UPDATE 5 June 2020
On 5 June 2020 the UK Recovery Trial withdrew hydroxychloroquine from its trial. In the wake of the ongoing controversy around the drug scientists reviewed the data on just over 1,500 patients who had received it and found it had no effect on the virus.
Original Piece 4 June 2020
The Solidarity Trial
There are currently in the region of 150 drugs being investigated as possible treatments for COVID-19. Most are drugs already in existence which are used for other conditions.
Of these, one of the most significant drug trials taking place is the WHO Solidarity Trial, a worldwide trial of four different treatment “arms”. It has so far recruited 3,500 patients from 35 different countries. (1)
The trial is looking at the following drugs:
Remdesivir
Hydroxychloroquine
Lopinavir with Ritonavir
Lopinavir with Ritonavir plus Interferon beta-1a.
Remdesivir
This anti-viral drug was first developed 10 years ago as a possible treatment for hepatitis C and then Ebola virus disease. However it failed in trials for both diseases. It has been shown to have some effect against both SARS and MERS, two other infections caused by viruses from the coronavirus family. (For more about SARS and MERS please click here)
It is given by injection into a vein and previous work with it has found it to be safe in humans.
It is being tested worldwide in severe cases of COVID-19 with results so far very mixed. One study in the US concluded it shortened illness length by four days but other trials have found no difference when it was tested against a placebo (an inert drug with no action.) (2) (3)
It has been authorized for emergency use in the US and Japan. On 26 May 2020 the UK authorised its use in some COVID-19 hospital patients, with doctors allowed discretion in selecting which patients receive it based on severity of illness. (4)
Hydroxychloroquine and Chloroquine
These anti-malarial drugs have received a lot of media coverage in recent weeks, not least when Donald Trump announced he was taking hydroxychloroquine to prevent COVID-19.
Hydroxychloroquine (but not chloroquine) was being researched as part of the WHO Solidarity Trial.
However on 22 May 2020, The Lancet medical journal published a study on both hydroxychloroquine and chloroquine that reported patients receiving the drug, either alone or in combination with a second drug, had a higher mortality rate than those not taking it. In particular, they were causing potentially fatal heart rhythm problems. (5)
Consequently, on 24 May 2020 the WHO paused the hydroxychloroquine arm within the Solidarity Trial while it analysed all the safety data.
Doubt has now been expressed in turn over the Lancet article and on the 3 June 2020 the WHO re-started the hydroxychloroquine arm of the trial. (6)
Lopinavir with Ritonavir
These two drugs are are a licensed treatment for HIV infection (Human Immunodeficiency Virus that causes AIDS.)
Initial studies in the laboratory suggested that they may have some effect against COVID-19 but when tested in people they did not reduce the number of deaths from COVID-19 or shorten the recovery time for survivors. (7)
However, these drugs have only been trialled in seriously ill patients so it is not possible to quantify their effects if given earlier in the illness.
Lopinavir with Ritonavir plus Interferon beta-1a.
Interferon is used to treat multiple sclerosis and is also involved in the body’s natural reaction against viral infection by boosting immunity.
Used in combination with Lopinavir and Ritonavir, initial studies showed that it shortened recovery time in people with mild to moderate COVID-19. (8)
The UK Recovery Trial
The largest drug trial in the world is taking place in the UK and is called the Recovery Trial.
It has recruited 11,000 patients from 175 different hospitals and is studying five different drugs:
Lopinavir-Ritonavir (as in the Solidarity Trial)
Low-dose Dexamethasone (a type of steroid which is used to reduce inflammation and swelling)
Hydroxychloroquine (see update of 5 June, now withdrawn from trial)
Azithromycin (A commonly used antibiotic. Although antibiotics do not kill viruses, only bacteria, azithromycin is unusual because it also modifies the body's immune reaction and has been shown to have some action against viruses through this effect)
Tocilizumab (an anti-inflammatory treatment given by injection that can also modify the body's immune reaction)
The Recovery Trial is also looking at the use of convalescent plasma, a blood constituent which is collected from people who have recovered from COVID-19. It contains antibodies against the virus which may help the patient fight the infection. (9)
Preliminary results from the Recovery Trial are not expected until early July but it has released a statement saying no adverse patient effects have yet occurred within the trial. (10)
In Conclusion
Overall, there is not yet a clear contender for a drug to treat COVID-19. It normally takes several years, sometimes up to 10 years, to develop a brand new drug which is why so many of the studies involve existing drugs. The UK Recovery Trial data may add extra information that will help establish a route forward in treating COVID-19. It is also possible that one of the many smaller trials, too numerous to discuss on this blog, will provide the "eureka moment" when a startling new discovery is made. What is clear is that every possible therapeutic option is currently being explored.
