in the study to draw conclusions on the benefit versus risk for these populations?
“With the current information available to me, I do recommend that corticosteroid be given to patients with severe Covid-19 pneumonia, in particular those in need of high flow nasal oxygen or mechanical ventilation. Clinicians should also consider prescribing it for other patients in need of supplemental oxygen therapy who have a high risk of developing severe disease. This recommendation will have to be reviewed when more information becomes available.”
Should South Africa start using it for Covid-19 patients?
“If the peer-reviewed article bears out, absolutely,” says Venter. “There is not much in ICU that decreases death rates by 30%, sadly – so having this drug is certainly a step forward.”
Wasserman also commented that in the context of a public health emergency, and the fact that there is no other proven effective treatment for Covid pneumonia, these results should immediately translate into clinical practice and the drug should become the standard of care for this group of patients, further commenting:
“However, it will be important to carefully monitor the impact and safety of this approach in our population, which has a different socio-economic and disease profile to people in the UK where the RECOVERY trial took place. It is very important to understand that for now, the benefit of dexamethasone only applies to patients who were represented in the RECOVERY trial (i.e. hospitalised patients requiring oxygen) and not people with milder Covid-19.”
Although oral dexamethasone is currently not registered in South Africa, Wasserman says that equivalent doses of alternative steroid drugs may potentially be used. Business Insider reported that the regulated price per dexamethasone injection is between R149 and R176 in South Africa and is produced by pharmaceutical giant Aspen. According to its CEO Stephen Saad, who confirmed this to Business Insider SA, there should be sufficient supply to meet local demand.